Solid composition for the oral administration of dyes and diagnostic use thereof

Patent metadata

Field	Value
Publication number	US-9402922-B2
Application number	US-201313932321-A
Country	US
Kind code	B2
Filing date	Jul 1, 2013
Priority date	Mar 4, 2010
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

Abstract

The present application discloses solid compositions for the oral administration of dyes, and diagnostic use thereof. Preferably, such diagnostic use is aimed at the diagnostic evaluation of the gastrointestinal tract.

First claim

The invention claimed is:

1. A method of endoscopic diagnostic evaluation of pathologies of the small intestine and/or the large intestine in a subject, said method comprises administering to the subject a diagnostically effective amount of at least one solid composition within a 24 hour period preceding the endoscopic diagnostic evaluation and endoscopic diagnostically evaluating the small intestine and/or the large intestine for said pathologies, said solid composition comprising:
(a) at least one dye selected from among methylene blue, congo red, carmine indigo, toluidine blue or mixtures thereof;
(b) a first matrix in which said at least one dye is incorporated, wherein said first matrix comprises at least one lipophilic compound having a melting point below 90° C. and at least one amphiphilic compound, wherein said at least one amphiphilic compound is selected from among polar lipids of type I or II, ceramides, glycol alkyl ethers, or alkyl sulfosuccinate salts and wherein said polar lipids of type I or II are selected from among lecithin, phosphatidylcholine, phosphatidylethanolamine or mixtures thereof, and said glycol alkyl ether is diethylene glycol monomethyl ether;
(c) a second matrix comprising at least one hydrophilic compound, wherein the first matrix is dispersed in the second matrix;
(d) optionally other physiologically acceptable excipients; and
(e) optionally a gastro-resistant coating.

2. The method of claim 1 , wherein the solid composition is in form of a tablet or a capsule.

3. The method of claim 1 , wherein said at least one lipophilic compound is selected from among saturated, unsaturated or hydrogenated long chain alcohols, saturated, unsaturated or hydrogenated fatty acids, salts thereof, esters or amides, mono-, di- or triglycerides of fatty acids, waxes, ceramides, or cholesterol.

4. The method of claim 1 , wherein said at least one hydrophilic compound is a compound forming hydrogel.

5. The method of claim 1 , wherein said solid composition comprises a gastro-resistant coating and wherein the gastro-resistant coating is selected from among polymers of acrylic or methacrylic acid, copolymers of acrylic or methacrylic acid, cellulose acetate phthalate, hydroxybutyrate-based polymers, shellac or mixtures thereof.

6. The method of claim 1 , wherein said administration is carried out once or repeatedly.

7. The method of claim 1 , wherein the pathologies are inflammatory, ulcerative, dysplastic,pre-neoplastic or neoplastic pathologies.

8. The method of claim 1 , wherein the pathologies are cancerous or precancerous forms, polyps, pseudopolyps or different inflammatory pathologies of the small intestine and/or the large intestine.

9. The method of claim 1 , wherein said at least one dye is comprised in an amount ranging between 10 mg and 1500 mg or in an amount ranging between 50 mg and 1200 mg.

10. The method of claim 1 , wherein said at least one dye is comprised in an amount ranging between 2 mg and 1000 mg or in an amount ranging between 10 mg and 500 mg.

11. The method of claim 1 , wherein said at least one dye is comprised in an amount ranging between 20 mg and 500 mg or in an amount ranging between 25 mg and 400 mg.

12. The method of claim 1 , wherein said at least one dye is comprised in an amount equivalent to about 25 mg or in an amount equivalent to about 50 mg or in an amount equivalent to about 200 mg.

