APPARATUS AND METHOD FOR PREPARING COSMECEUTICAL INGREDIENTS CONTAINING EPI-DERMAL DELIVERY MECHANISMS

• US 20190314251A1
• Filed: 05/27/2019
• Published: 10/17/2019
• Est. Priority Date: 12/16/2015
• Status: Abandoned Application

• Current Assignee: PPP&C Inc.
• Original Assignee: PPP&C Inc.
• Inventors: Richard, David A.
• Application Number:
  US16/423,099
• Publication Number:
  US 20190314251A1
• Time in Patent Office: 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 liposome or elastic niosome vesicle epi-dermal delivery vehicles without use of supercritical CO₂ and in a continuously operating process, the method comprising:

forming a solution or mixture of cosmeceutically benevolent phospholipids, the solution being a hydrophobic or hydrophilic, natural or synthetic ingredient, with an aqueous phase;

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

loading the solution of the membrane lipid or niosome components and desired hydrophobic bio-actives into an organic solvent residing in a pressure reactor, the pressure reactor having been previously driven to a pre-determined working temperature;

pressurizing the reactor with compressed CO₂ until reaching a pre-determined working pressure; 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.

2. The method of claim 1 wherein the lipid is selected from a nonionic amphiphilic lipid, an ionic amphiphilic lipid, or a mixture of a nonionic lipid and an ionic lipid.

3. The method of claim 1 wherein the membrane lipid is a membrane phospholipid of the phosphate group phosphatidylcholine (PC) amphiphilic molecules, comprising a polar head group and a lipophilic tail, and is 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 membrane lipid is a membrane phospholipid of the phosphate group phosphatidylethanolarnine (PE), and is esterified with an additional alcohol of ethanolamine and is a neutral charged zwitterionic.

5. The method of claim 1 wherein the membrane lipid is a membrane phospholipid of the phosphate group phosphatidylglycerol (PG) with glycerol being anionic in charge.

6. The method of claim 1 wherein the membrane lipid is a membrane phospholipid 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 membrane lipid is an amphiphilic liposome 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 membrane lipid includes at least one non-ionic amphiphilic lipid is (a) 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 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 wherein an emulsion further comprises a water-soluble or fat-soluble cosmetic or cosmeceutical active ingredient.

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

m.

12. The method of claim 1 wherein cholesterol is used to anchor phosphate group phosphatidylcholine (PC) amphiphilic molecules, the phosphate group phosphatidylethanolarnine (PE) molecules, and the phosphate group phosphatidylglycerol (PG) molecules.

13. The method of claim 1 wherein an amphiphilic liposome is comprised of neutral lipids wherein said neutral lipids are selected from the group comprising cholesterol or mixtures of cholesterol and at least one neutral or zwitterionic lipid.

14. The method of claim 1 wherein an amphiphilic liposome includes phosphatidylcholine selected from DMPC, DPPC, DSPC, POPC, DOPC, soy bean PC or egg PC.

15. The method of claim 1 wherein an amphiphilic liposome includes K (neutral) of a mixture of cholesterol and at least one neutral or zwitterionic lipids is less than 0.45, and less than 0.2 and less than 0.1.

16. The method of claim 1 wherein an amphiphilic liposome includes 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.

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

18. The method of claim 1 wherein an amphiphilic liposome encapsulates at least one active agent.

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

20. The method of claim 1 wherein the liposomes comprise non-encapsulated active agents.

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

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