RU2796161C1 - Hemostatic gel for single topical application - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: single-use hemostatic gel is disclosed, consisting of a high-molecular sodium compound carboxymethylcellulose (Na CMC), the active ingredients of which are calcium chloride (CaCl₂) and 6-aminocaproic acid (6-ACC), while 1,000 g of the gel contains 40 g of CaCl₂, 50 g of 6-AKK, 60 g of Na CMC, and 850 ml of purified water.

EFFECT: invention provides an increase in the hemostatic effect and a decrease in the time of onset of a complete stop of bleeding.

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Description

The field of technology to which the invention belongs

Single topical gel is designed to stop bleeding of varying intensity, when providing for both first aid and first aid, emergency medical and primary health care, in the field and at home, in combat areas, as well as in a hospital to stop bleeding associated with vascular damage, including from parenchymal organs, by activating the human hemostasis system. The gel is intended for local (external) use only.

State of the art

At the turn of the XX-XXI centuries. the spectrum and nature of threats to the security of an individual, society, and the state have changed; new approaches to risk assessment in the main areas of human life have been identified. Significant progress has been made in the theory and practice of ensuring safety in emergency situations of a natural, man-made, social and environmental nature.

Medical protection is one of the important elements of the medical support system: it is aimed at preserving the life, health and capacity of people under the influence of damaging factors of radiation, chemical and biological nature. Medical protection is a complex of special sanitary and hygienic, preventive and therapeutic measures taken to prevent or weaken the effect of OHTV, ionizing radiation and biological agents, as well as to save life, restore health and professional performance of affected people.

Based on GOST R 22.3.11-2016 “Safety in emergency situations. Means of protection medical. Classification” medical protective equipment (MSZ) includes medicines, materials, special equipment, medical devices, kits, kits, first-aid kits and packing from these funds, intended for medical protection measures, first aid (in the order of self- and mutual assistance) , primary health care at the scene, in emergency situations (in the focus of the lesion, the zone of contamination, infection) and at the stages of evacuation in order to prevent damage or reduce the effect of exposure to damaging factors and prevent complications of lesions.

According to the nature of their use, incinerators are divided into prophylactic drugs and emergency medicines. Prophylactic drugs are used in advance, before the onset of exposure to damaging factors, and should have minimal side effects. Means of emergency medical care are used after exposure to a damaging factor and should minimize possible negative consequences as much as possible.

Medical personal protective equipment does not have universality when exposed to various damaging factors on the human body. In each specific case, a remedy is sought that, when introduced into the body, could either weaken or prevent a violation of its function under the influence of a damaging factor. Their introduction into practice and use is possible only after a thorough study of the effectiveness of protective agents and undesirable side effects on the body, an assessment of the appropriateness of use.

Improvement of MSZ is aimed at fulfilling a number of the following requirements to improve the effectiveness of their protective properties:

- the possibility of taking medicines in advance and before the onset of exposure to damaging factors;

- ease of use of drugs and the possibility of their long-term storage;

- sufficient effectiveness of the protective properties of drugs with the exception of possible complications in their use;

- economic feasibility of using medicines in terms of their effectiveness, shelf life, subsequent use in healthcare practice when refreshing stocks, and the possibility of production.

Hemostatics (local hemostatic agents) are biosurgical materials that have a hemostatic effect in direct contact with damaged body tissues. Designed to provide medical care to victims in emergency situations directly in the lesion, emergency zone, at the collection point for victims, as well as in a vehicle during medical evacuation. This group includes a wide range of drugs with different mechanisms of action.

Hemostatic agents of local action are in the form of sponges, gels, powders, waxes, glue.

Due to the combined composition of the hemostatic gel, two actions are simultaneously provided: the launch of a cascade of thrombus formation and the disruption of the functioning of the blood thrombolytic system. The gel, spreading over the wound, quickly forms a structured dense film of a regular spatially directed structure, which provides strong coagulation of damaged vessel walls. Thus, it prevents secondary infection of the wound, provides optimal conditions for wound regeneration and postoperative epithelialization of the wound surface, followed by the formation of granulation tissue.

Currently used hemostatic agents based on zeolites, chitosan, and other materials have their own limitations for use. So, for example, a group of powder MGS - zeolite, chitosan (QuikClot, QuikClotACS +, HemСon, Combat Gauze Celox).

