Absorption enhancers such as e.g. BHT, BHA or propyl gallate

• US 7,651,995 B2
• Filed: 04/15/2004
• Issued: 01/26/2010
• Est. Priority Date: 04/15/2003
• Status: Expired due to Fees

• Current Assignee: Axcess Limited
• Original Assignee: Axcess Limited
• Inventors: New, Roger R. C.
• Primary Examiner(s): AUDET, MAURY A
• Application Number:
  US10/553,324
• Publication Number:
  US 20060223740A1
• Time in Patent Office: 2,112 Days
• Field of Search: None
• US Class Current: 514/1.1
• 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 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/28 Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 5/48 of the pancreatic hormones

Abstract

The invention provides a pharmaceutical composition comprising a mixture of (a) an active macromolecular principle, and (b) an aromatic alcohol absorption enhancer chosen from butylated hydroxy toluene, butylated hydroxy anisole and analogues and derivatives thereof, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active macromolecular principle, and further comprises a pharmaceutical composition comprising a mixture of (a) an active macromolecular principle, (b) an aromatic alcohol absorption enhancer chosen from propyl gallate, butylated hydroxy toluene, butylated hydroxy anisole and analogues and derivatives thereof, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active macromolecular principle, and (c) a solubilisation aid capable of increasing the solubility of the aromatic alcohol absorption enhancer in aqueous media.

Claims

1. A method of enhancing the absorption of an active macromolecular principle which is a polypeptide or protein, polynucleotide or polysaccharide in a patient, which method comprises orally administering to said patient a composition comprising an aromatic alcohol absorption enhancer chosen from propyl gallate, butylated hydroxy toluene (BHT), butylated hydroxy anisole (BHA) and analogues and derivatives thereof, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active macromolecular principle, wherein the composition is coated with an enteric coating which becomes permeable at a pH of from 3 to 7, and wherein when the aromatic alcohol is propyl gallate or an analogue or derivative thereof, the composition further comprises a solubilization aid capable of increasing the solubility of the aromatic alcohol absorption enhancer in aqueous media.

2. A method according to claim 1, wherein the composition enhances the absorption of the active macromolecular principle across the intestinal wall.

4. A method according to claim 2, wherein the composition comprises less than 5% by weight of water.

5. A method according to claim 2, wherein the solubilization aid is selected from a conjugated bile acid or salt, benzylalcohol, phenylethanol, phenoxylethanol, transcutol and isopropanol.

6. A method according to claim 2, wherein the composition is comprised in a medicament, which medicament is provided in the form of a solution, as a microparticulate dispersion or as a solid.

7. A method according to claim 2, wherein the active macromolecular principle is a polypeptide or protein.

8. A method according to claim 7, wherein the active macromolecular principle is insulin, calcitonin, growth hormone, parathyroid hormone, erythropoeitin, GLP1 or GCSF, or a derivative or analogue thereof, either synthetic or from natural sources, conforming to structures derived from either human or animal origin.

9. A method according to claim 8, wherein the active macromolecular principle is insulin, calcitonin, parathyroid hormone or a derivative or analogue thereof, either synthetic or from natural sources, conforming to structures derived from either human or animal origin.

10. A method according to claim 9, wherein the active macromolecular principle is insulin or a derivative or an analogue thereof, either synthetic or from natural sources, conforming to structures derived from either human or animal origin and an insulin sensitizing agent is also present.

11. A method according to claim 2, wherein the active macromolecular principle is a polynucleotide which is single, double or triple-stranded RNA or a polysaccharide which is heparin.

12. A method according to claim 11, wherein the polynucleotide is double-stranded RNA.

13. A method according to claim 1, wherein the active macromolecular principle has a molecular weight of over 2000 Da.

14. A method according to claim 1, wherein the active macromolecular principle has a molecular weight of over 3000 Da.

3. A method of enhancing the absorption of an active macromolecular principle which is a polypeptide or protein, polynucleotide or polysaccharide in a patient, which method comprises orally administering to said patient an aromatic alcohol chosen from propyl gallate, butylated hydroxy toulene, butylated hydroxy anisole and analogues and derivatives thereof together with a solubilization aid capable of increasing the solubility of the aromatic alcohol absorption enhancer in aqueous media.