13. A method of endoscopic diagnostic evaluation of pathologies of the small intestine and/or the large intestine in a subject, said method comprises administering to the subject a diagnostically effective amount of at least one solid composition and endoscopic diagnostically evaluating the small intestine and/or the large intestine for said pathologies, wherein said solid composition is for oral administration and comprises:
(a) at least one dye selected from among methylene blue, congo red, carmine indigo, toluidine blue or mixtures thereof;
(b) a first matrix in which said at least one dye is incorporated, wherein said first matrix comprises at least one lipophilic compound having a melting point below 90° C. and at least one amphiphilic compound; wherein said at least one amphiphilic compound is selected from among polar lipids of type I or II, ceramides, glycol alkyl ethers, or alkyl sulfosuccinate salts and wherein said polar lipids of type I or II are selected from among lecithin, phosphatidylcholine, phosphatidylethanolamine or mixtures thereof, and said glycol alkyl ether is diethylene glycol monomethyl ether;
(c) a second matrix comprising at least one hydrophilic compound, wherein the first matrix is dispersed in the second matrix;
(d) optionally other physiologically acceptable excipients; and
(e) optionally a gastro-resistant coating.

14. The method of claim 13 , wherein the solid composition is in form of a tablet or capsule.

15. The method of claim 13 , wherein said at least one lipophilic compound is selected from among saturated, unsaturated or hydrogenated long chain alcohols, saturated, unsaturated or hydrogenated fatty acids, salts thereof, esters or amides, mono-, di- or triglycerides of fatty acids, waxes, ceramides, or cholesterol.

16. The method of claim 13 , wherein said at least one hydrophilic compound is a compound forming hydrogel.

17. The method of claim 13 , wherein said solid composition comprises a gastro-resistant coating and wherein said gastro-resistant coating is selected from among polymers of acrylic or methacrylic acid, copolymers of acrylic or methacrylic acid, cellulose acetate phthalate, hydroxybutyrate-based polymers, shellac or mixtures thereof.

18. The method of claim 13 , wherein said administration is carried out once or repeatedly.

19. The method of claim 13 , wherein the pathologies are inflammatory, ulcerative, dysplastic, pre-neoplastic or neoplastic pathologies.

20. The method of claim 13 , wherein the pathologies are cancerous or precancerous forms, polyps, pseudopolyps or different inflammatory pathologies of the small intestine and/or the large intestine.

21. The method of claim 13 , wherein said at least one dye is comprised in an amount ranging between 10 mg and 1500 mg or in an amount ranging between 50 mg and 1200 mg.

22. The method of claim 13 , wherein said at least one dye is comprised in an amount ranging between 2 mg and 1000 mg or in an amount ranging between 10 mg and 500 mg.

23. The method of claim 13 , wherein said at least one dye is comprised in an amount ranging between 20 mg and 500 mg or in an amount ranging between 25 mg and 400 mg.

24. The method of claim 13 , wherein said at least one dye is comprised in an amount equivalent to about 25 mg or in an amount equivalent to about 50 mg or in an amount equivalent to about 200 mg.

25. The method of claim 4 , wherein said at least one compound forming hydrogel is selected from among polymers or copolymers of the acrylic or methacrylic acid, alkyl vinyl polymers, alkyl celluloses, hydroxyalkyl celluloses, carboxyalkyl celluloses, modified celluloses, plurisubstituted celluloses, polysaccharides, dextrins, pectins, starches, complex starches, starch glycolate, alginic acid, synthetic rubber, natural rubber, or polyalcohol.

26. The method of claim 6 , wherein said administration is fractionated into two or more uptakes within said 24 hour period.

27. The method of claim 16 , wherein said at least one compound forming hydrogel is s

Assignees

• Cosmo Technologies Ltd
• Cosmo Tech Inc

Inventors

• Moro Luigi
• Ajani Mauro Severino
• Villa Roberto
• Celasco Giuseppe
• Repici Alessandro

Classifications

• A61K49/0089

  Particulate, powder, adsorbate, bead, sphere · CPC title

• A61B1/041

  Capsule endoscopes for imaging · CPC title

• A61K9/2846 Primary

  Poly(meth)acrylates · CPC title

• A61B1/273

  for the upper alimentary canal, e.g. oesophagoscopes, gastroscopes · CPC title

• A61K9/2059

  Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin · CPC title