A combination and method for endoscopy

Abstract

This invention relates to a combination of actives that enables clear visibility for performing endoscopy Wherein the combination comprises a Defoamer agent, a Mucolytic agent, an Anti-peristaltic agent. The present invention further relates to a method of conducting endoscopy and related procedures on a subject wherein method comprises providing the subject with the combination of instant invention either before or during the endoscopy.

Description

A Combination and Method for Endoscopy

[0001] A Combination and Method for EndoscopyRELATED APPLICATION

[0002] This application claims the benefit of application IN 202511004364, filed on 20thJanuary, 2025, the disclosure of which is hereby incorporated herein by reference in its entirety.

[0003] This invention relates to a combination of actives. The said combination enables clear visibility for performing endoscopy Wherein the combination comprises a Defoamer agent, a Mucolytic agent, an Anti-peristaltic agent. The combination may optionally comprise one more agent selected from Anesthetic agent, dye, stabilizers, other auxiliary agents and combinations thereof. The present invention further relates to a method of conducting endoscopy and related procedures on a subject wherein method comprises providing the subject with the combination of instant invention either before or during the endoscopy.BACKGROUND OF THE INVENTION

[0004] Endoscopy is a medical procedure that allows doctors to view the hollow lumens of a subject using an endoscope, a flexible tube with a light and camera attached to it. This technique is commonly used to examine the gastrointestinal (GI) tract, including the oesophagus, stomach, and intestines, as well as other parts of the body such as the respiratory tract, ear, female reproductive system and urinary system.

[0005] However, despite the technical improvements in the equipment for better imaging several challenges persist to navigate and detect the abnormalities. For example, folds in the gastrointestinal tract, presence of bubbles, mucous and peristaltic movements hinders the diagnostic and therapeutic ability of the performing endoscopist.

[0006] To overcome these challenges, pre-endoscopic drinks are at times provided to patients. Alternatively, flushes using different actives have also been used during endoscopy to clear the impediments. Lack of proper cleansing of GI tract may lead to poor quality outcome of endoscopy. The movements of intestines also hinder between the process thus reducing the quality of the outcome.

[0007] Apart from visibility issues, endoscopic procedures also pose comfort issues to the patient, especially an uncomfortable gag reflex during inserting the upper gastrointestinal endoscope(s). Thus leading to poor compliance and a messy endoscopic procedure. This also cause issue of compliance on subject’s part. Continuous efforts are being made to provide solutions that provide an easy experience for subject(s) while ensuring better results from endoscopy. Subject(s) may also suffer from gag response, thus making it difficult to perform the procedure. Several relaxation techniques are advised to make a subject comfortable and prevent gag response. The problems increases if the subject is a senior citizen, children, a mental patient, pet / animal or someone with complicated medical condition including issues of anxiety.

[0008] The existing literature with proposed pre endoscopy preparation(s) have their own challenges including, unpleasant taste or smell, high volumes of liquid needed which might increase the risk of aspiration and most importantly; nearly all of them are available as individual actives and need separate ingestion greatly hindering the compliance to such preparations. Further, some subjects may have sensitivity to anesthetic agent.

[0009] Thus, there lies a need to devise a solution that enables a easier, quicker, better and cost-effective solution to above mentioned and related problems. It goes without saying that if the visibility is clear, the better identification of even subtle abnormality and its subsequent treatment is possible.

[0010] CN102470183 discloses a composition comprising dimethicone / simethicone and acetylcysteine or pharmaceutically acceptable salts thereof. The CN102470183 discloses the combination of simethicone and acetylcysteine only.

[0011] Peter et al, Endosc Int Open 2016; 04(11): E1197-E1202 discloses a pre-procedure drink containing simethicone and NAC that improves mucosal visibility during gastroscopy and reduces the need for flushes during the procedure. However, Peter et al fails to reduce the peristalsis movement of the GI tract, further it is also moot about any specific method to and use as illustrated in the instant invention.

[0012] Shrihari et al, J Digest Endosc 2021;12:11–18 also discloses a pre-endoscopy drink of NAC with simethicone however fails to reduce the peristalsis movement of the GI tract, further it is also moot about any specific method to and use as illustrated in the instant invention.

