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.

1 . A pharmaceutical composition in form of emulsion or microemulsion comprising:
 a) an aqueous phase;   b) an oily phase;   c) at least one surfactant;   d) at least one inverse thermosensitive polymer;   e) optionally at least one physiologically acceptable excipient;   wherein said pharmaceutical composition is for use as aid during endoscopic procedures in which it is injected in a target tissue in order to form a cushion.   
     
     
         2 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , wherein said composition is an oil-in-water emulsion. 
     
     
         3 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , wherein said at least one inverse thermosensitive polymer is contained in an amount between about 2% and about 30% with respect to the weight of the composition, preferably between about 5% and about 25% by weight, more preferably between about 8% and about 20% by weight, with respect to the weight of the composition. 
     
     
         4 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , wherein said at least one inverse thermosensitive polymer is a polyoxyethylene-polyoxypropylene block copolymer, preferably a poloxamer. 
     
     
         5 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 4 , wherein said poloxamer is selected from poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, and poloxamer 407, preferably poloxamer 188, poloxamer 407 or a mixture of poloxamer 188 and poloxamer 407. 
     
     
         6 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , wherein said oily phase comprises at least one lipophilic compound. 
     
     
         7 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 6 , wherein said at least one lipophilic compound is selected from natural oils, such as almond oil, canola oil, castor oil, corn oil, cottonseed oil, olive oil, safflower oil, sesame oil, soybean oil and the like; fatty acid esters, such as isopropyl palmitate, isopropyl myristate, ethyl oleate and the like; fatty alcohols, such as myristic alcohol, oleyl alcohol and the like; fatty acids, such as myristic acid, oleyl acid, palmitic acid and the like. 
     
     
         8 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 7 , wherein said at least one lipophilic compound is selected from soybean oil and medium-chain triglycerides. 
     
     
         9 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , wherein said at least one surfactant is a non-ionic surfactant, a ionic surfactant or a mixture thereof. 
     
     
         10 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 9 , wherein said non-ionic surfactant is selected from polysorbate 80 and PEG-15 hydeoxystearate. 
     
     
         11 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 9 , wherein said ionic surfactant is selected from egg lecithin, hydrogenated phosphatidyl choline from egg lecithin, soybean lecithin and hydrogenated soybean lecithin. 
     
     
         12 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , further comprising at least one co-surfactant. 
     
     
         13 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 12 , wherein said co-surfactant is selected from propylene glycol, glycerol and sodium oleate. 
     
     
         14 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 12 , wherein said co-surfactant is a mixture of glycerol and sodium oleate. 
     
     
         15 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , further comprising at least one dye. 
     
     
         16 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 15 , wherein said at least one dye is a vital dye, non-vital dye, reactive dye or a mixture thereof. 
     
     
         17 . The pharmaceutical composition in form of emulsion or microemulsion for use in an endoscopic procedure according to  claim 15 , wherein said dye is selected from Lugol's solution, methylene blue, toluidine blue, crystal violet, indigo carmine, congo red and phenol red. 
     
     
         18 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 17 , wherein said dye is methylene blue or indigo carmine. 
     
     
         19 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , wherein said endoscopic procedure is an endoscopic resection procedure performed during a gastrointestinal endoscopy, preferably a polypectomy, an endoscopic mucosal resection (EMR) and/or an endoscopic submucosal dissection (ESD). 
     
     
         20 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , wherein said endoscopic procedure is performed in the esophagous, stomach, small intestine, cecum, colon, sigmoid colon and/or rectum. 
     
     
         21 . The pharmaceutical composition in form of emulsion or microemulsion for use according to  claim 1 , wherein said endoscopic procedure comprises the administration of said composition to a human. 
     
     
         22 . A kit for use in an endoscopic procedure, said kit comprising:
 a) a pharmaceutical composition in form of emulsion or microemulsion according to  claim 1 ;   b) an endoscopic injection needle;   c) instruction for use.   
     
     
         23 . The kit for use in an endoscopic procedure according to  claim 21 , wherein said pharmaceutical composition in form of emulsion or microemulsion is packaged in ampoules, vials, bottles, pre-filled syringes. 
     
     
         24 . The kit for use in an endoscopic procedure according to  claim 22 , wherein said pharmaceutical composition in form of emulsion or microemulsion is packaged in 5 mL or 10 mL pre-filled syringes. 
     
     
         25 . The kit for use in an endoscopic procedure according to  claim 22 , wherein said pharmaceutical composition in form of emulsion or microemulsion is packaged in 10 mL, 20 mL or 50 mL vials or in 10 mL, 20 mL or 50 mL ampoules. 
     
