ITPD20110227A1 - HEMOSTATIC AGENT PARTICULARLY FOR USE IN SURGICAL OPERATIONS - Google Patents

Description

HEMOSTATIC AGENT ESPECIALLY FOR USE IN SURGICAL INTERVENTIONS

DESCRIPTION

The present invention relates to a hemostatic agent particularly for use in surgical interventions.

The invention is placed between the products, and the consequent techniques, which contribute to minimizing blood losses during surgical interventions, for example liver resection, and is aimed both at parenchymal transection and at the simultaneous coagulation of the section slice.

Reducing blood loss and consequently of blood and blood products, is one of the development targets of surgery in general.

The reasons are related to the risk of transfusion, high costs and religious reasons.

We recall that by haemostasis we mean the arrest of both arterial and venous bleeding.

Hemostasis can occur spontaneously thanks to the coagulation phenomenon or be mechanically induced as happens in surgery where it represents a decisive part of the operation.

There are many known techniques, which help to minimize blood loss during surgery, such as liver resection or similar interventions on other organs, and the most common are listed below.

Pre-operative preventive hemostasis.

Performed before the operation, it aims to reduce or stop the blood flow in a specific district by affixing laces or bandages. It serves to make the operating field bloodless and is used above all in orthopedics in limb interventions.

The problem is that it is to be considered transitory as the method cannot be continued beyond 30-45 minutes from which to avoid problems of ischemia in some structures.

Temporary intra-operative preventive haemostasis. Used above all in vascular surgery, it consists in stopping the flow of blood by compressing the distal and proximal portion of the vessel with respect to the segment on which it is necessary to intervene with special ties or forceps called angiostats. At the end of the intervention time, the laces or angiostats must be removed.

Definitive intra-operative preventive haemostasis. It represents the first, fundamental moment of demolition surgery. The structure to be removed is deprived of the blood supply by seeking and blocking the afferent vessels. These vessels will be dissected after having closed them between two laces or between two hemostatic forceps. This will help to significantly decrease the blood flow but almost never stop it completely due to the large number of vascular afferents present in almost all organs, often so numerous and small as to make preventive haemostasis laborious and superfluous.

It is possible to obtain haemostasis not only with the methods described but also by resorting to other methods or tools.

Normally the system deemed most suitable for the circumstance is used and the one that offers the best guarantees of tightness over time.

The aim is to avert one of the most fearful complications of surgical interventions, namely post-operative bleeding.

The haemorrhage can be localized or diffuse to nappo, internal or external, profuse or modest and can originate from arteries, veins or capillaries; in any case it always constitutes a serious threat to the patient's ability to counterbalance the reduction in volume of circulating blood. If left unchecked, it can cause hypovolemic shock, hypoxia with multi-organ failure, or cardiac arrhythmias.

Prevention and control of bleeding are of vital importance in surgery and the available supports play an essential role in surgical haemostasis, however, the experience of the operator is also important in order to optimize the use of various mechanical, thermal or chemical systems.

Although scientific discoveries offer more and more valid technological supports to reduce blood loss during surgery, the basic principles of the surgical technique remain imperative.

The systems available for achieving haemostasis are very varied and depend on where it is needed.

In general, the supports for surgical haemostasis are classified into:

External mechanical systems:

1. tourniquets;

2. compression dressings;

3. patches or gauze soaked in hot physiological solution kept for a few minutes on large bloody surfaces and which show diffuse bleeding that cannot be otherwise controlled;

4. manual or digital compression

Internal mechanical systems:

1. manual or direct digital compression 2. hemostatic forceps

3. clip ligation suture

4. vascular control (clamp torniquet laces) 5. endostapler

6. Cusa ultrasound dissector

7. compressions

8. Absorbable jellies

9. Oxidized regenerated cellulose.

Thermal systems

1. Monopolar or bipolar device

2. Argon Beam plasma-ion electrocoagulator

3. Harmonic scalpel

4. Tissue Link Floating Ball

5. Ligasure vessel sealing system

All these methods are able to stop bleeding because they cause the denaturation of collagen due to the high temperatures they generate, they are effective methods which however have the disadvantage of being able to lead to permanent lesions of the treated tissue.