[0013] The present invention aims to provide solution to above mentioned problems by providing a combination that can be administered to a subject either before endoscopy or during endoscopy, wherein the said combination cleans the gastrointestinal tract and provides a clear view.

[0014] The present invention also provides a method of conducting an endoscopy which includes providing the subject with the combination of instant invention.

[0015] The present invention also provides a method to ease the subjects’ discomfort with the help of instant invention.OBJECT OF THE INVENTION

[0016] It is an object of the invention to provide a combination comprising a defoamer, mucolytic agent and anti-peristaltic agent.

[0017] It is another object of the invention to provide a composition or pre-mix comprising a combination of a defoamer, mucolytic agent and anti-peristaltic agent.

[0018] It is another object of the invention to provide a formulation comprising a combination of a defoamer, mucolytic agent and anti-peristaltic agent.

[0019] It is another object of the invention to provide a method of performing an endoscopy on a subject.

[0020] It is yet another object of the invention to provide use the combination of present disclosure for performing endoscopy.

[0021] It is another object of the invention to provide a combination for cleaning path of the tract where endoscopy is to be performed.

[0022] It is another object of the invention to provide a method for cleaning path of the tract where endoscopy is to be performed.

[0023] It is another object of the invention to improve the compliance of subject for conducting endoscopy.

[0024] It is another object of the invention to provide a kit to prepare the combination comprising a defoamer, mucolytic agent and anti-peristaltic agent.

[0025] It is yet another object of the invention to provide a kit comprising the instructions to prepare the combination comprising a defoamer, mucolytic agent and anti-peristaltic agent.

[0026] It is yet another object of the invention to provide a method to ease the discomfort of the patient for endoscopy.SUMMARY OF THE INVENTION

[0027] It is an aspect of the invention to provide a combination comprising a defoamer, mucolytic agent and anti-peristaltic agent.

[0028] It is another aspect of the invention to provide a combination comprising defoamer, mucolytic agent and anti-peristaltic agent and optionally one or more agent selected from Anesthetic agent, dye, stabilizers, other auxiliary agents and combinations thereof.

[0029] It is another aspect of the invention to provide a composition or pre-mix comprising a combination of a defoamer, mucolytic agent and anti-peristaltic agent.

[0030] It is another aspect of the invention to provide a composition or pre-mix comprising a combination of a defoamer, mucolytic agent, anti-peristaltic agent and optionally one or more agent selected from Anesthetic agent, dye, stabilizers, other auxiliary agents and combinations thereof.

[0031] It is another aspect of the invention to provide a formulation comprising a combination of a defoamer, mucolytic agent and anti-peristaltic agent.

[0032] It is another aspect of the invention to provide a method of performing an endoscopy on a subject with the combination of actives.

[0033] It is yet another aspect of the invention to provide use of the combination for performing endoscopy.

[0034] It is another aspect of the invention to provide the combination for cleaning path of the tract where endoscopy is to be performed.

[0035] It is another aspect of the invention to provide a method for cleaning path of the tract where endoscopy is to be performed.

[0036] It is another aspect of the invention to improve the compliance of subject for conducting endoscopy.

[0037] It is yet another aspect of the invention to provide a kit comprising the active and instructions to prepare the combination.

[0038] It is yet another aspect of the invention to provide a method to ease the discomfort of the patient for endoscopy.DETAILED DESCRIPTION OF THE INVENTION

[0039] It is an embodiment of the invention to provide a combination comprising a defoamer, mucolytic agent and anti-peristaltic agent.

[0040] In another embodiment the invention provides a combination comprising defoamer, mucolytic agent and anti-peristaltic agent and optionally one or more agent selected from Anesthetic agent, dye, stabilizers, other auxiliary agents and combinations thereof.

[0041] In another embodiment the invention provides a composition or pre-mix comprising a combination of actives selected from a defoamer, mucolytic agent and anti-peristaltic agent.

