Ulcer prevention and treatment composition

• US 5,651,987 A
• Filed: 08/27/1993
• Issued: 07/29/1997
• Est. Priority Date: 12/17/1991
• Status: Expired due to Fees

• Current Assignee: Biovail Laboratories International Srl (Bausch Health Cos., Inc.)
• Original Assignee: Fuisz Technologies Limited (Bausch Health Cos., Inc.)
• Inventors: Fuisz, Richard C.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US08/113,485
• Time in Patent Office: 1,432 Days
• Field of Search: 424/484, 424/485, 424/487, 424/488, 424/499, 424/500, 424/507, 514/925
• US Class Current: 424/488
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7135 Compounds containing heavy metals
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Abstract

Anti-ulcer compositions are disclosed having therapeutic agents dispersed in a soluble matrix formed by melt spinning the therapeutic agent with a carrier and hydrogel. Methods of treating ulcer-bearing tissue and preparing the matrix are also disclosed. One embodiment includes use of gastric irritating bio-affecting agents in which case the composition is preventative as well as therapeutic.

Claims

1. An anti-ulcer composition having rapid delivery and enhanced adherence to ulcer-bearing tissue comprising:

a solid matrix having suspended therein an anti-ulcer medicament, said matrix formed by flash-flow melt-spinning a mixture of

i) a melt-spinnable carrier material present in an amount sufficient to form a flash-flow melt-spun matrix when said anti-ulcer medicament is dispersed therein;

ii) an anti-ulcer medicament present in an amount sufficient to achieve a therapeutic effect; and

iii) a hydrogel in addition to said carrier material, said hydrogel being selected from the group consisting of gums, cellulose, pectins, gelatin, polycarbophil, alginate and mixtures thereof to provide mucosal adherence.

2. The composition of claim 1, wherein said anti-ulcer medicament is sucralfate.

3. The composition of claim 1, wherein said anti-ulcer medicament is selected from the group consisting of cimetidine, ranitidine, nizatidine, famotidine, omeprazole and mixtures thereof.

4. The composition of claim 1, wherein said medicament is present in an amount of from about 0.1 to about 50% by weight of said matrix.

5. The composition of claim 4, wherein said medicament is present in an amount of from about 0.1 to about 20% by weight of said matrix.

6. The composition of claim 1, wherein said carrier material is selected from the group consisting of maltodextrins, corn syrup solids, polydextrose, maltooligosaccharides and mixtures thereof.

7. The composition of claim 6, wherein said hydrogel is selected from the group consisting of xanthan gum, guar gum, carrageenan gum, gum tragacanth, sodium alginate, gum karaya, locust bean gum, gum acacia and mixtures thereof.

8. The composition of claim 7 wherein said hydrogel is present in an amount of from about 0.2 to about 4% by weight of said matrix.

9. The composition of claim 8 wherein said hydrogel is present in an amount of from about 0.8 to about 2.5% by weight of said matrix.

10. The composition of claim 1 wherein said hydrogel is cellulose or a cellulose derivative.

11. The composition of claim 10, wherein said hydrogel hydroxypropylmethyl cellulose is HPMC.

12. The composition of claim 11, wherein said anti-ulcer medicament is sulcralfate.

13. The composition of claim 10, wherein said hydrogel is xanthan gum.

14. The composition of claim 1 which further comprises a gastric-irritating bio-affecting agent.

15. The composition of claim 14, wherein said bio-affecting agent is a non-steroidal anti-inflammatory (NSAI) agent.

16. The composition of claim 15 wherein said non-steroidal anti-inflammatory (NSAI) is selected from the groups consisting of salicylate NSAI agents, acetic acid NSAI agents, oxicam NSAI agents, oxidole NSAI agents and mixtures thereof.

17. The composition of claim 14 wherein said bio-affecting agent is a steroid.

18. The composition of claim 17 wherein said steroid is selected from the group consisting of andrenocorticoids and corticotropins.

19. The composition of claim 1 wherein an antacid is included in said matrix by subjecting said antacid to flash-flow along with said medicament and said mixture.

20. The composition of claim 19 which further comprises a non-steroidal anti-inflammatory (NSAI) agent subjected to flash-flow with said antacid and said medicament and said mixture.

21. An anti-ulcer medication comprising:

a) an anti-ulcer medicament dispersed in a first matrix formed by subjecting to flash-flow condition a first feedstock comprising said medicament and a mixture comprising a saccharide carrier material and a hydrogel selected from the group consisting of gums, celluloses, pectins, gelatin, polycarbophil, alginate and mixtures thereof to provide mucosal adherence;

b) an antacid agent dispersed in a second matrix formed by subjecting flash-flow conditions a second feedstock comprising said antacid and a carrier material comprising a saccharide.

22. The medication of claim 21 wherein said first feedstock further comprises a non-steroidal anti-inflammatory (NSAI) agent.

23. The medication of claim 21 wherein said second feedstock further comprises a non-steroidal anti-inflammatory (SAI) agent.

24. A pharmaceutical composition having rapid delivery and enhanced adherence to mucosal tissue comprising:

a solid matrix having suspended therein a medicament, said matrix formed by flash-flow melt-spinning a mixture of

i) a melt-spinnable carrier comprising a saccharide present in an amount sufficient to form a flash-flow melt-spun matrix when said medicament is dispersed therein;

ii) a medicament present in an amount sufficient to achieve a therapeutic effect; and

iii) a hydrogel in addition to said carrier, said hydrogel being selected from the group consisting of gums, celluloses, pectins, gelatin, polycarbophil, alginate and mixtures thereof to provide mucosal adherence properties.

25. The pharmaceutical composition of claim 24 wherein the medicament is a drug which acts systematically.

26. The pharmaceutical composition of claim 25 wherein the drug is selected from the group consisting of anti-infectives and anti-lipid agents.

27. The pharmecutical composition of claim 24 wherein the carrier is selected from the group consisting of maltodextrins, corn syrup solids, polydextroses, maltooligo-saccharides and mixtures thereof.

28. The pharmecutical composition of claim 24 wherein said hydrogel is selected from the group consisting of xanthan gum, guar gum, carrageenan gum, gum tragacanth, sodium alginate, gum karaya, locus bean gum, gum acacia and mixtures thereof.

29. The composition of claim 28 wherein said hydrogel is present in an amount of from about 0.2 to about 4% by weight of said matrix.

30. The composition of claim 24, wherein said solid matrix further comprises an oleaginous substance in an amount sufficient to provide even distribution of said medicament.

31. The composition of claim 30 wherein said oleaginous substance is selected from the group consisting of corn oil, sunflower oil, olive oil, vegetable oils and mixtures thereof.

32. The pharmaceutical composition of claim 24 wherein said hydrogel is cellulose or a cellulose derivative.

33. The composition of claim 32 wherein said cellulose is hydroxypropylmethyl cellulose HPMC.

34. The pharmacutical composition of claim 32 wherein the cellulose is selected from the group consisting of hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, carboxymethylcellulose, hydroxymethylcellulose and mixtures thereof.

35. The pharmacutical composition of claim 24 wherein said hydrogel is xanthan gum.