Chemical agents

1. Collagen

2. Fibrin based glue

3. Thrombin

4. Cyanoacrylate based glue

5. Alcohol

Reducing blood loss and consequently blood and blood products is a further aim of surgery in general.

The reasons are linked to: transfusion risk, high costs and religious reasons.

Transfusion risk.

Most transfusion complications are related to administration errors, ie blood transfused incorrectly due to unidentified incompatibility or personal error.

Adverse events after transfusion can be: infectious, from immunological reaction, from immunosuppression.

Infectious complications are linked to the transmission of viral, bacterial, parasitic agents, prions, etc.

High costs.

The collection, storage and handling of blood and blood products has a cost, in relation to the material used and the human work performed.

The enormous demand for blood and blood products by today's health care is an important item of expenditure, which contributes to the chronic liabilities of healthcare companies.

There are also problems related to religious reasons (Jehovah's Witnesses).

In addition to this, a very frequent problem in surgery is represented by the haemostasis of large areas in which the bleeding is not determined by a single vessel, but by many small vascular mouths, as for example in the areas of spit of the pelvic excavation. , or, even worse from the point of view of difficulty, in trances, that is, in the sections of parenchymatous organs, such as: liver, kidney, and pancreas. At this level it is necessary to proceed with more sophisticated haemostasis methods, represented by the use of electrosurgical units and biological glues.

The use of the electrosurgical unit, during the hepatic resection surgery, is aimed both at the parenchymal transection and at the simultaneous coagulation of the section slice.

To better facilitate this last process, the addition of drops of water is associated during the action of the electrosurgical unit.

In this way the heat developed by the scalpel causes the evaporation of the water with a consequent increase in the diffusion of heat through the parenchymatous tissues and denaturation of the collagen with consequent haemostatic action. The use of water is also able to reduce the adhesion of the blade of the electric scalpel to the parenchymatous tissue due to the excessive temperature in the limited area of application.

However, this method has the disadvantage that it can lead to permanent lesions of the treated tissue.

Another current approach to the control of haemostasis in so-called â € œa tasselâ € bleeding, ie entire surfaces that ooze blood, is the use of glues.

In clinical practice in recent years the use of synthetic glues has been consolidated, for example based on derivatives of cyanacrylate, and of glues identified with the term biological glues.

Their use is selectively tested in relation to the anatomical and anatomic functional conditions to be treated. The biological glue has had a somewhat more widespread application in recent times as a reinforcement and protection of intestinal and pancreatic anastomoses, and are also used, with great effectiveness, to favor the haemostasis of the trance sections, after the resection of parts of parenchymatous viscera, such as liver and kidney. They carry out their haemostatic action by intervening on the secondary haemostasis processes characterized by the stabilization of the platelet aggregate mediated by the activation of fibrin. They also represent systems that are very well tolerated by the organism, however, due to their activity, they lend themselves above all to being used as reinforcement and protection of anastomoses and as haemostats in the case of resections of parenchymatous organs in which the main vessels have been previously clamped.

The general purpose of the present invention is to provide a hemostatic agent which allows to overcome the problems associated with known methods of intervention.

The main object of the present invention is to reduce blood loss and consequently blood and blood derivatives in surgery in general with a hemostatic agent.

A second aim is to consequently reduce the transfusion risk.

A further purpose is to eliminate the problems related to religious reasons.

Not least purpose is to reduce costs.

The proposed and still high aims which will appear more clearly later are achieved with a

Hemostatic agent particularly for use in surgical interventions, characterized in that it comprises in aqueous solution at least:

an aluminum salt from 5 to 30% by weight;

an iron salt from 1 to 30% by weight;

Methylcellulose from 0.1 to 8% by weight.

APPLICATION EXAMPLE

In light of the foregoing, in an operation with electrosurgery, the water was initially replaced with a hyperosmotic solution in order to facilitate dehydration of the tissues along the section slice and consequently reduce its bleeding.