[0042] In another embodiment the invention provides a composition or pre-mix comprising a combination of actives selected from defoamer, mucolytic agent, anti-peristaltic agent and optionally one or more agent selected from Anesthetic agent, dye, stabilizers, other auxiliary agents and combinations thereof.

[0043] In another embodiment the invention provides a formulation comprising a combination comprising defoamer, mucolytic agent and anti-peristaltic agent.

[0044] In another embodiment the invention provides a method of performing an endoscopy on a subject with the combination as per the instant disclosure.

[0045] In another embodiment the invention provides use of combination of instant disclosure for performing an endoscopy.

[0046] In another embodiment the invention provides the combination has capability for cleaning path of the tract where endoscopy is to be performed.

[0047] In another embodiment the invention provides a method for cleaning path of the tract where endoscopy is to be performed.

[0048] In another embodiment the invention provides a method to improve the compliance of subject for conducting endoscopy.

[0049] In yet another embodiment the invention provides a kit comprising the active and instructions to prepare the combination.

[0050] In another embodiment the combination comprises a defoamer, a mucolytic agent and an anti-peristaltic agent.

[0051] In yet another embodiment a defoamer is selected from simethicone, GI-Ease (a ginger based supplement), peppermint oil, or any other water or oil soluble defoamer.

[0052] In yet another embodiment mucolytic agent is selected from N-acetylcysteine, Dithiothreitol, Erdosteine, P3001, , pronase or any other mucolytic agent.

[0053] In yet another embodiment anti-peristaltic agent is selected from L-menthol, Levomenthol, loperamide, hyoscine-N-butylbromide (HBB), mint oil or any other anti-peristaltic agent.

[0054] In yet another embodiment the anesthetic agent is selected from lidocaine, Marcaine, Nesacaine, Altacaine, Benzodent, Articaine, Xylocaine, Diphenhydramine or any other anesthetic agent.

[0055] In yet another embodiment dye is selected from methylene blue, Congo red, indigo carmine and toluidine blue, indocyanine green, cresyl violet or any other dye for better detection of abnormality.

[0056] In yet another embodiment the auxiliary agent is selected from surfactant, pH regulating agent, buffer, stabilizing agent, binders, fillers, disintegrants, lubricants, preservatives, colorants, flvaoring agents, solvents, coating agents.

[0057] In yet another embodiment surfactant is selected from but not limited to polyoxyethylensorbitan fatty acid esters (Tween), polyoxyethylene alkyl ethers (Brij), alkylphenylpolyoxyethylene ethers (Triton-X), polyoxyethylene-polyoxypropylene copolymer (Poloxamer, Pluronic), and sodium dodecyl sulfate (SDS). Examples of suitable polyoxyethylenesorbitan-fatty acid esters are polysorbate 20, and polysorbate 80 or combinations thereof.

[0058] In yet another embodiment pH regulating agents are selected from but not limited to citric acid, sodium hydroxide, hydrochloric acid, sodium bicarbonate, phosphoric acid, potassium hydroxide, acetic acid and ammonium hydroxide or combinations thereof.

[0059] In yet another embodiment buffer is selected from but not limited to acetate buffer, phosphate buffer, citrate buffer, tris buffer, MES buffer, MOPS buffer or combination thereof.

[0060] In yet another embodiment stabilizing agent is selected from but not limited to ascorbic acid, Butylated Hydroxytoluene, Sodium Metabisulfite, EDTA (Ethylenediaminetetraacetic Acid), Propyl Gallate or combinations thereof.

[0061] In yet another embodiment preservatives are selected from but not limited to Benzalkonium Chloride, Methylparaben, Propylparaben, phenol, Chlorobutanol, Thimerosal, Sodium Benzoate, Benzyl Alcohol or combinations thereof.

[0062] In yet another embodiment, flavouring agent is selected from but not limited to sucrose, sorbitol, mannitol, vanillin, menthol, cherry flavour, orange flavour, strawberry flavour, lemon flavour, watermelon flavour, apple flavour, mango flavour, guava flavour or combinations thereof.

[0063] In yet another embodiment, solvent is selected from inorganic solvent, organic solvent or water.