     
         26 . The kit for use in an endoscopic procedure according to  claim 22 , wherein said endoscopic injection needle has a diameter of the needle ranging from 12 gauge to 35 gauge, preferably from 15 gauge to 30 gauge, more preferably from 17 gauge to 28 gauge. 
     
     
         27 . The kit for use in an endoscopic procedure according to  claim 22  wherein said endoscopic injection needle has a length ranging from 100 cm to 300 cm, preferably from 120 cm to 260 cm, more preferably from 140 cm to 250 cm. 
     
     
         28 . The kit for use in an endoscopic procedure according to  claim 22 , wherein said endoscopic injection needle has an outer diameter ranging from 1.0 mm to 4.0 mm, preferably from 1.5 mm to 3.0 mm, more preferably from 1.8 mm to 2.5 mm. 
     
     
         29 . The kit for use in an endoscopic procedure according to  claim 22 , wherein said endoscopic injection needle is composed of materials selected in the groups comprising, but not limited to: polymers or copolymers, such as polyethylene (PE), polypropylene (PP), polyvinylchloride (PVC), polycarbonate (PC), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), polystyrene (PS), polyamide (PA), epoxy resins, polyurethane, polyester, polymethyl methacrylate and the like; rubbers, such as silicone rubber, natural rubber and the like; metals and metal alloys such as aluminum, titanium, iron, chromium, nickel, molybdenum, stainless steel, and the like. 
     
     
         30 . The kit for use in an endoscopic procedure according to  claim 22 , comprising a) a plastic catheter with a luer lock connection to the body of an injection syringe and b) a retractable needle. 
     
     
         31 . A pharmaceutical composition in form of emulsion or microemulsion comprising:
 a) an aqueous phase;   b) an oily phase;   c) at least one surfactant;   d) at least one inverse thermosensitive polymer;   e) optionally at least one dye optionally at least one physiologically acceptable excipient.   
     
     
         32 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 31 , wherein said composition is an oil-in-water emulsion or microemulsion. 
     
     
         33 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 31 , wherein said at least one inverse thermosensitive polymer is contained in an amount between about 2% and about 30% with respect to the weight of the composition, preferably between about 5% and about 25% by weight, more preferably between about 8% and about 20% by weight, with respect to the weight of the composition. 
     
     
         34 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 31 , wherein said at least one inverse thermosensitive polymer is a polyoxyethylene-polyoxypropylene block copolymer, preferably a poloxamer. 
     
     
         35 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 34 , wherein said poloxamer is selected from poloxamer 124, poloxamer 188, poloxamer 237, poloxamer 338, and poloxamer 407, preferably poloxamer 188, poloxamer 407 or a mixture of poloxamer 188 and poloxamer 407. 
     
     
         36 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 31 , wherein said oily phase comprises at least one lipophilic compound. 
     
     
         37 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 36 , wherein said at least one lipophilic compounds is selected from natural oils, such as almond oil, canola oil, castor oil, corn oil, cottonseed oil, olive oil, safflower oil, sesame oil, soybean oil and the like; fatty acid esters, such as isopropyl palmitate, isopropyl myristate, ethyl oleate and the like; fatty alcohols, such as myristic alcohol, oleyl alcohol and the like; fatty acids, such as myristic acid, oleyl acid, palmitic acid and the like. 
     
     
         38 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 37 , wherein said at least one lipophilic compound is selected from soybean oil and medium-chain triglycerides. 
     
     
         39 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 31 , wherein said at least one surfactant is a non-ionic surfactant, a ionic surfactant or a mixture thereof. 
     
     
         40 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 39 , wherein said non-ionic surfactant is selected from polysorbate 80 and PEG-15 hydeoxystearate. 
     
     
         41 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 40 , wherein said ionic surfactant is selected from egg lecithin, hydrogenated phosphatidyl choline from egg lecithin, soybean lecithin and hydrogenated soybean lecithin. 
     
     
         42 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 31 , further comprising at least one co-surfactant. 
     
     
         43 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 42 , wherein said co-surfactant is selected from propylene glycol, glycerol and sodium oleate. 
     
     
         44 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 43 , wherein said co-surfactant is a mixture of glycerol and sodium oleate. 
     
     
         45 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 31 , wherein said at least one dye is selected from Lugol's solution, methylene blue, toluidine blue, crystal violet, indigo carmine, congo red and phenol red. 
     
     
         46 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 45 , wherein said at least one dye is methylene blue or indigo carmine. 
     
     
         47 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 1 , wherein said emulsion or microemulsion has an improved flowability. 
     
     
         48 . The pharmaceutical composition in form of emulsion or microemulsion according to  claim 1 , wherein said emulsion or microemulsion is able to free flow in a catheter for injection to a target tissue.