The drug - QuickClot based on mineral rocks (derivatives of zeolite), when applied to the wound, releases a large amount of heat. As a result, bleeding stops not due to clotting, but due to “cauterization”, which brings severe pain and burns to the victim. The domestic drug GEMOSTOP - copied by QuickClot, is dangerous to use due to the potential for severe burns.

The more advanced Celox preparation contains the natural polysaccharide chitosan. The hemostatic effect is achieved by binding positively charged particles of Celox to negatively charged erythrocytes, by mixing and "gluing" them together, thus forming a "pseudo clot". This clot sticks well to wet places, allowing you to literally plug the wound surface. Such an approach is potentially dangerous due to the possibility of thrombosis due to the drug getting into the circulatory system, in addition, there is a problem of extracting the pseudoclot from the wound after the evacuation of the victim. There is also an insufficient hemostatic effect and weak adhesive ability when using products based on chitosan powder or granules. The disadvantages of this group of drugs are the short duration of action, low specific activity and the existing potential for infection of the wound in the "field".

The listed powder hemostatics show weak adhesive properties to the entire surface of the wound, which makes it impossible to stop heavy bleeding from deep wounds without additional strong mechanical tamponade and does not exclude the possibility of repeated heavy bleeding. Field use of this group of MHSs often leads to septic complications. With intensive bleeding, to achieve stable hemostasis of the wound, a significant amount of powder or bandage hemostatic agent is required. As a result, with severe bleeding, these funds, not having time to have a hemostatic effect, are partially washed off from the bleeding surface.

It is difficult to work with hemostatic agents in powder form under extreme conditions: the powder is blown away by the wind, wakes up past the wound, and becomes contaminated.

When used in the field, the above remedies are ineffective in severe bleeding at the prehospital stage.

In addition, analogues demonstrate a longer time (up to 3 minutes) for the onset of a complete stop of bleeding (an important factor for military field medicine and disaster medicine). The form in the form of a gel of various densities is convenient for stopping bleeding from wounds of complex configuration and various depths. This distinguishes the drug from the main type of hemostatic agents in the form of powder (Celox) and non-woven materials in the form of a bandage (Hemoflex) based on chitosan. It is also possible to note the difficulty of using the used powder hemostasis systems (for example, in case of wind), and the need to apply efforts in the form of additional tamponade.

The technical problem solved by the claimed invention is to increase efficiency.

The technical result is to increase the hemostatic effect and to reduce the time of onset of a complete stop of bleeding.

The specified technical result is achieved in a single topical hemostatic gel, which consists of a high molecular weight sodium compound carboxymethylcellulose (Na CMC), the active ingredients of which are calcium chloride (CaCl ₂ ) and 6-aminocaproic acid (6-ACC), while 1000 g of the gel contains : CaCl ₂ - 40 g, 6-AKK - 50 g, Na CMC - 60 g, purified water - 850 ml.

An additional feature is that Na CMC is mixed evenly, in parts, to distribute the active ingredients throughout the finished product.

The principle of action of the constituent components of the gel is implemented by physical and chemical effects on the wound surface.

1. The main component of the gel - compounds of calcium salts are used as clotting activators. Calcium salts are an essential participant in the formation of a fibrin clot. Due to this, a dense clot is formed, which coagulates the vessel at the site of injury, which provides a hemostatic effect.

2. An additional coagulation activator is 6-aminocaproic acid, an inhibitor of fibrinolysis that interferes with the process of the natural anticoagulant system of the human body.

These chemicals that are part of the medical device do not have a systemic pharmacological effect and perform a physical hemostatic function due to the surface-active properties of the gel, which activates the natural human hemostasis system, which helps protect damaged skin from mechanical and chemical irritants. And provide the possibility of its use in accordance with the intended purpose.

Mechanism of action

1. Due to the polymer components, the gel provides local hemostasis by sealing and accelerating blood clotting. The gel is a hemostatic agent of mixed action, combining the effects of stimulation of the coagulation and inactivation of the anticoagulant systems of the blood. Acting as a protein coagulant, the salt compounds in the gel ensure the formation of a blood clot and prevent re-bleeding.

2. The mechanism of the hemostatic action of the gel is based on the absorption of the liquid component of the blood, which leads to the concentration of coagulation factors and platelets on the surface of the wound. In fact, the calcium salt compounds in the gel react with blood proteins, physically causing the proteins to coagulate. An additional component - a derivative of the amino acid lysine (6-ACC) prevents the destruction of the formed fibrin clot.

