Pharmaceutical Compositions Containing at Least One Protein Active Ingredient Protected From Digestive Enzymes

• US 20090176691A1
• Filed: 12/19/2008
• Published: 07/09/2009
• Est. Priority Date: 12/19/2007
• Status: Active Grant

• Current Assignee: Farid Bennis
• Original Assignee: Farid Bennis
• Inventors: Serrano, Jean Jacques, Bennis, Farid
• Granted Patent: US 8,309,123 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention relates to pharmaceutical compositions containing at least one protein active ingredient protected from digestive enzymes. Said pharmaceutical compositions contain said at least one protein active ingredient, in free form, as well as, for liquids, a system that buffers them to a pH greater than 4 and less than or equal to 8 or, for solids, a system that exerts, when they are placed in a liquid medium, a buffer effect between a pH greater than 4 and a pH less than or equal to 8.

Claims

1. A pharmaceutical composition, in liquid or solid form, for administration by oral route of at least one protein active ingredient, comprising said at least one protein active ingredient, in free form, and, for a liquid, a buffer system that buffers it to a pH greater than 4 and less than or equal to 8 or, for a solid, a buffer system that exerts, when it is placed in a liquid medium, a buffer effect between a pH greater than 4 and a pH less than or equal to 8.

2. The pharmaceutical composition according to claim 1, obtained by the formulation of said at least one protein active ingredient in free form with a system that buffers it, in liquid form, to a pH greater than 4 and less than or equal to 8 or, in solid form, with a system that exerts, when said solid form is placed in a liquid medium, a buffer effect between a pH greater than 4 and a pH less than or equal to 8.

3. The pharmaceutical composition according to claim 1, wherein the buffer pH is between 4.5 and 7.5.

4. The pharmaceutical composition according to claim 1, wherein the buffer pH is between 5 and 7.

5. The pharmaceutical composition according to claim 1, wherein the at least one protein active ingredient is selected from:

insulin and analogues and derivatives thereof,

somatotropin and derivatives thereof,

calcitonin, or

LHRH analogues.

6. The pharmaceutical composition according to claim 5, wherein said at least one protein active ingredient is insulin or analogues or derivatives thereof.

7. The pharmaceutical composition according to claim 1, wherein said buffer system is selected from phosphate, acetate, maleate, phthalate, succinate, citrate, imidazole, tetrabutylammonium, trihydroxymethylaminomethane, tris-glycine, barbitol, tris-EDTA BSA, copper sulfate or zwitterionic buffers.

8. The pharmaceutical composition according to claim 1, wherein the composition is formulated in unit form.

9. The pharmaceutical composition according to claim 1, wherein, as a liquid, it is in the form of a solution, suspension or syrup or, as a solid, in the form of tablets, notably dispersible, orodispersible or effervescent tablets, capsules, powder, effervescent powder, granules, effervescent granules or a lyophilisate.

10. The pharmaceutical composition according to claim 9, wherein it is in the form of dispersible tablets or effervescent tablets.

11. The pharmaceutical composition according to claim 1, wherein said buffer system is formulated separately from said at least one protein active ingredient.

12. A method for preparing a pharmaceutical composition, in liquid or solid form, for the oral delivery of at least one protein active ingredient, comprising the formulation of said at least one protein active ingredient in free form with a buffer system that buffers said composition, in liquid form, to a pH greater than 4 and less than or equal to 8, or in solid form, with a buffer system that exerts, when placed in a liquid medium, a buffer effect between a pH greater than 4 and a pH less than or equal to 8.

13. A method for treating a disease or disorder in a patient, the method comprising orally administering to the patient a pharmaceutical composition, in liquid or solid form, comprising at least one protein active ingredient in free form, and, for a liquid, a buffer system that buffers it to a pH greater than 4 and less than or equal to 8 or, for a solid, a buffer system that exerts, when it is placed in a liquid medium, a buffer effect between a pH greater than 4 and a pH less than or equal to 8.

14. The method according to claim 13, wherein the disease or disorder is selected from diabetes, growth inhibition, osteoporosis and prostate cancer.

15. A method for orally delivering at least one protein active ingredient, in liquid or solid form, to a patient, the method comprising orally administering to the patient at least one protein active ingredient in free form, and, for a liquid, a buffer system that buffers it to a pH greater than 4 and less than or equal to 8 or, for a solid, a buffer system that exerts, when it is placed in a liquid medium, a buffer effect between a pH greater than 4 and a pH less than or equal to 8.