[0064] In yet another embodiment the composition is a formulation.

[0065] In yet another embodiment, formulation is solid formulation or liquid formulation.

[0066] In yet another embodiment, solid formulation is selected form tablet, capsules, powders, granules, pills and pellets.

[0067] In yet another embodiment liquid formulation is selected from suspensions, solutions, emulsions, tinctures and drops.

[0068] In yet another embodiment the composition is ready to use composition.

[0069] In yet another embodiment the composition requires dilution with water before use.

[0070] In yet another embodiment the composition can be administered directly to the subject.

[0071] In another embodiment present invention provides a method of conducting endoscopy on a subject.

[0072] In yet another embodiment the method comprises:Preparing the combination as per the present disclosure;administering the combination to a subject, atleast 5-30 minutes before conducting endoscopy;conducting the endoscopy.

[0073] In yet another embodiment the method comprises:Administering the combination or composition as per present disclosure to the subject atleast 5-30 minutes before conducting endoscopy;conducting the endoscopy.

[0074] In yet another embodiment, the method of conducting endoscopy comprises:Administering the combination or composition as per present disclosure to the subject atleast 5-30 minutes before conducting endoscopy;optionally applying anesthetic agent on the endoscope or locally on the subject to prevent the gag response;conducting the endoscopy.

[0075] In yet another embodiment, the method of conducting endoscopy comprises:Administering the combination or composition as per present disclosure as flush to the subject during the time of endoscopy;conducting the endoscopy.

[0076] In yet another embodiment the invention provides a method of cleaning tract of the subject before endoscopy wherein the said method comprises administering the combination as per the instant disclosure.

[0077] In yet another embodiment the invention provides use of combination comprising defoamer, mucolytic agent and anti-peristaltic agent as a pre-mix for clearing the tract of the subject.

[0078] It is yet another embodiment of the invention that the combination or composition or pre-mix of the present disclosure can be provided as a pre-drink or as flush.

[0079] It is yet another embodiment that the combination or composition or pre-mix as disclosed in the instant disclosure can be administered orally or intravenously.

[0080] In yet another embodiment the invention provides a method of making subject comfortable for conducting endoscopy.

[0081] In yet another embodiment the subject is human or animal.

[0082] In yet another embodiment the subject is a human.

[0083] In another embodiment the subject is an animal.

[0084] In another embodiment the subject is a pet animal.

[0085] In yet another embodiment endoscopy technique is selected from colonoscopy, upper endoscopy, bronchoscopy, enteroscopy, capsule endoscopy, Endoscopic retrograde cholangiopancreatography (ERCP), anoscopy, proctoscopy, rectoscopy and / or a sigmoidoscopy

[0086] In yet another embodiment combination of instant disclosure additionally comprises a dye.

[0087] In yet another embodiment the combination comprises:

[0088] defoamer selected from simethicone, GI-Ease (a ginger based supplement), peppermint oil, or any other water or oil soluble defoamer;

[0089] mucolytic agent selected from N-acetylcysteine, Dithiothreitol, Erdosteine, P3001, Steam inhaler, Dry powder mannitol (Bronchitol), pronase or any other mucolytic agent; and

[0090] anti-peristaltic agent selected from L-menthol, Levomenthol, loperamide, hyoscine-N-butylbromide (HBB), mint oil or any other anti-peristaltic agent.

[0091] In yet another embodiment the combination comprises: defoamer selected from simethicone, GI-Ease (a ginger based supplement), peppermint oil, or any other water or oil soluble defoamer; mucolytic agent selected from N-acetylcysteine, Dithiothreitol, Erdosteine, P3001, Steam inhaler, Dry powder mannitol (Bronchitol), pronase or any other mucolytic agent; anti-peristaltic agent selected from L-menthol, Levomenthol, loperamide, hyoscine-N-butylbromide (HBB), mint oil or any other anti-peristaltic agent; and optionally an anesthetic agent is selected from lidocaine, Marcaine, Nesacaine, Altacaine, Benzodent, Articaine, Xylocaine, Diphenhydramine or any other anesthetic agent.