3. The gel forms a sealed insulating layer until it is removed. Due to this form, the content is not washed off from the damaged area, easily clogs the area and penetrates into the damaged tissues.

Thus, two stages can be distinguished in the mechanism of action of a hemostatic agent: the first is the natural formation of a clot, the second is the inhibition of the processes leading to its resorption. The principle of action described above indicates that the product exerts its hemostatic effect due to the mechanical obstruction of bleeding - the physical method of hemostasis.

Compared to known analogues, the hemostatic gel according to the present adheres gently to a wet surface and is not pushed out by the blood, unlike liquid hemostatics.

The physical properties of the structure in the form of a hemostatic gel are convenient when providing first aid. It provides isolation of the damaged surface, prevention of infection, complete atraumaticity, and can be used as an alternative to the unsafe tourniquet procedure (especially for injuries of the proximal segments of the extremities, neck and pelvis).

Hemostatic is universal and suitable for stopping bleeding from wounds of any type (even penetrating ones), from large superficial and deep wounds and cuts. The use of hemostatic does not require special training and does not cause difficulties. In terms of the totality and degree of therapeutic effect on the wound, it has no direct analogue.

Application procedure. Before applying the gel, it is recommended to clean the wound as much as possible from foreign bodies, blood clots to ensure maximum contact of the gel with the damaged vessel. If the arteries are damaged before using the gel, it is advisable to temporarily stop the bleeding by pressing the damaged artery with a finger or applying a hemostatic tourniquet to prevent the drug from being washed out of the wound by a blood stream. The gel is applied by infusion / extrusion into the wound directly to the source of bleeding. After filling the wound cavity over the gel, it is necessary to apply a cotton-gauze swab or bandage, folded in several layers, and perform manual compression for 3-5 minutes. After that, in case of stopping the bleeding, the tampon must be fixed (a pressure bandage is applied). In case of ineffective hemostasis, repeated infusion / extrusion of the gel and compression for 5-7 minutes are indicated. Infusion / extrusion of the gel is carried out from the following package. If bleeding continues after this, a tourniquet should be applied. It is advisable to immobilize the injured limb to reduce the risk of rebleeding.

The manufacturing process of 1000 g of gel requires 850 ml of purified water, 40 g of CaCl2, 50 g of 6-ACC and 60 g of Na CMC. The preparation of the gel is carried out as follows. 850 ml of purified water is introduced into the reactor for the manufacture of the gel. With stirring, 40 g of anhydrous CaCl2 are added to the reactor and heated to 40°C. The process of dissolution of the calcium salt is accompanied by the release of energy, which reduces energy consumption for heating.

After complete dissolution of CaCl2, 50 g of 6-ACC are added to the solution and dissolved until a clear solution is obtained.

The process of gel formation requires a step-by-step uniform mixing of Na CMC into the solution for the distribution of active substances over the finished product, which is carried out as follows. When the stirring is stopped, 10 g of gelling agent (Na CMC) is distributed on the surface of the solution in a uniform layer. The system (reactor) is sealed and air is pumped out using an oil or membrane type vacuum pump.

After swelling and partial dissolution of the gelling agent, stirring is turned on and it is continued until a visually evenly distributed gel is obtained. The procedure is repeated until a total of 60 g of gelling agent is added. It is critically important to observe the correct process of swelling of the gelling agent. Dense lumps of gelling agent that has not undergone swelling can be rubbed against the walls of the reactor with a spatula.

Vacuumization of the reaction mixture is necessary to avoid interfering with the gel of a huge amount of air. After obtaining a gel of uniform viscosity, it should be stored in sealed packaging.

Claims (6)

1. A single-use hemostatic gel consisting of a high-molecular sodium compound carboxymethylcellulose (Na CMC), the active ingredients of which are calcium chloride (CaCl ₂ ) and 6-aminocaproic acid (6-ACC), while 1000 g of the gel contains: CaCl ₂ - 40 g, 6-ACC - 50 g, Na CMC - 60 g, purified water - 850 ml. 2. Hemostatic gel according to claim 1, characterized in that Na CMC is mixed evenly, in parts, to distribute the active ingredients throughout the finished product.