Emulsions or microemulsions for use in endoscopic mucosal resectioning and/or endoscopic submucosal dissection

Abstract

The invention provides a pharmaceutical composition in form of emulsion or microemulsion for use in an endoscopic procedure, preferably said endoscopic procedure comprising the administration of said pharmaceutical composition to a human with the aim of improving and facilitating the resection of the lesion by raising the area where the lesion is located. The invention herein disclosed provides a method for performing an endoscopic procedure, said method preferably comprising the administration of a pharmaceutical composition in form of emulsion or microemulsion to a human. The invention herein disclosed also provides a kit for use in an endoscopic procedure, said kit comprising a pharmaceutical composition in form of emulsion or microemulsion, an endoscopic injection needle, a syringe and instructions for use thereof.

Description

[0001]The present invention relates to a pharmaceutical composition in form of emulsion or microemulsion and the use thereof as aid during endoscopic procedures in which it is injected in a target tissue in order to form a cushion. More in details, the invention relates to a method for performing an endoscopic procedure, which comprises injecting said pharmaceutical composition in form of emulsion or microemulsion in a target tissue of a patient, in order to form a cushion, which cushion is then optionally subjected to an endoscopic surgical procedure, such as a resection.BACKGROUND OF THE INVENTION[0002]Endoscopy is a diagnostic and medical procedure which allows to examine the interior of a hollow organ or cavity of the body by means of an instrument called endoscope, without employing invasive surgery. Endoscopy is commonly used for diagnostic purposes, even though minor, non-invasive surgical and non-surgical interventions can be performed during an endoscopic procedure. Typical...

AI Technical Summary

Benefits of technology

[0014]Said endoscopic procedure is preferably an endoscopic resection of the mucosa performed during a gastrointestinal endoscopy, more preferably a polypectomy, an endoscopic mucosal resection (EMR) and / or an endoscopic submucosal dissection (ESD).

[0015]According to the invention, said gastrointestinal endoscopy is preferably performed in the esophagous, stomach and / or small intestine (duodenum, jejunum, ileum), in the cecum, in the colon, in the sigmoid colon and / or in the rectum.

[0016]The invention herein disclosed provides a method for performing an endoscopic procedure, said method comprising the administration of a pharmaceutical composition in form of emulsion or microemulsion to a human, wherein said pharmaceutical composition in form of emulsion or microemulsion comprises at least one inverse thermosensitive polymer and at least one physiologically acceptable excipient. According to the invention, said endoscopic procedure is preferably an endoscopic resection of the mucosa performed during a gastrointestinal endoscopy, more preferably a polypectomy, an endoscopic mucosal resection (EMR) and / or an endoscopic submucosal dissection (ESD).

[0017]Said gastrointestinal endoscopy is preferably performed in the esophagous, stomach and / or small intestine (duodenum, jejunum, ileum), in the cecum, in the colon, in the sigmoid colon and / or in the rectum.

[0018]Further, the invention herein disclosed provides a kit for use in an endoscopic procedure, said kit comprising a pharmaceutical composition in form of emulsion or microemulsion, an endoscopic injection needle, a syringe and instruction for use thereof, wherein said pharmaceutical composition in form of emulsion or microemulsion comprises at least one inverse thermosensitive polymer and wherein said endoscopic procedure is preferably an endoscopic resection of the mucosa performed during a gastrointestinal endoscopy, more preferably a polypectomy, an endoscopic mucosal resection (EMR) and / or an endoscopic submucosal dissection (ESD).

Problems solved by technology

However, injection into the thin submucosal layer is a delicate process, the injected solution tends to dissipate quickly, flat and depressed lesions are hard to capture with the snare compared with protruded lesions, and large or awkwardly located lesions can be difficult to remove (Uraoka et al., Drug Design, Development and Therapy 2008:2 131-138).

Normal saline solution (NS) has been commonly used for this purpose, but it is difficult to produce the proper submucosal fluid cushion and maintain the desired height, particularly for flat elevated lesions, because of the rapid dispersion of the solution through the mucosal layers and absorption of NS into the surrounding tissue (Uraoka et al., Drug Design, Development and Therapy 2008:2 131-138).

For this reason, in long-lasting procedures and in the removal of large lesions, such as large flat polyps, repeated injection of the solution into the submucosal layer are required, with a consequent operational complication for the personnel of the endoscopic unit.

The main disadvantage of HA is its high cost, which renders it quite inaccessible for most endoscopic units.

Other solutions have been tested and described, such hypertonic dextrose and hydroxypropyl methylcellulose (HPMC), which however have been reported to cause tissue damage and inflammation.

The main disadvantage of FM is the possible the risk of transmission of viruses: since FM is obtained by the fractionalization of coagulation proteins in human serum, contamination with hepatitis or other viruses is possible.

However, the use of viscous solutions, such as HA solutions or HPMC solutions, poses some challenges in the procedure, due to the difficulty to get a viscous solution flowed through the injection devices.

For this reason, the viscous solutions used for EMRs and ESDs often need to be diluted before their use to make the solutions able to flow through the injection needle, with a loss of their characteristics of providing a high and long-lasting cushion.

However, the use of such a “high-pressure” generating device during the endoscopic examination is known for being not favorably accepted by the experts of the field, since it is cumbersome, additional work is required to put it in place, it is difficult to be operated and therefore it represents a complication of the EMR and ESD procedures.

HA (hyaluronic acid) provides viscous solutions capable of providing long-lasting submucosal cushions and is safe and non toxic, but it is known to be highly expensive.

Cellulose derivatives, such as HPMC and CMC, are cheap and their solutions are capable of providing long-lasting submucosal cushions; however, due to their viscosity, a particular device such a syringe pump is required to make them flow into the injection needle, thus they are known for being difficult and uncomfortable to be injected.

Accordingly, such polymers are usually contained in the known solutions in an amount equal to or above 15% by weight, with respect to the weight of the composition (namely, above the CGC); thus the viscosity of said solutions is too high to allow them to be manually injected, and the use of a syringe pump is needed, with an evident disadvantage for the endoscopist.

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