[0092] In yet another embodiment the combination comprises: defoamer selected from simethicone, GI-Ease (a ginger based supplement), peppermint oil, or any other water or oil soluble defoamer; mucolytic agent selected from N-acetylcysteine, Dithiothreitol, Erdosteine, P3001, Steam inhaler, Dry powder mannitol (Bronchitol), pronase or any other mucolytic agent; anti-peristaltic agent selected from L-menthol, Levomenthol, loperamide, hyoscine-N-butylbromide (HBB), mint oil or any other anti-peristaltic agent; and optionally a dye or an anesthetic agent or combinations thereof.

[0093] In yet another embodiment the combination comprises:Simethicone;N-acetylcysteine;L-menthol

[0094] In yet another embodiment the combination comprises:simethicone;N-acetylcysteine;L-mentholLidocaine

[0095] In yet another embodiment the combination comprises:simethicone;N-acetylcysteine;L-mentholLidocaineDye

[0096] In yet another embodiment the combination comprises:simethicone;N-acetylcysteine;L-mentholDye

[0097] In yet another embodiment the combination comprises:defoamer selected from simethicone, GI-Ease (a ginger based supplement), peppermint oil, or any other water or oil soluble defoamer;mucolytic agent selected from N-acetylcysteine, Dithiothreitol, Erdosteine, P3001, Steam inhaler, Dry powder mannitol (Bronchitol), pronase or any other mucolytic agent;anti-peristaltic agent selected from L-menthol, Levomenthol, loperamide, hyoscine-N-butylbromide (HBB), mint oil or any other anti-peristaltic agent; andoptionally an anesthetic agent is selected from lidocaine, Marcaine, Nesacaine, Altacaine, Benzodent, Articaine, Xylocaine, Diphenhydramine or any other anesthetic agent.Optionally an auxiliary agent.

[0098] In yet another embodiment the combination consisting of:defoamer selected from simethicone, GI-Ease (a ginger based supplement), peppermint oil, or any other water or oil soluble defoamer;mucolytic agent selected from N-acetylcysteine, Dithiothreitol, Erdosteine, P3001, Steam inhaler, Dry powder mannitol (Bronchitol), pronase or any other mucolytic agent;anti-peristaltic agent selected from L-menthol, Levomenthol, loperamide, hyoscine-N-butylbromide (HBB), mint oil or any other anti-peristaltic agent; andoptionally an anesthetic agent is selected from lidocaine, Marcaine, Nesacaine, Altacaine, Benzodent, Articaine, Xylocaine, Diphenhydramine or any other anesthetic agent.atleast one auxiliary agent.

[0099] In yet another embodiment the composition comprises:Combination as per the instant disclosure; andauxiliary agent selected from surfactant, pH regulating agent, buffer, stabilizing agent, binders, fillers, disintegrants, lubricants, preservatives, colorants, flavouring agents, solvents, coating agents

[0100] In yet another embodiment the composition comprises:Defoamer;Mucolytic agent;Anti-peristaltic agent; andauxiliary agent selected from surfactant, pH regulating agent, buffer, stabilizing agent, binders, fillers, disintegrants, lubricants, preservatives, colorants, flavouring agents, solvents, coating agents.

[0101] In yet another embodiment the composition comprises:simethicone;N-acetylcysteine;L-menthol andauxiliary agent is selected from surfactant, pH regulating agent, buffer, stabilizing agent, binders, fillers, disintegrants, lubricants, preservatives, colorants, flavoring agents, solvents, coating agents.

[0102] In yet another embodiment, a kit comprises:Defoamer;Mucolytic agent;Anti-peristaltic agent; andManual instructions to combine the actives and administer to the subject.

[0103] In yet another embodiment, a kit comprises:a combination of defoamer and Mucolytic agent;Anti-peristaltic agent; andManual instructions to combine the actives and administer to the subject

[0104] In yet another embodiment, combination with dye provide better contrast.

[0105] In yet another embodiment, the combination of dye with combination of defoamer, mucolytic agent and anti-peristaltic agent could also mean localised spraying / flushing of dye while performing endoscopy; wherein the subject has been provided or will be provided with the combination of defoamer, mucolytic agent and anti-peristaltic agent.

