Patent Publication Number: US-2022226370-A1

Title: Glycerol and sodium pentaborate based formulation preventing postoperative adhesions

Description:
CROSS REFERENCE TO THE RELATED APPLICATIONS 
     This application is the national stage entry of International Application No. PCT/TR2020/050466, filed on May 29, 2020, which is based upon and claims priority to Turkish Patent Application No. 2019/08285, filed on May 30, 2019, the entire contents of which are incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present invention relates to a glycerol and sodium pentaborate based formulation developed for preventing postoperative adhesions occurring between the manipulated tissues and organs. 
     BACKGROUND 
     After any kind of surgical intervention performed on living organisms, when the tissues that are cut in the operated site are healing, adhesions occur between the organs and tissues that are located at that site or neighboring that site due to fibrosis in the early period and collagen tissue accumulation in the late period. The resulting collagen tissue and the amount of adhesions depending thereon vary depending on many parameters such as the size and duration of the surgical intervention, whether the environment is infected, whether a foreign body (prosthetic material) is used, the amount of bleeding and the immune response power of the patient. However adhesions definitely occur after every surgical intervention. 
     Post-operative adhesions are a serious problem after any type of surgical intervention. The most common cause of intestinal obstruction, the most common cause of secondary laparotomy after abdominal operations, and the most common cause of female infertility are postoperative adhesions. Many studies are carried out to solve this serious problem. In the studies in the literature, liquid or soluble gelatinous materials with different contents and active substances that are absorbed over time are placed at the surgical site, but there is no definitive solution to the problem. 
     In applications performed in the prior art, liquid or soluble solid materials cause adhesions by inducing a natural foreign body reaction in the organism as they are not fully absorbed from the medium. These either directly damage the tissues they contact or the active substances they contain are insufficient to prevent adhesion formation. 
     SUMMARY 
     The objective of the present invention is to prevent postoperative adhesions, and in this context, to form a formulation comprising a mixture of glycerol, which is one of the most abundant biomolecules in the human body, and sodium pentaborate, which is known to have positive effects on wound healing. 
     This formulation is intended to act through blocking excessive fibrosis and collagen production occurring in the surgical site and accelerating wound healing. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       “A Glycerol and Sodium Pentaborate Based Formulation Preventing Postoperative Adhesions” developed to fulfill the objectives of the present invention is illustrated in the accompanying figures, in which: 
         FIG. 1  is a representation of the Glycerol formula, 
         FIG. 2  is a representation of the Sodium Pentaborate formula. 
         FIG. 3  is a representation of a case wherein the liquid of the present invention is not applied on the operated rat and there is an intense adhesion. 
         FIG. 4  is a representation of a case wherein the liquid of the present invention is applied on the operated rat and no adhesion is observed. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     The glycerol and sodium pentaborate based formulation of the present invention is used for preventing adhesions between the tissues and organs that are manipulated at the surgical site as a result of any kind of surgical intervention. This formulation described within the scope of the present invention is a mixture of glycerol, which is one of the most abundant biomolecules in the human body, and sodium pentaborate, which is known to have positive effects on wound healing. These two substances prevent postoperative adhesions thanks to both biocompatibility thereof and their positive effects on wound healing through blocking excessive fibrosis and collagen production. 
     Glycerol that is discussed within the scope of the invention is the main substance of the ester named triglyceride, which is the most abundant biomolecule in humans, animals and plants. Sodium pentaborate, which is another component, is a boron-based compound. Boron is a nonmetallic element with atomic number five and atomic weight of 10.8; and as it is located next to the carbon atom, which is the primary element of life, in the periodic table, it is very similar to this atom with its physical and chemical properties. Since boron is a very stable atom, it is not found free in nature and is generally found in a form called borate formed by its binding with O 2 . Borates are odorless white crystals and dissolve immediately in water. The simplest borates are boron oxide (B 2 O 3 ) and boric acid (H 2 BO 3 ). 
     The formulation of the present invention is a suspension of glycerol with a concentration of 1% to 10% and sodium pentaborate with a concentration of 1% to 10% in physiological saline solution or another inert and biocompatible liquid. The formulation particularly preferred within the scope of the invention is comprised of 1% glycerol and 3% sodium pentaborate. The suspension containing the formulation of the present invention is sprayed after any surgical intervention on the surfaces, where the surgery is performed, and where the hand of the surgeon or the surgical instruments used during the operation contact, and full contact thereof with these surfaces is ensured by applying light friction via hand for at least one minute. Then, using routine techniques, the wound is closed as the surgeon deems appropriate. The formulation prevents formation of post-operative adhesions by forming a layer on the surfaces of the tissues that it contacts for about 48-72 hours, and thereby, on one hand, preventing contact of these surfaces with the surrounding tissues, and on the other hand, accelerating wound healing on these surfaces and blocking excessive fibrosis and collagen tissue production. 
     In the experimental study conducted on rats, after the adhesion model application on the rat cecum tissue, the omentum tissue adhered to the cecum as seen in  FIG. 3 . However, it was observed that there was no adhesion to the cecum tissue in rats to which the formulation of the invention was applied ( FIG. 4 ).