For this purpose, the haemostatic, dehydrating and cauterizing activity of some solutions with substitute or adjuvant action to the electric scalpel was evaluated, reopening the possibility of intervening in the treatment of haemostasis with a greater range of surgical techniques.

All the selected salts are characterized by being soluble in water and leading to the formation of aqueous solutions at acidic pH.

They were selected for their coagulating activity linked to an interaction with secondary haemostasis processes and for their cauterizing activity.

The experiments developed were divided into two parts:

1) in vivo experiments on a simple animal model: the rat

2) in vivo experiments on a complex animal model: the pig.

In the light of the results obtained with the tests on rats, experiments were carried out operating on pigs.

The experiments were conducted keeping the animals anesthetized with nitrous oxide 28-29%, O270% sevorane 1-2% and esmeron 50 mg as needed.

After median abdominal incision, the hepatic anchors to the abdominal cavity were freed and the pig liver parenchyma was subsequently interrupted by surgical scissors.

The bleeding resulting from the clean cut of the scissors was answered by depositing the following solution in the slice of the dissected hepatic lobe with reference to a total of 100%:

Aluminum Chloride hexahydrate (Al Cl3 <.> 6 H2O) 20% Iron Chloride (Ferric chloride Fe <+++>

Cl3) 6% Methylcellulose 0.9%

H2O 73.1%,

observing the effective or not coagulating action of the same.

The tested solution demonstrated a coagulating, cauterizing and dehydrating activity along the hepatic section treated. In order to quantify the tissue damage, the resection margin was subjected to histological examination. The experiments carried out have currently made it possible to select the optimal formulation containing 6% of Iron Chloride (Ferric chloride Fe <+++>

Cl3) with coagulating action, 20% of Aluminum Chloride hexahydrate (Al Cl3 <.> 6 H2O) with cauterizing action and 0.9% of Methylcellulose as a viscosifying agent.

The results obtained are evidenced by the histological report which confirms that the tissue damage caused by the formulation is significantly lower than that caused by the normal conditions of use of the electric scalpel, both in terms of parenchymal extension and in terms of necrosis from tissue damage.

The collected evidence testifies to the ability of the solution to lead to a controlled hemostasis of the parenchymatous tissues, respecting the vascular structures and allowing, thanks to the fluidity of the solution, to penetrate three-dimensionally along the section slice allowing the hemostasis of the tissues underlying the vascular structures , inaccessible to cauterization with an electric scalpel.

In favor of the formulated solution, the economic aspect is of crucial importance; an approximate count allows us to hypothesize that the quantity of solution necessary to face a major liver resection surgery is about 20 g of solution, with a corresponding extremely low cost.

From what has been described and illustrated, it can be seen that the proposed purposes have been achieved in an effective and advantageous way.

Claims (7)

CLAIMS 1) Hemostatic agent particularly for use in surgical interventions, characterized in that it comprises in aqueous solution at least: an aluminum salt from 5 to 30% by weight; an iron salt from 1 to 30% by weight; Methylcellulose from 0.1 to 8% by weight. 2) Hemostatic agent as in claim 1 characterized in that the aluminum salt is Aluminum Chloride hexahydrate (Al Cl3 <.> 6 H2O). 3) Hemostatic agent as per claim 1 characterized in that the iron salt is <+> Iron Chloride (Ferric Chloride Fe <++> Cl3). 4) Hemostatic agent as per claims 1 and 2 characterized in that the Aluminum Chloride hexahydrate (Al Cl3 <.> 6 H2O) is in a percentage of 20% by weight. 5) Hemostatic agent as per claims 1 and 3 characterized in that Iron <+++> Chloride (Ferric Chloride Fe Cl3) is a percentage of 6% by weight. 6) Hemostatic agent as claimed in claim 1, characterized in that the methylcellulose is in a percentage of 0.9% by weight. 7) Hemostatic agent as in claim 1, characterized in that it has the following formulation referred to a total solution of 100%: Aluminum Chloride hexahydrate (Al Cl3 <.> 6 H2O) 20% Iron Chloride (Ferric chloride Fe <+++> Cl3) 6% Methylcellulose 0.9% H2O 73.1%.