[0106] In yet another embodiment, the combination of anesthetic agent with combination of defoamer, mucolytic agent and anti-peristaltic agent could also mean localised spraying / flushing of anesthetic while performing endoscopy; wherein the subject has been provided or will be provided with the combination of defoamer, mucolytic agent and anti-peristaltic agent.

[0107] In yet another embodiment anesthetic agent provide comfort and prevent gag response in the subject.

[0108] In yet another embodiment, the combination additionally comprising flavouring agent improves the taste and palatability of the combination.

[0109] In yet another embodiment the defoamer is in the range of 1-1000 mg, preferably in the range of 1-500mg, 10-500 mg, more preferably 20-300 mg, more preferably 20-200 mg in 100 ml of solution.

[0110] In yet another embodiment the mucolytic agent is in the range of 10-1500 mg, 50-1000mg, preferably 100-800 mg, 150-700mg, and more preferably 200-700 mg, 200-650mg per 100 ml of solution.

[0111] In yet another embodiment the anti-peristaltic agent is present in the range of 0.01%-0.5%, preferably in the range of 0.05%-0.5%, more preferably in the range of 0.1%-0.3% per 100 ml of solution.

[0112] In yet another embodiment the anti-peristaltic agent is present in the range of 80mg- 300 mg, preferably in the range of 100mg-250mg, more preferably 150mg-200mg per 100 ml of solution.

[0113] Examples:

[0114] The following examples are provided for the purpose of illustrating the present invention but without limiting the scope thereof.

[0115] Example 1:

[0116] Pre-endoscopic Drink:S. No.Ingredient(s)11 ml of 40 mg Simethicone emulsion2One tablet comprising 600 mg N-acetylcysteine320 ml of 0.8 % w / v Levomenthol solution4Water – 100 ml

[0117] The pre-drink of the instant disclosure has shown positive patient satisfaction, better mucosal visibility and reduced peristalsis whether provided as pre-drink before endoscopy or as flush.

[0118] Example 2:

[0119] The patient was provided with the pre-drink of example 1 and lidocaine was applied locally.

[0120] The lack of gag response enhanced the patient comfort at the same time improved mucosal visibility as there was no sudden fogging from refluxed secretions, and no abrupt camera displacement. This also reduced the need for repeated flushing which is required in patients with active gag response.

Claims

A combination comprising:a defoamer agent;a mucolytic agent;an anti-peristaltic agent; andOptionally an auxiliary agent;wherein the defoamer is in the range of 1-1000 mg, in 100 ml of solution;the mucolytic agent is in the range of 10-1500 mg, per 100 ml of solution and;the anti-peristaltic agent is in the range of 0.01%-0.5%, per 100 ml of solution.The defoamer as claimed in claim 1, is selected from simethicone, GI-Ease (a ginger based supplement), peppermint oil.The mucolytic agent as claimed in claim 1 is selected from N-acetylcysteine, Dithiothreitol, Erdosteine, P3001, pronase.The anti-peristaltic agent as claimed in claim 1 is selected from L-menthol, Levomenthol, loperamide, hyoscine-N-butylbromide (HBB), mint oil.The combination as claimed in claim 1 optionally comprises an anesthetic agent selected from lidocaine, Marcaine, Nesacaine, Altacaine, Benzodent, Articaine, Xylocaine and Diphenhydramine.The combination as claimed in claim 1, optionally comprising a dye for enhanced lesion contrast.The combination as claimed in claim 1, is a ready-to-use pre-mix.A method of cleaning the tract for conducting endoscopy, wherein the method comprising:Administering the combination or composition as per present disclosure to the subject atleast 5-30 minutes before conducting endoscopy;conducting the endoscopy.The method as claimed in claim 8, optionally comprises applying anesthetic agent on the endoscope or locally on the subject to prevent the gag response before the step b.A kit comprising:a defoamer agent;a mucolytic agent;an anti-peristaltic agent; andwritten instructions directing administration of the agents prior to or during endoscopy to improve mucosal visibility.