Liposome-containing cosmetic composition

Abstract

Cosmetic or cosmeceutical compositions (or formulations) are provided that include a liposome or liposomes and a cosmetically acceptable carrier, at least some of which are formed from one or more bilayer-forming lipids and polymeric compounds as described and defined herein. Skin care products containing the cosmetic or cosmeceutical compositions and uses thereof are also provided.

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 63 / 402,088, filed August 30, 2022.

[0002] This application is also related to U.S. Provisional Patent Application No. 63 / 402,097, filed August 30, 2022 by the present assignee, the contents of which are incorporated by reference as if set forth in their entirety herein.

[0003] In some embodiments thereof, the present invention relates to cosmetics, and more particularly, but not exclusively, to cosmetic compositions and products incorporating therein liposomes formed from lipid bilayer-forming materials and polymeric materials. [Background technology]

[0004] Human skin, the largest organ of the human body, protects against germs, regulates body temperature, and enables the sense of touch (tactile sensation). Three layers of tissue make up the skin: the subcutaneous tissue (bottom layer), the dermis (middle layer), and the epidermis (top layer). The stratum corneum is the skin layer targeted by many cosmetic products.

[0005] Ceramides are the main components of the stratum corneum, the epidermal layer of human skin. Together with cholesterol and saturated fatty acids, ceramides create a water-impermeable protective layer that prevents excessive water loss through evaporation and a barrier against microbial invasion. The stratum corneum is composed of 50% ceramides, 25% cholesterol, and 15% free fatty acids. These lipids form a bilayer 4-5 nm thick. A particular group of ceramides contains a C36 side chain, which extends into adjacent bilayers, thereby "nailing" them together. An important component of the extracellular lipid lamellae of the stratum corneum are very long-chain (C28-C36) ceramides. With aging, the human stratum corneum experiences a decline in ceramides and cholesterol. See, for example, Hill JR and Wertz PW (2009) Lipids, 44 (3): 291-295, Garidel P et al. (2010) Biophysical Chemistry, 150 (1-3): 144-156, Feingold KR (2007) Journal of Lipid Research, 48 (12): 2531-2546, Jennemann R et al. (2012) Human Molecular Genetics. 21 (3): 586-608, and Popa I et al. (2010) International Journal of Cosmetic Science, 32 (3): 225-232.

[0006] The hydration level of the skin, especially the stratum corneum (the outermost barrier of the epidermis), is directly related to its appearance (i.e., fineness of texture) and is also considered an indicator of its health. Furthermore, dry skin is more vulnerable to external aggressions. Furthermore, skin moisture content is an important factor for skin permeability to topically applied substances, and increased moisture in the stratum corneum generally enhances the transdermal influx of substances [Esposito et al. (2007) International Journal of Cosmetic Science, 29(1), pp.39-47]. Therefore, maintaining the moisture content of the skin barrier is essential for maintaining the function and aesthetic appearance of the skin.

[0007] Lipids play a crucial role in creating and maintaining the barrier function of the stratum corneum. During the transformation of keratinocytes into corneocytes and their migration to the uppermost layer of the skin, a great deal of anabolic and catabolic activity of lipid materials occurs. One consequence of phospholipase activity in the stratum corneum is a dramatic decrease in the proportion of phospholipids in the lipid composition from the basal layer (approximately 50%) to the stratum corneum (less than 5%), and a significant increase in the fatty acid content of the stratum corneum.

[0008] Research has shown that the stratum corneum is not itself a uniform matrix; rather, it forms a highly heterogeneous structure, containing a variety of other biologically active substances in addition to corneocytes and multilamellar lipid layers.

[0009] Lipids are biomolecules that are soluble in non-polar solvents, which are typically hydrocarbons used to dissolve essentially water-immiscible substances, including fatty acids, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E, and K), monoglycerides, diglycerides, triglycerides, and phospholipids.

[0010] Fatty acids and lipids are biocompatible and have the ability to protect and improve skin barrier and appearance, and are therefore used as ingredients in various cosmetic products.For example, lipids have a strong adhesive force to the skin, leading to the formation of a film on the skin, thus helping to repair defects in the natural skin barrier and strengthen the thin natural lipid film.This re-creation of the skin barrier provides an anti-pollution effect.In addition, lipids lead to the formation of a particle film occlusion on the skin, thereby increasing skin moisture retention and maintaining appropriate living conditions for the basal keratinocyte cells that make up most of the epidermal layer.

[0011] In cosmetic products, biodegradable phospholipids can be used as in the formulation of suspensions, oil-in-water and water-in-oil emulsions, and mixed micelles.

[0012] Phospholipids are a class of lipids consisting of a hydrophilic "head" bearing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). In typical membrane phospholipids, such as phosphatidylcholine (PC), the phosphate group is further esterified with an additional alcohol, whereas in phosphatidylethanolamine (PE), it is esterified with ethanolamine. Depending on the structure of the polar region and the pH of the medium, PC and PE are zwitterionic and have a neutral charge at a pH of about 7, while other phospholipids can be negatively charged.

[0013] When mixed with aqueous phase, phospholipids can form various structures depending on the number and type of fatty acids esterified to the glycerol backbone and the surface area ratio occupied by the hydrophilic and lipophilic parts of the phospholipid molecule.Cylindrical-shaped diacyl phospholipids (such as PC and PE) are typically organized as lipid bilayers (liposomes) with their hydrophobic tails aligned opposite each other and their hydrophilic head groups facing water on both sides.The bilayer membrane of such liposomes resembles the basic structure of cell membranes, so liposomes are biocompatible and have beneficial interactions with skin cells.

[0014] Phospholipids are typically used in cosmetics as surfactants (e.g., emulsifiers) and / or to enhance skin penetration, and are also used as bilayer lipid forming materials.

[0015] Phospholipid polymers have been used to modify the surface structure of cell membranes, and are attractive raw materials in cosmetics because they inhibit protein adsorption, are highly biocompatible, and can maintain the moisture content of the skin surface.

[0016] 2-Methacryloyloxyethyl phosphorylcholine (MPC) is a biomimetic, biocompatible material with a structure similar to that of skin cell membranes. It is used in a variety of fields, including cosmetics and personal care products, contact lenses, contact lens storage and cleaning solutions, medical devices, textiles, and cell culture equipment.

[0017] Copolymers made of MPC and hydrophobic methacrylate monomers, for example, characterized by alkyl pendant groups (e.g., butyl or higher alkyl), including block copolymers, have been described to improve the skin's moisturizing ability and have been incorporated into various cosmetic formulations.

[0018] WO 2017 / 109784 describes polymeric compounds comprising a lipid moiety and an ionic polymer moiety, such as pMPC (poly(O-(2-methacryloyloxyethyl)phosphorylcholine)), as well as bilayers and liposomes comprising such polymeric compounds in combination with bilayer-forming lipids. Bilayers and / or liposomes comprising such polymeric compounds are said to be useful for reducing the coefficient of friction of surfaces and / or inhibiting biofilm formation.

[0019] Further background art includes WO 2016 / 051413 and WO 2018 / 150429, FR 2774286, EP 3662890, JP 6679308, and U.S. Pat. Nos. 5,744,145, 11,260,021, 5,653,966, and 8,956,668. Summary of the Invention

[0020] According to an aspect of some embodiments of the present invention, there is provided a cosmetic or cosmeceutical composition (or formulation) comprising liposomes and a cosmetically acceptable carrier, wherein the liposomes are a) at least one bilayer-forming lipid, and b) a polymeric compound having the general formula I A cosmetic or cosmeceutical composition (or formulation) is provided, comprising: [ka] (In the formula, m is zero or a positive integer; n is an integer of at least 2, at least 5, preferably at least 10 (e.g., from 10 to 200); Y is a backbone unit that forms the polymer backbone of the polymer compound, L is absent or a linking moiety; Z has the general formula II, [ka] (In the formula, The wavy lines represent the points of attachment to the corresponding Y backbone units, A is a substituted or unsubstituted hydrocarbon; B is an oxygen atom or is absent; R1 to R3 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heteroalicyclic, aryl, and heteroaryl. X is a lipid moiety represented by formula IV. [ka] (In the formula, F1, F2, F3, and F4 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, acyl, alkoxy, thioalkoxy, carboxy, and thiocarboxy, and at least one of F1, F2, F3, and F4 is not hydrogen and is at least 10 carbon atoms in length; J is -OP(=O)(OH)-O- or absent; K is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length or is absent; M is a linking group selected from the group consisting of -O-, -S-, amino, sulfinyl, sulfonyl, phosphate, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, urea, thiourea, carbamyl, thiocarbamyl, amido, carboxy, and sulfonamido, or is absent; and Q is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length or is absent; When M is not present, Q is not present, and when J is not present, M is not present; provided that when J is -OP(=O)(OH)-O-, then M is other than an amide and / or Q includes an aryl moiety.

[0021] According to some of the optional embodiments described herein, at least one of F1, F2, F3, and F4 is an alkoxy, thioalkoxy, acyl, or carboxy at least 10 carbon atoms in length.

[0022] According to some of the optional embodiments described herein, at least one of F1, F2, F3, and F4 is derived from a fatty acid selected from the group consisting of lauroyl, myristoyl, palmitoyl, stearoyl, palmitoleoyl, oleoyl, and linoleoyl.

[0023] According to some of the embodiments described herein, M is carboxy.

[0024] According to some of the embodiments described herein, K is alkyl.

[0025] According to some of the embodiments described herein, J is -P(=O)(OH)-O-, M is an amide, and Q is a hydrocarbon substituted with at least one aryl (e.g., phenyl).

[0026] According to some of the embodiments described herein, Q is methylene substituted with at least one aryl.

[0027] According to some of the optional embodiments described herein, J is absent.

[0028] According to some of the optional embodiments described herein, J and K are each absent.

[0029] According to some of the embodiments described herein, J and K are each absent and M is carboxy.

[0030] According to some of the embodiments described herein, at least one or at least two of F1, F2, F3, and F4 are each independently thioalkoxy.

[0031] According to some of the embodiments described herein, at least one or at least two of F1, F2, F3, and F4 are each independently carboxy.

[0032] According to some of the optional embodiments described herein, at least one or both of F1 and F2 is carboxy, and at least one of F3 and F4 is alkyl.

[0033] According to some of the optional embodiments described herein, Y is a substituted or unsubstituted alkylene unit.

[0034] According to some of the optional embodiments described herein, Y is a substituted or unsubstituted ethylene unit.

[0035] According to some of the embodiments described herein, Y has the formula -CR4R5-CR6D-; When Y is a backbone unit that is not bonded to L or Z, D is R7; When Y is a backbone unit attached to L or Z, D is a covalent bond or linking group attaching Y to L or Z, the linking group being selected from the group consisting of -O-, -S-, alkylene, arylene, sulfinyl, sulfonyl, phosphate, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, urea, thiourea, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, and amino; and R4-R7 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, cyano, nitro, azido, azo, phosphate, phosphonyl, phosphinyl, oxo, carbonyl, thiocarbonyl, urea, thiourea, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, and amino.

[0036] According to some of the optional embodiments described herein, R4-R7 are each independently selected from hydrogen and alkyl.

[0037] According to some of the embodiments described herein, R4 and R5 are each hydrogen.

[0038] According to some of the embodiments described herein, R6 is hydrogen.

[0039] According to some of the optional embodiments described herein, the linking group is selected from the group consisting of -O-, -C(=O)O-, -C(=O)NH-, and phenylene.

[0040] According to some of the embodiments described herein, the linking group is -C(=O)O-.

[0041] According to some of the optional embodiments described herein, L is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length.

[0042] According to some of the optional embodiments described herein, L is a substituted or unsubstituted ethylene group.

[0043] According to some of the embodiments described herein, B is an oxygen atom.

[0044] According to some of the optional embodiments described herein, A is a substituted or unsubstituted hydrocarbon of 1 to 4 carbon atoms in length.

[0045] According to some of the optional embodiments described herein, A is a substituted or unsubstituted ethylene group.

[0046] According to some of the embodiments described herein, R1-R3 are each independently hydrogen or C 1~4 - alkyl.

[0047] According to some of the optional embodiments described herein, R1-R3 are each methyl.

[0048] According to some of the optional embodiments described herein, n is in the range of 10-200.

[0049] According to some of the embodiments described herein, n is at least 30.

[0050] According to some of the optional embodiments described herein, n is in the range of 30-70 or 30-60.

[0051] According to some of the embodiments described herein, n is at least 50 or at least 60.

[0052] According to some of the optional embodiments described herein, n is in the range of 50-150, or 60-150, or 50-80, or 60-80.

[0053] According to some of the optional embodiments described herein, n is in the range of 60-80.

[0054] According to some of the embodiments described herein, n is at least 80, or is in the range of 80-150 or 80-120.

[0055] According to some of the optional embodiments described herein, m is in the range of 0-50.

[0056] According to some of the optional embodiments described herein, at least some of the backbone units Y, L and / or Z comprise at least one targeting moiety as described herein.

[0057] According to some of the embodiments described herein, the molar ratio of bilayer-forming lipid to polymeric compound is in the range of 5:1 to 5,000:1, or 10:1 to 1,000:1, or 10:1 to 100:1, or 10:1 to 50:1, or 100:1 to 200:1. According to some of the embodiments described herein, at least some of the liposomes comprise a plurality of liposomes as described herein for any corresponding embodiment and any combination thereof.

[0058] According to some of the embodiments described herein, the polydispersity index of the liposomes is less than 1, or less than 0.8, or less than 0.6.

[0059] According to some of the embodiments described herein, the average diameter of the liposomes is within the range of 50 to 5,000 nm, or 500 to 5,000 nm, or 500 to 3,500 nm, or 200 to 2,000 nm, or 200 to 1,000 nm, or 400 to 1,000 nm, or 400 to 800 nm.

[0060] According to some of the optional embodiments described herein, the amount of bilayer-forming lipid in the composition is in the range of 0.1 to 5% by weight of the total weight of the composition.

[0061] According to some of the optional embodiments described herein, the weight ratio of bilayer-forming lipid to polymeric compound is within the range of 1:1 to 3,000:1, or 1:1 to 1,000:1, or 1:1 to 500:1, or 1:1 to 300:1, or 1:1 to 100:1, or 1:1 to 50:1, or 5:1 to 50:1, or 5:1 to 30:1.

[0062] According to some of the optional embodiments described herein, the cosmetic or cosmeceutical composition is formulated for topical application.

[0063] According to some of the embodiments described herein, the carrier comprises an aqueous liquid.

[0064] According to some of the optional embodiments described herein, the liposome or liposomes are contained in an aqueous liquid.

[0065] According to some of the optional embodiments described herein, the carrier forms the composition in the form of a cream, ointment, gel, lotion, soap, shampoo, water-in-oil emulsion, oil-in-water emulsion, water-in-oil-in-water emulsion, oil-in-water-in-oil emulsion.

[0066] According to some of the optional embodiments described herein, the total amount of bilayer-forming lipids and polymeric compounds is in the range of 0.1 to 10 or 0.1 to 5 wt. % of the total weight of the composition.

[0067] According to some of the optional embodiments described herein, the composition is in the form of a gel, and the total amount of bilayer-forming lipids and polymeric compounds is in the range of 1 to 10 or 1 to 5 wt. % of the total weight of the composition.

[0068] According to some of the optional embodiments described herein, the composition is in the form of a cream or emulsion, and the total amount of bilayer-forming lipids and polymeric compounds is in the range of 0.1 to 5 or 0.1 to 1 wt. % of the total weight of the composition.

[0069] According to an aspect of some embodiments of the present invention, there is provided a skin care product comprising a cosmetic or cosmeceutical composition as described herein for any corresponding embodiment and any combination thereof.

[0070] According to an aspect of some embodiments of the present invention, there is provided a composition as described herein for any corresponding embodiment and any combination thereof or a skin care product as described herein for any corresponding embodiment and any combination thereof, for hydrating skin.

[0071] According to an aspect of some embodiments of the present invention, there is provided a composition as described herein for any corresponding embodiment and any combination thereof or a skin care product as described herein for any corresponding embodiment and any combination thereof for the treatment of damaged keratinous tissue.

[0072] According to an aspect of some embodiments of the present invention, there is provided a method of administering cosmetic care to a subject in need thereof, the method comprising applying an effective amount of a composition as described herein for any corresponding embodiment and any combination thereof or a skin care product as described herein for any corresponding embodiment and any combination thereof to the skin of the subject, thereby administering the cosmetic care.

[0073] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of this invention, exemplary methods and / or materials are described below. In case of conflict, the present patent specification, including definitions, will control. Furthermore, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0074] Some embodiments of the present invention are herein described, by way of example only, with reference to the accompanying drawings. Reference will now be made specifically in detail to the drawings, and it will be emphasized that the specific details shown are by way of example and are for the purpose of describing embodiments of the invention. In this regard, the description taken together with the drawings will make apparent to those skilled in the art how embodiments of the invention may be practiced. [Brief explanation of the drawings]

[0075] [Figure 1] 1 presents a scheme illustrating an exemplary synthetic protocol for preparing an exemplary polymeric compound (lipid-polymer conjugate, LPC) according to some embodiments of the present invention. [Figure 2-1] Graphs are presented showing the corneometry (water retention) of IM22-777 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (FIG. 2A) and various lipid standards (IM22-743 and IM22-736) (FIG. 2B). [Figure 2-2] 1 presents the TEWL of IM22-777 as a function of time in comparison with various standards. [Figure 3-1] Graphs are presented showing the corneometry (water retention) of IM22-778 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (FIG. 3A) and various lipid standards (IM22-743 and IM22-736) (FIG. 3B). [Figure 3-2] The TEWL of IM22-778 as a function of time in comparison with various standards is presented. [Figure 4-1] Graphs are presented showing the corneometry (water retention) of IM22-754 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (FIG. 4A) and various lipid standards (IM22-743 and IM22-736) (FIG. 4B). [Figure 4-2] The TEWL of IM22-754 as a function of time in comparison with various standards is presented. [Figure 5]Graphs are presented showing the corneometry (water retention) of IM22-744 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (FIG. 5A) and various lipid standards (IM22-743 and IM22-736) (FIG. 5B). [Figure 6] 1 presents a graph showing the corneometry (water retention) of IM22-732 gel formulations as a function of time in comparison to various lipid standards (IM22-743 and IM22-736). [Figure 7-1] Graphs are presented showing the corneometry (water retention) of IM22-782 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (FIG. 7A) and various lipid standards (IM22-743 and IM22-736) (FIG. 7B). [Figure 7-2] The TEWL of IM22-782 as a function of time in comparison with various standards is presented. [Figure 8] Graphs are presented showing the corneometry (water retention) of IM22-780 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (FIG. 8A) and various lipid standards (IM22-743 and IM22-736) (FIG. 2B). [Figure 9A] A comparative plot is presented showing the magnetization signal from various gels on porcine skin, normalized to correct for the different signal decay processes exhibited. The fitted dotted and dashed lines correspond to the unbound and embedded water regimes. The vertical dashed line represents the calculated value of the expected evaporation completion time point. [Figure 9B] We present an expanded view of Figure 9A , which includes three equations as illustrated by the dashed lines, primarily zooming in on the central embedded water regime shown in Figure 9A . DMPC-LPC consistently exhibits the smallest slope, meaning it has the lowest nominal shrinkage rate, indicating that its embedded water molecules remain for the longest time. [Figure 10A] A comparative plot showing the magnetization signal from various gels on pig skin is presented (absolute values). [Figure 10B]A comparative plot showing the decay of the echo signal along a 120π-pulse after a π / 2 pulse is presented. Each point is the average of 100 such sequence repetitions. [Figure 11] A comparative plot showing the cumulative average mass loss after gel deposition as measured by analytical balance is presented. Blue circles: 5% glycerin, red squares: DMPC, green triangles: DMPC-LPC. DETAILED DESCRIPTION OF THE INVENTION

[0076] In some embodiments thereof, the present invention relates to cosmetics, and more particularly, but not exclusively, to cosmetic compositions and products incorporating therein liposomes formed from lipid bilayer-forming materials and polymeric materials.

[0077] Before describing at least one embodiment of the present invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or illustrated by the examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0078] While investigating liposome-containing solutions, the inventors discovered that incorporating liposomes comprising a lipid-derived polymeric compound, also referred to herein as a "polymeric compound," "lipid-polymer conjugate," or abbreviated as "LPC," and optionally a bilayer-forming lipid, into a topical composition or formulation successfully increases skin hydration and also increases the duration of the moisture-retaining layer on the skin (see the Examples section below). The inventors envisioned the use of such liposomes as advantageous components of cosmetic compositions, formulations, or products, particularly in such compositions, formulations, or products that utilize phospholipids or phospholipid-containing polymeric materials, in addition to or in place of the phospholipids or phospholipid-containing polymeric materials currently commonly included in cosmetic compositions, formulations, or products.

[0079] Consequently, specific embodiments of the present teachings propose cosmetic formulations (e.g., for topical application) that include such lipid-derived polymeric compounds and / or liposomes containing same.

[0080] According to some of the optional embodiments described herein, the polymeric compound is as described in U.S. Provisional Patent Application No. 63 / 402,097, filed August 30, 2022, and / or a concurrently filed PCT international patent application having attorney docket number 97558, which claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 402,097.

[0081] According to an aspect of some embodiments of the present invention, there is provided a cosmetic or cosmeceutical composition comprising a liposome as defined herein in any corresponding embodiment and any combination thereof, and a cosmetically acceptable carrier.

[0082] As used throughout this specification, the term "cosmetic product" with respect to any composition and method disclosed herein (and any other embodiment) refers to a composition that enhances the appearance or odor of the human body.

[0083] In some embodiments, the term "cosmetic" follows the definitions of regulatory agencies around the world. For example, in some embodiments, the term "cosmetic" follows the U.S. Food and Drug Administration (FDA) definition, which states that the term is "intended for application to the human body to cleanse, beautify, promote attractiveness, or alter appearance without affecting the structure or function of the body."

[0084] As used herein, the phrase "cosmeceutical composition" refers to a cosmetically topically administered composition that contains biologically active ingredients, i.e., compounds that exhibit biological activity, such as, for example, anti-inflammatory, antibacterial, and / or antioxidant activity.

[0085] The terms "keratinous material," or "keratinous matrix," or "keratinous tissue" are used interchangeably herein and in some embodiments of the present invention refer to materials, substrates, or tissues in which keratin is concentrated, including, for example, nails, hair, and skin, particularly areas of the body such as the face, cheeks, hands, body, legs, around the eyes, eyelids, and lips.

[0086] "Skin" means the outermost protective covering of mammals, composed of cells such as keratinocytes, fibroblasts, and melanocytes. Skin includes an outer epidermal layer and an underlying dermal layer. Skin may also include hair and nails, as well as other cell types commonly associated with skin, such as muscle cells, Merkel cells, Langerhans cells, macrophages, stem cells, sebocytes, nerve cells, and adipocytes.

[0087] As used herein and in the art, the term "liposome" refers to an artificially prepared vesicle comprising a bilayer composed of amphiphilic lipid molecules. In an aqueous medium, the bilayer is typically configured such that the hydrophilic portion of the amphiphilic lipid is exposed to the medium on both surfaces of the bilayer, while the lipophilic portion of the lipid is located in the inner portion of the bilayer, and therefore less exposed to the medium. Examples of liposomes that can be used in any one of the embodiments described herein include, without limitation, small unilamellar vesicles, large unilamellar vesicles, and multilamellar vesicles.

[0088] As described herein, liposomes according to embodiments include, among other things, polymeric compounds.

[0089] Polymer compound (LPC): According to an aspect of some embodiments of the present invention, there are provided polymeric compounds generally represented by Formula I, as described in more detail herein below. [ka] (In the formula, m is zero or a positive integer; n is an integer of at least 2, at least 5, preferably at least 10 (e.g., from 10 to 200); Y is a backbone unit that forms the polymer backbone of the polymer compound, X is a lipid moiety as described herein in any corresponding embodiment; L is absent or a linking moiety, and Z has the general formula II: [ka] (In the formula, The dashed (wavy) lines represent the points of attachment to the respective Y backbone unit or to the linking moiety L, if present; A is a substituted or unsubstituted hydrocarbon; B is an oxygen atom or is absent, and R1 to R3 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heteroalicyclic, aryl, and heteroaryl.

[0090] Formula I is referred to herein simply as: X-[Y(-LZ)] n [Y] m - which should be considered interchangeable with the schematic diagram above, where X is -[Y(-LZ)] n [Y] m - a lipid moiety conjugated to a polymer moiety.

[0091] Polymer part: As used herein, the term "polymer" refers to a compound having at least two repeat units (and more preferably at least three repeat units), where the repeat units are identical or similar. It should be understood that a compound of general formula I is, by definition, a polymer when n is at least 2, since it contains at least two of the backbone units represented by Y.

[0092] As used herein, the phrase "polymeric moiety" refers to a portion of a polymeric compound having general formula Ia (according to any of the embodiments described herein with respect to general formula I). [ka] wherein m, n, Y, L, and Z are as defined herein for general formula I, and the dashed (wavy) line represents the point of attachment to the X lipid moiety.

[0093] Formula Ia is referred to herein simply as: -[Y(-LZ)] n [Y] m - and this should be considered as being interchangeable with the above schematic diagram.

[0094] As used herein, the phrase "polymeric compound" further encompasses compounds having a "polymer portion" as described herein having at least one unit (e.g., according to Formula Ia, where n is at least 1), provided that the lipid portion (e.g., the lipid portion represented by X) as described herein has a similar unit. For example, if the lipid portion contains a phosphate group (e.g., the lipid portion is a glycerophospholipid portion) and a single unit of the polymer portion has a phosphate group, the two phosphate groups can be considered a repeating unit.

[0095] However, in preferred embodiments, n is at least 2, so that the polymeric portion itself has at least 2 units. In some embodiments, n is at least 3.

[0096] As used herein, the term "backbone unit" refers to a repeating unit, where the linking (e.g., sequential linking) of multiple repeating units forms a polymer backbone. Multiple linked repeating units are themselves also referred to herein as a "polymer backbone." A polymer segment as described herein may include multiple repeating backbone units that are identical to one another, thereby forming a homopolymer segment, or alternatively, may include two or more types of repeating backbone units that are linked to one another randomly or in a certain order (e.g., in two or more blocks or alternating sequences), thereby forming a copolymer segment.

[0097] As shown in Formulas I and Ia, L and Z together form a pendant group of at least a portion of a backbone unit, which group will be referred to herein for brevity simply as the "pendant group."

[0098] Each skeletal unit Y having a pendant group (i.e., a unit represented by Y(-LZ), the number of which is represented by the variable n) and each skeletal unit Y having no pendant group (the number of which is represented by the variable m) are also referred to herein as "monomer units."

[0099] The backbone unit can optionally be a unit of a polymerizable monomer or a polymerizable portion of a monomer. A variety of polymerizable monomers and moieties will be known to those skilled in the art, and the structures of such monomeric units (e.g., monomer units) that result upon polymerization will also be known to those skilled in the art.

[0100] "Unit of polymerizable monomer" refers to a modified form of a polymerizable monomer and / or a portion of a polymerizable monomer that remains after polymerization.

[0101] Some of the polymerizable monomers may be formed, for example, by a condensation reaction in which at least one atom or group in the monomer (e.g., a hydrogen atom or a hydroxyl group), and optionally at least two atoms or groups in the monomer (e.g., a hydrogen atom and a hydroxyl group), are replaced with a covalent bond with another polymerizable monomer.

[0102] Modified forms of polymerizable monomers can be formed, for example, by ring opening (where the covalent bond between two atoms in the ring is broken and each of the two atoms is optionally bonded to another polymerizable monomer) and / or by addition to an unsaturated bond, where the unsaturated bond between two adjacent atoms is broken (e.g., conversion of an unsaturated double bond to a saturated bond or conversion of an unsaturated triple bond to an unsaturated double bond) and the two atoms are optionally each bonded to another polymerizable monomer.

[0103] Modified forms of polymerizable monomers can consist essentially of the same atoms as the original monomer, e.g., differing only in rearrangements of covalent bonds, or can alternatively have a different atomic composition, e.g., polymerization involves a condensation reaction (e.g., as described herein).

[0104] Examples of backbone units include, but are not limited to, substituted or unsubstituted hydrocarbons, such as alkylene units (which may form substituted or unsubstituted hydrocarbon backbones); hydroxycarboxylic acid units, such as glycolate, lactate, hydroxybutyrate, hydroxyvalerate, hydroxycaproate, and hydroxybenzoate units (which may form polyester backbones); dicarboxylic acid units, such as adipate, succinate, terephthalate, and naphthalenedicarboxylic acid units (which may be combined with diols to form polyester backbones and / or with diamines to form polyamides); diol units, such as ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, and bisphenol A units (which may form polyether backbones or may be combined with dicarboxylic acids to form polyester backbones); diamine units, such as alkylenediamines, such as paraphenylenediamine and hexylenediamine (which may be combined with dicarboxylic acids to form polyamide backbones); carbamate units (which may form polyurethane backbones); amino acid residues (which may form polypeptide backbones); and sugar moieties (which may form polysaccharide backbones).

[0105] In some embodiments of any of the embodiments described herein, Y is a substituted or unsubstituted alkylene unit.

[0106] In some embodiments, Y is a substituted or unsubstituted ethylene unit, ie, an alkylene unit two atoms in length.

[0107] The polymer backbone in which Y is a substituted or unsubstituted ethylene unit may optionally be such a polymer backbone formed by polymerizing ethylene (CH=CH) and / or its substituted derivatives (also referred to herein as "vinyl monomers"). Such polymerizations are well-studied procedures, and those skilled in the art will be aware of many techniques for carrying out such polymerizations.

[0108] Any embodiment described herein that refers to a polymer backbone formed by polymerization should be understood to encompass any polymer backbone having a structure that can be formed by such polymerization, regardless of whether the polymer backbone is actually formed by such polymerization (or other type of polymerization).

[0109] As is well known in the art, the unsaturated bonds of ethylene and substituted ethylene derivatives become saturated upon polymerization, and therefore the backbone unit of the polymer backbone formed by polymerization is saturated, but it can also be referred to as a unit of the unsaturated compound it resembles (e.g., a "vinyl monomer" or an "olefin monomer").

[0110] Polymers that can be formed from unsaturated monomers such as vinyl and olefin monomers are also referred to by the terms "polyvinyl" and "polyolefin," respectively.

[0111] As used herein, an "unsubstituted" alkylene unit (e.g., an ethylene unit) refers to an alkylene unit that has no substituents other than the pendant group (represented as (-LZ)) discussed herein. That is, an alkylene unit attached to said pendant group is considered unsubstituted when there are no substituents elsewhere on the alkylene unit.

[0112] In some embodiments of any of the embodiments described herein, Y has the formula -CR4R5-CR6D-.

[0113] When Y is a backbone unit that is not attached to L or Z (i.e., a pendant group as described herein), D is R7 (a terminal group as defined herein), and when Y is a backbone unit that is attached to L or Z, D is a covalent bond or linking group that attaches Y to L or Z. The linking group can optionally be -O-, -S-, arylene, sulfinyl, sulfonyl, phosphate, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, urea, thiourea, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, or amino.

[0114] R4 to R7 are each independently hydrogen, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, cyano, nitro, azido, azo, phosphate, phosphonyl, phosphinyl, oxo, carbonyl, thiocarbonyl, urea, thiourea, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, or amino.

[0115] Throughout this specification, the phrase "linking group" refers to a group (eg, a substituent) that joins two or more moieties in a compound.

[0116] Throughout this specification, the phrase "terminal group" refers to a group (eg, a substituent) that is attached to a single moiety in a compound through one atom of the group.

[0117] When each of R4-R6 is hydrogen and D is a covalent bond or linking group, Y is an unsubstituted ethylene group attached (through D) to a pendant group described herein.

[0118] When each of R4 through R7 is hydrogen (and D is R7), Y is an unsubstituted ethylene group that is not attached to a pendant group as described herein.

[0119] In some embodiments of any of the embodiments described herein, R4 and R5 are each hydrogen. Such embodiments include polymer backbones formed from many commonly used vinyl monomers (including ethylene), including, for example, olefins (e.g., ethylene, propylene, 1-butylene, isobutylene, 4-methyl-1-pentene), vinyl chloride, styrene, vinyl acetate, acrylonitrile, acrylates and their derivatives (e.g., acrylate esters, acrylamides), and methacrylates and their derivatives (e.g., methacrylate esters, methacrylamides).

[0120] In some embodiments of any of the embodiments described herein, R6 is hydrogen. In some such embodiments, R4 and R5 are each hydrogen.

[0121] In some embodiments of any embodiment described herein, R6 is methyl. In some such embodiments, R4 and R5 are each hydrogen. In some such embodiments, the backbone units are methacrylate units or derivatives thereof (e.g., methacrylate esters, methacrylamides).

[0122] In some embodiments of any of the embodiments described herein, the linking group represented by variable D is -O-, -C(=O)O-, -C(=O)NH-, or phenylene. In an exemplary embodiment, D is -C(=O)O-.

[0123] For example, the backbone unit may optionally be a vinyl alcohol derivative (e.g., an ester or ether of a vinyl alcohol unit) when D is -O-, an acrylate or methacrylate derivative (e.g., an ester of an acrylate or methacrylate unit) when D is -C(=O)O-, an acrylamide or methacrylamide unit when D is -C(=O)NH-, and / or a styrene derivative (e.g., a substituted styrene unit) when D is phenylene.

[0124] In some embodiments of any of the embodiments described herein, L is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length. In some embodiments, the hydrocarbon is unsubstituted. In some embodiments, the hydrocarbon is -(CH) i - (wherein i is an integer of 1 to 10).

[0125] In some embodiments of any of the embodiments described herein, L is a substituted or unsubstituted ethylene group. In some embodiments, L is an unsubstituted ethylene group (—CH2CH2—).

[0126] In some embodiments of any embodiment described herein, B is an oxygen atom. In some such embodiments, L is a hydrocarbon according to any corresponding embodiment described herein (i.e., L is absent), and Z is a phosphate group attached to L.

[0127] In some embodiments of any embodiment described herein, B is absent. In some such embodiments, L is a hydrocarbon according to any corresponding embodiment described herein (i.e., L is absent), and Z is a phosphonate group bonded to L. In some embodiments, L is also absent, and thus the phosphorus atom of formula II is bonded directly to Y.

[0128] In some embodiments of any of the embodiments described herein, A is a substituted or unsubstituted hydrocarbon of 1 to 4 carbon atoms in length.

[0129] In some embodiments of any of the embodiments described herein, A is an unsubstituted hydrocarbon. In some such embodiments, the unsubstituted hydrocarbon is 1 to 4 carbon atoms in length. In some embodiments, the hydrocarbon is a straight chain unsubstituted hydrocarbon, i.e., -(CH2) j - (wherein j is an integer of 1 to 4).

[0130] In some embodiments of any of the embodiments described herein, A is a substituted or unsubstituted ethylene group.

[0131] In some embodiments of any of the embodiments described herein, A is an unsubstituted ethylene group (-CHCH-). In such embodiments, the moiety having general formula II (represented by variable Z) is similar to or identical to a phosphoethanolamine or phosphocholine moiety. Phosphoethanolamine and phosphocholine moieties are present in many naturally occurring compounds (e.g., phosphatidylcholines, phosphatidylethanolamines).

[0132] In some embodiments of any of the embodiments described herein, A is an ethylene group substituted with a C-carboxy group. In some embodiments, the C-carboxy is attached to the carbon atom adjacent to the nitrogen atom depicted in Formula II (rather than the carbon atom attached to the oxygen atom depicted). In such embodiments, the moiety having general formula II (represented by variable Z) is similar to or identical to a phosphoserine moiety. Phosphopserine occurs in many naturally occurring compounds (e.g., phosphatidylserines).

[0133] Without being bound to any particular theory, it is believed that moieties similar to or identical to naturally occurring moieties such as phosphocholine, phosphoethanolamine and / or phosphoserine may be particularly biocompatible.

[0134] In some embodiments of any of the embodiments described herein, R1-R3 (the substituents of the nitrogen atom depicted in general formula II) are each independently hydrogen or C 1~4 -alkyl. In some embodiments, R1-R3 are each independently hydrogen or methyl. In some embodiments, R1-R3 are each methyl. In some such embodiments, R1-R3 are each hydrogen.

[0135] The variable n can be considered to represent the number of backbone units (represented by variable Y) that are substituted with pendant groups represented by (-LZ), and the variable m can be considered to represent the number of backbone units that are not substituted with such pendant groups. The sum n+m can be considered to represent the total number of backbone units in the polymer backbone. The ratio n / (n+m) can be considered to represent the percentage of backbone units that are substituted with pendant groups represented by (-LZ).

[0136] In some embodiments of any of the embodiments described herein, the percentage of skeletal units (represented by the variable Y) substituted with pendant groups represented by (-LZ) (represented by the formula: 100%*n / (n+m)) is at least 20%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 30%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 40%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 50%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 60%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 70%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 80%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 90%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 95%. In some embodiments, the percentage of skeletal units substituted with said pendant groups is at least 98%.

[0137] In some embodiments of any of the embodiments described herein, m is 0, and therefore each of the backbone units (represented by the variable Y) is substituted with a pendant group represented by (-LZ).

[0138] In some embodiments of any of the embodiments described herein, n is at least 5. In some embodiments, n is at least 10. In some embodiments, n is at least 15.

[0139] In some embodiments of any of the embodiments described herein, n is in the range of 2 to 1,000, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 2 to 500, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 2 to 200, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 2 to 100, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 2 to 50, including any intermediate values ​​and subranges therebetween. In some such embodiments, m is 0.

[0140] In some embodiments of any of the embodiments described herein, n is in the range of 3 to 1,000, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 3 to 500, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 3 to 200, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 3 to 100, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 3 to 50, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 5 to 50, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 10 to 50, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 10 to 25, including any intermediate values ​​and subranges therebetween, and in some such embodiments, m is 0.

[0141] In some embodiments of any of the embodiments described herein, n is in the range of 10 to 200, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 10 to 180, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 10 to 150, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 10 to 120, including any intermediate values ​​and subranges therebetween. In some such embodiments, m is 0.

[0142] In some embodiments of any of the embodiments described herein, n is at least 30.

[0143] In some embodiments of any of the embodiments described herein, n is in the range of 30 to 200, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 30 to 180, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 30 to 150, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 30 to 120, including any intermediate values ​​and subranges therebetween. In some such embodiments, m is 0.

[0144] In some embodiments of any of the embodiments described herein, n is in the range of 30 to 70, including any intermediate values ​​and subranges therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 35 to 65, including any intermediate values ​​and subranges therebetween. In some such embodiments, m is 0.

[0145] In some embodiments of any of the embodiments described herein, n is at least 50, or at least 60, or at least 80.

[0146] In some embodiments of any of the embodiments described herein, n is in the range of 50 to 200, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 50 to 180, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 50 to 150, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 50 to 120, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 80 to 120, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 50 to 100, including any intermediate value and subrange therebetween. In some embodiments of any of the embodiments described herein, n is in the range of 50 to 80, including any intermediate value and subrange therebetween. In some such embodiments, m is 0.

[0147] In some embodiments of any embodiment described herein, when n is less than 80, or less than 70, or less than 50, or less than 30, or in the ranges of 10-50, or 30-60, or 30-80, or 30-70, or 50-80, as described herein in any corresponding embodiment, the polymeric compound is referred to herein as "short chain" or "S."

[0148] In some embodiments of any embodiment described herein, when n is greater than 80, or greater than 100, or in the range of 50-150, or 50-120, or 80-150, or 80-120, as described herein in any corresponding embodiment, the polymeric compound is referred to herein as "long chain" or "L."

[0149] In some embodiments of any of the embodiments described herein, n is in the range of 10 to 50, including any intermediate values ​​and subranges therebetween, and in some such embodiments, m is 0.

[0150] In some embodiments of any of the embodiments described herein, n is in the range of 50 to 80, including any intermediate values ​​and subranges therebetween, and in some such embodiments, m is 0.

[0151] In some embodiments of any of the embodiments described herein, n is in the range of 80 to 120, including any intermediate values ​​and subranges therebetween, and in some such embodiments, m is 0.

[0152] In some embodiments of any of the embodiments described herein, m is in the range of 0 to 1,000, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 2 to 1,000 (including any intermediate value and subrange therebetween), and therefore the total number of backbone units is in the range of 2 to 2,000, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 3 to 1,000, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 500, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 200, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 100, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 5 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 10 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 50 to 80, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 80 to 120, including any intermediate value and subrange therebetween.

[0153] In some embodiments of any of the embodiments described herein, m is in the range of 0 to 500, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 2 to 1,000, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 3 to 1,000, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 500, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 200, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 100, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 5 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 10 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 50 to 80, including any intermediate value and subrange therebetween, hi some embodiments, n is in the range of 80 to 120, including any intermediate value and subrange therebetween.

[0154] In some embodiments of any of the embodiments described herein, m is in the range of 0 to 200, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 2 to 1,000, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 3 to 1,000, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 500, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 200, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 100, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 5 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 10 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 50 to 80, including any intermediate value and subrange therebetween, hi some embodiments, n is in the range of 80 to 120, including any intermediate value and subrange therebetween.

[0155] In some embodiments of any of the embodiments described herein, m is in the range of 0 to 100, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 2 to 1,000, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 3 to 1,000, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 500. In some embodiments, n is in the range of 3 to 200, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 100, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 50. In some embodiments, n is in the range of 5 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 10 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 50 to 80, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 80 to 120, including any intermediate value and subrange therebetween.

[0156] In some embodiments of any of the embodiments described herein, m is in the range of 0 to 50, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 2 to 1,000, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 3 to 1,000, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 500, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 200, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 100, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 5 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 10 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 50 to 80, including any intermediate value and subrange therebetween, hi some embodiments, n is in the range of 80 to 120, including any intermediate value and subrange therebetween.

[0157] In some embodiments of any of the embodiments described herein, m is in the range of 0 to 20, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 2 to 1,000, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 3 to 1,000, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 500, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 200, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 100, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 5 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 10 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 50 to 80, including any intermediate value and subrange therebetween, hi some embodiments, n is in the range of 80 to 120, including any intermediate value and subrange therebetween.

[0158] In some embodiments of any of the embodiments described herein, m is in the range of 0 to 10, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 2 to 1,000, including any intermediate value and subrange therebetween. In some such embodiments, n is in the range of 3 to 1,000, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 500, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 200, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 100, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 3 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 5 to 50, including any intermediate value and subrange therebetween. In some embodiments, n is in the range of 10 to 50, including any intermediate value and subrange therebetween. In some of any of the embodiments described herein for m, n is in the range of 30 to 70, as described herein in any corresponding embodiment, or represents a short chain polymer moiety as described herein. In some such embodiments, n is in the range of 50 to 80, including any intermediate values ​​and subranges therebetween.

[0159] In some of any of the embodiments described herein for m, n is in the range of 80 to 120, as described herein in any corresponding embodiment, or represents a long chain polymer moiety, as described herein.

[0160] In some embodiments of any of the embodiments described herein, the backbone units Y substituted with pendant groups represented by (-LZ) are the same as the backbone units Y that are not substituted with pendant groups (e.g., when m is at least 1). In alternative embodiments, at least a portion of the backbone units Y substituted with pendant groups are different from a portion of the backbone units Y that are not substituted with pendant groups (e.g., when m is at least 1).

[0161] In some embodiments of any of the embodiments described herein, the plurality of backbone units Y (as indicated by variable n) substituted with pendant groups represented by (-LZ) are the same as one another. In alternative embodiments, at least a portion of the plurality of backbone units Y substituted with pendant groups represented by (-LZ) is different from a second portion of the plurality of backbone units Y substituted with pendant groups.

[0162] In some embodiments of any of the embodiments described herein, the pendant groups (-LZ) attached to the backbone units Y are the same as one another (as indicated by the variable n). In alternative embodiments, at least some of the pendant groups (-LZ) attached to the backbone units Y are different from one another (e.g., differing in the identity of any one or more of A, B, R1, R2, R3, and L).

[0163] In any embodiment described herein where two or more backbone units Y are not substituted with pendant groups described herein (i.e., when m is greater than 1), the plurality of backbone units Y (as indicated by variable m) that are not substituted with pendant groups are identical to one another. In alternative embodiments where m is greater than 1, at least some of the backbone units Y that are not substituted with pendant groups described herein are different from at least a second portion of the plurality of backbone units Y that are not substituted with pendant groups.

[0164] The number of types of backbone units substituted with pendant groups, the number of types of backbone units not substituted with pendant groups (if any such units are present), and / or the number of types of pendant groups in the polymer moiety can each independently be any number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more).

[0165] In some embodiments of any embodiment described herein, the polymeric segment is a copolymer segment, i.e., the polymeric segment comprises at least two different types of monomeric units. In some such embodiments, the different types of monomeric units differ in whether they comprise a pendant group (-LZ) according to any corresponding embodiment described herein (e.g., when m is at least 1), and / or the different types of monomeric units differ in the type of backbone unit Y, and / or the different types of monomeric units differ in the type of pendant group (-LZ).

[0166] For example, in some embodiments of any of the embodiments described herein, the backbone units Y in each of the Y(-LZ) units can optionally be the same or different, while the L and Z moieties are the same between the Y(-LZ) units. In some such embodiments, the backbone units not substituted with pendant groups (if any such units are present) can optionally be the same as the backbone units Y in each of the Y(-LZ) units. Alternatively, the backbone units not substituted with pendant groups (if any such units are present) can optionally be different from the backbone units Y in each of the Y(-LZ) units (while optionally being the same between all of the backbone units not substituted with pendant groups).

[0167] In some embodiments of any of the embodiments described herein, the L moieties in each of the Y(-LZ) units can optionally be the same or different, while the backbone units Y and Z moieties are the same among the Y(-LZ) units. In some such embodiments, the backbone units not substituted with pendant groups (if any such units are present) can optionally be the same as the backbone units Y in each of the Y(-LZ) units. Alternatively, the backbone units not substituted with pendant groups (if any such units are present) can optionally be different from the backbone units Y in each of the Y(-LZ) units (while optionally being the same among all of the backbone units not substituted with pendant groups).

[0168] In some embodiments of any of the embodiments described herein, the Z moieties in each of the Y(-LZ) units can optionally be the same or different, while the backbone units Y and Z moieties are the same among the Y(-LZ) units. In some such embodiments, the backbone units not substituted with pendant groups (if any such units are present) can optionally be the same as the backbone units Y in each of the Y(-LZ) units. Alternatively, the backbone units not substituted with pendant groups (if any such units are present) can optionally be different from the backbone units Y in each of the Y(-LZ) units (while optionally being the same among all of the backbone units not substituted with pendant groups).

[0169] In any embodiment described herein in which the polymeric portion is a copolymeric portion, any two or more different types of monomeric units can be randomly or non-randomly distributed throughout the polymeric portion. When the different types of monomeric units are non-randomly distributed, the copolymer can be any one characterized by a non-random distribution, such as an alternating copolymer, a periodic copolymer, and / or a block copolymer.

[0170] In some of the embodiments described herein, the polymer moiety that is attached at one of its ends to a lipid moiety X may have a different terminal group at the other end (i.e., at the end closer to the backbone unit Y that does not have a pendant group if m is at least 1, or at the other end closer to the backbone unit Y that includes a pendant group if m is 0).

[0171] The end groups may be inherent end groups from the monomers used to form the polymeric compound and / or from the method used to polymerize the monomers, or may otherwise be conjugated to or generated within the terminus of the polymeric moiety. For example, the end groups may be hydrogen, halo, alkyl, hydroxy, carboxy, etc., or may be targeted moieties as described in more detail below. In some of the embodiments described herein, the end groups are hydrogen or halo. In some of the embodiments described herein, the end groups are derived from the initiators used to form the polymeric compound as described in any corresponding embodiment herein and exemplified in the Examples section below; in some of these embodiments, the end groups are halo (e.g., chloro or bromo).

[0172] In some of any of the embodiments described herein, the terminal group is a functional group suitable for electron transfer radical polymerization, such as variable Ri in Formula V as described herein in any corresponding embodiment.

[0173] In some embodiments of any of the embodiments described herein, when n is less than 60, or less than 50, or less than 30, as described herein in any corresponding embodiment, the polymeric compound is referred to herein as "short chain" or "S."

[0174] In some embodiments of any of the embodiments described herein, when n is less than 80, greater than 50, or greater than 60, as described herein in any corresponding embodiment, the polymeric compound is referred to herein as "medium chain."

[0175] In some embodiments of any of the embodiments described herein, when n is greater than 80, or greater than 90, or greater than 100, the polymeric compound is referred to herein as "long chain" or "L," as described herein in any corresponding embodiment.

[0176] In some embodiments of any of the embodiments described herein, n is in the range of 50 to 120, including any intermediate values ​​and subranges therebetween, and in some such embodiments, m is 0.

[0177] In some embodiments of any of the embodiments described herein, n is in the range of 60 to 120, including any intermediate values ​​and subranges therebetween, and in some such embodiments, m is 0.

[0178] In some embodiments of any of the embodiments described herein, n is in the range of 80 to 120, or 90 to 120, or 100 to 120, or 100 to 110, including any intermediate values ​​and subranges therebetween. In some such embodiments, m is 0.

[0179] In some of any of the embodiments described herein for m, n is in the range of 80 to 120, as described herein in any corresponding embodiment, or represents a long chain polymer moiety, as described herein.

[0180] Lipid part: A lipid moiety according to any embodiment of this section (represented by variable X in Formula I herein) may be attached to a polymer moiety according to any of the embodiments described herein in this section with respect to polymer moieties.

[0181] The lipid moiety can be optionally derived from any lipid known in the art, including, but not limited to, naturally occurring lipids. The derivation of the lipid moiety from a lipid can optionally involve replacing a hydrogen atom at any position of the lipid with [Y(-LZ)] in general formula I. n [Y] m(i.e., a polymer moiety represented by general formula Ia).

[0182] In some embodiments of any of the embodiments described herein, the lipid moiety (according to any corresponding embodiment described herein) is attached to a Y(-LZ) unit (according to any of the embodiments described herein for Y, L and / or Z), i.e., a backbone unit substituted with a pendant group as described herein (e.g., rather than a backbone unit that is not substituted with a pendant group).

[0183] Alternatively or additionally, in some embodiments of any embodiment described herein, where m is at least 1, the lipid moiety (according to any corresponding embodiment described herein) may optionally be attached to a backbone unit (Y) that is not substituted with a pendant group as described herein (e.g., rather than being attached to a backbone unit substituted with a pendant group). For example, the polymer portion may optionally be a copolymer in which the identity of the backbone unit attached to the lipid moiety varies randomly between molecules. Thus, the depiction in Formula I that X is attached to a backbone unit substituted with a pendant group (i.e., Y-(LZ)) rather than to an unsubstituted backbone unit Y is arbitrary and not intended to be limiting.

[0184] In some embodiments of any of the embodiments described herein, the lipid moiety is a portion of a lipid that is a fatty acid, a monoglyceride, a diglyceride, a triglyceride, a glycerophospholipid, a sphingolipid, or a sterol, hi some embodiments, the lipid is a glycerophospholipid.

[0185] In some embodiments of any of the embodiments described herein, the lipid moiety comprises at least one fatty acid moiety (e.g., an acyl group derived from a fatty acid). The fatty acid moiety can be derived from a saturated or unsaturated fatty acid. For example, the lipid moiety can consist of a fatty acid moiety, or can be a monoglyceride moiety containing one fatty acid moiety, a diglyceride moiety containing two fatty acid moieties, or a triglyceride moiety containing three fatty acid moieties.

[0186] Examples of fatty acid moieties that may optionally be included in the lipid moiety include, but are not limited to, lauroyl, myristoyl, palmitoyl, stearoyl, palmitoleoyl, oleoyl, and linoleoyl.

[0187] Suitable examples of glycerophospholipids include, without limitation, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol.

[0188] In some embodiments of any of the embodiments described herein, the lipid moiety represented by variable X has the general formula I and is represented by formula IV: [ka] (In the formula, The dashed (wavy) lines represent points of attachment to the polymer backbone (i.e., via the respective Y backbone units); F1, F2, F3, and F4 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, acyl, alkoxy, thioalkoxy, carboxy, and thiocarboxy, and at least one of F1, F2, F3, and F4 is not hydrogen and is at least 10 carbon atoms in length; J is -OP(=O)(OH)-O- or absent; K is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length or is absent; M is a linking group selected from the group consisting of -O-, -S-, amino, sulfinyl, sulfonyl, phosphate, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, urea, thiourea, carbamyl, thiocarbamyl, amido, carboxy, and sulfonamido, or is absent; and Q is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length or is absent; When M does not exist, Q does not exist either.)

[0189] Q is attached to a backbone unit of the polymer backbone according to any corresponding embodiment described herein, or alternatively, when Q is absent, M is attached to said backbone unit.

[0190] When M is absent, Q is also absent and K is attached to a backbone unit of the polymer backbone according to any corresponding embodiment described herein.

[0191] In some embodiments of any of the embodiments described herein for Formula IV, when J is absent, M is absent.

[0192] In some embodiments of any of the embodiments described herein for Formula IV, when J is -OP(=O)(OH)-O-, M is other than an amide, and / or Q includes an aryl moiety.

[0193] In some embodiments of any of the embodiments described herein for Formula IV, at least one of F1, F2, F3, and F4 is preferably an alkoxy, thioalkoxy, acyl, or carboxy group at least 10 carbon atoms in length, e.g., from 8 to 40, or from 10 to 40, or from 10 to 30 carbon atoms in length.

[0194] In some such embodiments, the alkoxy, thioalkoxy, acyl, and / or carboxy have alkyl moieties derived from fatty acyl as described herein, such as lauroyl, myristoyl, palmitoyl, stearoyl, palmitoleoyl, oleoyl, and linoleoyl.

[0195] In some embodiments of any of the embodiments described herein for Formula IV, at least one or at least two of F1, F2, F3, and F4 are each independently a thioalkoxy. In some of these embodiments, the thioalkoxy is at least 10 carbon atoms in length, e.g., 8 to 40, or 10 to 40, or 10 to 30 carbon atoms in length. In an exemplary embodiment, the alkyl is 15 carbon atoms in length and is derived from palmitic acid. In some of these embodiments, the thioalkoxy has an alkyl group that is that of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid. In some of these embodiments, each of F1 and F2 is each independently a thioalkoxy as described herein and can be the same or different, preferably the same. In some of these embodiments, F3 and F4 are each hydrogen.

[0196] In some embodiments of any of the embodiments described herein, at least one or at least two of F1, F2, F3, and F4 are each independently carboxy. In some of these embodiments, carboxy is at least 10 carbon atoms in length, e.g., 8 to 40, or 10 to 40, or 10 to 30 carbon atoms in length. In an exemplary embodiment, carboxy is 16 carbon atoms in length and is derived from palmitic acid. In some of these embodiments, carboxy has an alkyl group that is that of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid. In some of these embodiments, at least one or both of F1 and F2 are carboxy as described herein in any corresponding embodiment. In some of these embodiments, both F1 and F2 are carboxy as described herein in any corresponding embodiment, and they can be the same or different, preferably the same. In some of these embodiments, at least one of F3 and F4 is alkyl, which can be the same or different. In some such embodiments, alkyl is a short-chain alkyl of 1 to 6 or 1 to 4 carbon atoms in length, e.g., methyl. Alternatively, each of F3 and F4 is hydrogen.

[0197] According to some of the embodiments described herein, M is other than an amide.

[0198] According to some of the embodiments described herein, M is carboxy.

[0199] According to some of the embodiments described herein, M is carboxy, and at least one or at least two of F1, F2, F3, and F4 are each independently a thioalkoxy. In some of these embodiments, the thioalkoxy is at least 10 carbon atoms in length, e.g., 8 to 40, or 10 to 40, or 10 to 30 carbon atoms in length. In an exemplary embodiment, the alkyl is 15 carbon atoms in length and is derived from palmitic acid. In some of these embodiments, the thioalkoxy has an alkyl group that is that of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid. In some of these embodiments, each of F1 and F2 is each independently a thioalkoxy as described herein and can be the same or different, preferably the same. In some of these embodiments, F3 and F4 are each hydrogen.

[0200] According to some of the embodiments described herein, M is carboxy, and at least one or at least two of F1, F2, F3, and F4 are each independently carboxy. In some of these embodiments, carboxy is at least 10 carbon atoms in length, e.g., 8 to 40, or 10 to 40, or 10 to 30 carbon atoms in length. In an exemplary embodiment, carboxy is 16 carbon atoms in length and is derived from palmitic acid. In some of these embodiments, carboxy has an alkyl group that is that of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid. In some of these embodiments, at least one or both of F1 and F2 are carboxy, as described herein in any corresponding embodiment. In some of these embodiments, both F1 and F2 are carboxy, as described herein in any corresponding embodiment, and they can be the same or different, preferably the same. In some of these embodiments, at least one of F3 and F4 is alkyl, which can be the same or different. In some such embodiments, the alkyl is a short chain alkyl of 1 to 6 or 1 to 4 carbon atoms in length, such as methyl. Alternatively, each of F3 and F4 is hydrogen.

[0201] According to some of the optional embodiments described herein, J is absent.

[0202] According to some of the embodiments described herein, J is absent and M is other than an amide.

[0203] According to some of the embodiments described herein, J is absent and M is carboxy.

[0204] According to some of the embodiments described herein, J is absent and at least one or at least two of F1, F2, F3, and F4 are each independently a thioalkoxy. In some of these embodiments, the thioalkoxy is at least 10 carbon atoms in length, e.g., 8 to 40, or 10 to 40, or 10 to 30 carbon atoms in length. In an exemplary embodiment, the alkyl is 15 carbon atoms in length and is derived from palmitic acid. In some of these embodiments, the thioalkoxy has an alkyl group that is that of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid. In some of these embodiments, each of F1 and F2 is each independently a thioalkoxy as described herein and can be the same or different, preferably the same. In some of these embodiments, F3 and F4 are each hydrogen.

[0205] According to some of the embodiments described herein, J is absent, M is carboxy, and at least one or at least two of F1, F2, F3, and F4 are each independently a thioalkoxy. In some of these embodiments, the thioalkoxy is at least 10 carbon atoms in length, e.g., 8 to 40, or 10 to 40, or 10 to 30 carbon atoms in length. In an exemplary embodiment, the alkyl is 15 carbon atoms in length and is derived from palmitic acid. In some of these embodiments, the thioalkoxy has an alkyl group that is that of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid. In some of these embodiments, each of F1 and F2 is each independently a thioalkoxy as described herein and can be the same or different, preferably the same. In some of these embodiments, F3 and F4 are each hydrogen.

[0206] According to some of the embodiments described herein, J is absent and at least one or at least two of F1, F2, F3, and F4 are each independently carboxy. In some of these embodiments, carboxy is at least 10 carbon atoms in length, e.g., 8 to 40, or 10 to 40, or 10 to 30 carbon atoms in length. In an exemplary embodiment, carboxy is 16 carbon atoms in length and is derived from palmitic acid. In some of these embodiments, carboxy has an alkyl group that is that of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid. In some of these embodiments, at least one or both of F1 and F2 are carboxy as described herein in any corresponding embodiment. In some of these embodiments, both F1 and F2 are carboxy as described herein in any corresponding embodiment, and they may be the same or different, preferably the same. In some of these embodiments, at least one of F3 and F4 is alkyl, which may be the same or different. In some such embodiments, the alkyl is a short chain alkyl of 1 to 6 or 1 to 4 carbon atoms in length, such as methyl. Alternatively, each of F3 and F4 is hydrogen.

[0207] According to some of the embodiments described herein, J is absent, M is carboxy, and at least one or at least two of F1, F2, F3, and F4 are each independently carboxy. In some of these embodiments, carboxy is at least 10 carbon atoms in length, e.g., 8 to 40, or 10 to 40, or 10 to 30 carbon atoms in length. In an exemplary embodiment, carboxy is 16 carbon atoms in length and is derived from palmitic acid. In some of these embodiments, carboxy has an alkyl group that is that of lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, or linoleic acid. In some of these embodiments, at least one or both of F1 and F2 are carboxy as described herein in any corresponding embodiment. In some of these embodiments, both F1 and F2 are carboxy as described herein in any corresponding embodiment, and they may be the same or different, preferably the same. In some of these embodiments, at least one of F3 and F4 is alkyl, which may be the same or different. In some such embodiments, the alkyl is a short chain alkyl of 1 to 6 or 1 to 4 carbon atoms in length, such as methyl. Alternatively, each of F3 and F4 is hydrogen.

[0208] According to some of the embodiments described herein for Formula IV, when J is absent, Q is -C(CH3)2-.

[0209] According to some of the embodiments described herein for Formula IV, when J is absent, M is carboxy and Q is -C(CH3)2-.

[0210] As used herein, the hydrocarbon length represented by the variable K refers to the number of atoms separating J and M (i.e., along the shortest path between J and M) as depicted in Formula IV when J is not present, or the number of atoms separating M and the lipid backbone formed by F1, F2, F3, and F4.

[0211] When K is a substituted hydrocarbon, M may be attached to a carbon atom of the hydrocarbon itself or to a substituent on the hydrocarbon.

[0212] In some embodiments, K is an all-carbon hydrocarbon.

[0213] In some embodiments, K is an unsubstituted hydrocarbon.

[0214] In some embodiments, K is an unsubstituted all-carbon hydrocarbon.

[0215] In some of these optional embodiments, K is an alkyl (alkylene chain or linking group), preferably an unsubstituted, short chain alkyl or alkylene, optionally 1 to 6, or 1 to 4, or 1 to 2 carbon atoms in length.

[0216] According to some of the optional embodiments described herein, K is absent.

[0217] According to some of any of the embodiments described herein, J is absent and K is absent, as described herein in any corresponding embodiment. In some of these embodiments, M is carboxy.

[0218] According to some of the embodiments described herein, Q is a hydrocarbon substituted with at least one aryl (eg, phenyl).

[0219] In some of these embodiments, