Apparatus and method for preparing cosmeceutical ingredients containing epi-dermal delivery mechanisms

• US 10,307,349 B2
• Filed: 03/15/2017
• Issued: 06/04/2019
• Est. Priority Date: 12/16/2015
• Status: Active Grant

• Current Assignee: PPP&C Inc.
• Original Assignee: PPP&C Inc.
• Inventors: Richard, David A.
• Primary Examiner(s): Maewall, Snigdha
• Application Number:
  US15/460,088
• Publication Number:
  US 20170181936A1
• Time in Patent Office: 811 Days
• CPC Class Codes: A61K 2800/70 Biological properties of the composition as a whole
• CPC Class Codes: A61K 2800/805 Corresponding aspects not provided for by any of codes A61K2800/81 - A61K2800/95
• CPC Class Codes: A61K 8/06 Emulsions
• CPC Class Codes: A61K 8/14 Liposomes; Vesicles
• CPC Class Codes: A61K 8/416 Quaternary ammonium compounds A61K8/35 takes precedence
• CPC Class Codes: A61K 8/553 Phospholipids, e.g. lecithin
• CPC Class Codes: A61K 8/63 Steroids; Derivatives thereof
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61K 8/9789 Magnoliopsida [dicotyledons]
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations

Abstract

The skin serves as a barrier that protects the body from the external environment and prevents water loss. This barrier function also prevents most hydrophilic or hydrophobic and large molecular weight ingredients (>500 kDa) from penetrating intact skin. Until recently, methods to increase stratum corneum permeability were generally not effective enough to make the stratum corneum so permeable that the barrier posed by the viable epidermis mattered. However, that has now changed with the development of the present embodiment'"'"'s physical methods and highly optimized chemical formulations, such that we revisited the permeability of the full epidermis with the example embodiment'"'"'s constructs and not focus only on the stratum corneum. This example embodiment therefore tests the hypothesis that the viable epidermis offers a significant permeability barrier to both small molecules and macromolecules that becomes the rate limiting step.

Claims

1. A method for the construction of cosmeceutically bioactive compositions including elastic niosome vesicle epi-dermal delivery vehicles without use of supercritical CO₂ and in a continuously operating process, the method comprising:

forming a liposome solution or mixture of cosmeceutically benevolent phospholipids, the solution being hydrophobic or hydrophilic, the solution including an ingredient from the group consisting of a natural ingredient and a synthetic ingredient, the solution having an aqueous phase;

removing any constituent attributes of water-insolubility from the solution, while operating under conditions to preserve activity of labile biomolecules;

loading the liposome solution and desired hydrophobic bio-actives into an organic solvent residing in a pressure reactor, the pressure reactor having been previously driven to a working temperature less than 31.1°

C.;

pressurizing the reactor with compressed CO₂ until reaching a working pressure less than 73.8 bar to produce a resulting CO₂-expanded solution, the reactor maintaining a pressure and temperature to prevent the CO₂ from going supercritical; and

depressurizing the resulting CO₂-expanded solution over an aqueous phase to form vesicular conjugates, the resulting solution containing water soluble cationic or non-ionic surfactants and hydrophilic or hydrophobic bio-actives, wherein an emulsion further comprises a water-soluble or fat-soluble cosmetic or cosmeceutical active ingredient.

2. The method of claim 1 wherein the phospholipids are selected from the group consisting of:

a nonionic amphiphilic lipid, an ionic amphiphilic lipid, a mixture of nonionic lipids, and an ionic lipid.

3. The method of claim 1 wherein the phospholipids are of the phosphate group of phosphatidylcholine (PC) amphiphilic molecules, having a polar head group and a lipophilic tail, and are esterified with an additional alcohol of choline possessing a zwitterionic isoelectric point and are negatively charged at higher pH values and positively charged at lower pH values.

4. The method of claim 1 wherein the phospholipids are of the phosphate group phosphatidylethanolarnine (PE), and are esterified with an additional alcohol of ethanolarnine and are a neutral charged zwitterionic.

5. The method of claim 1 wherein the phospholipids are of the phosphate group phosphatidylglycerol (PG) with glycerol being anionic in charge.

6. The method of claim 1 wherein the phospholipids are of the phosphate group consisting of a ceramide unit with a phosphorylcholine moiety attached, and a sphingolipid analogue of phosphatidylchol, or sphingomyelin, or ceramide phosphorylcholine.

7. The method of claim 1 wherein the phospholipids are amphiphilic liposomes wherein the molar ratio of the mixture of cholesterol and at least one neutral or zwitterionic lipid is between 8 and 0.15.

8. The method of claim 1 wherein the phospholipids include at least one non-ionic amphiphilic lipid being an ester of at least one polyol, said ester being a polyethylene glycol containing from 0.5 to 70 ethylene oxide units, sorbitan, glycerol containing from 1 to 35 ethylene oxide units, polyglycerol containing from 1 to 18 glycerol units, or a fatty acid containing at least one saturated or unsaturated, linear or branched, C8-C22 alkyl chain.

9. The method of claim 1 wherein at least one cationic amphiphilic lipid is present in the liposome solution or mixture in a concentration ranging from 0.5 to 65% by weight with respect to the total weight of the amphiphilic lipid phase.

10. The method of claim 1 including using a formation of unilamellar vesicles having one lipid bilayer between 50-250 nm enclosing a large aqueous core, and multilamellar vesicles having two or more concentric lipid bilayers between 1-5 μ

m.

11. The method of claim 1 including using cholesterol to anchor phosphate group phosphatidylcholine (PC) amphiphilic molecules, the phosphate group phosphatidylethanolarnine (PE) molecules, and the phosphate group phosphatidylglycerol (PG) molecules.

12. The method of claim 1 including using an amphiphilic liposome having neutral lipids wherein said neutral lipids are selected from the group consisting of cholesterol or mixtures of cholesterol and at least one neutral or zwitterionic lipid.

13. The method of claim 1 including using an amphiphilic liposome having phosphatidylcholine selected from DMPC, DPPC, DSPC, POPC, DOPC, soy bean PC or egg PC.

14. The method of claim 1 including using an amphiphilic liposome having K neutral of a mixture of cholesterol and at least one neutral or zwitterionic lipids.

15. The method of claim 1 including using an amphiphilic liposome having a mixture of cholesterol and at least one neutral or zwitterionic lipid selected from the group consisting of:

cholesterol/phosphatidylcholine, cholesterol/phosphatidylethanolamine, and cholesterol/phosphatidylethanolamine/ phosphatidylcholine.

16. The method of claim 1 including using an amphiphilic liposome having a mixture of lipid components with amphiphilic properties and wherein said mixture of lipid components comprises at least one pH responsive component.

17. The method of claim 1 including using an amphiphilic liposome that encapsulates at least one active agent.

18. The method of claim 1 including using an amphiphilic liposome wherein at least 80 wt. percentage of an active agent is disposed inside said liposomes.

19. The method of claim 1 including liposomes being non-encapsulated active agents.

20. The method of claim 1 including forming a cosmeceutical composition comprising active agent-loaded amphiphilic liposomes and a cosmeceutically acceptable vehicle therefor.

21. The method of claim 1 including using amphiphilic liposomes in vitro, in vivo or ex-vivo transfection of cells.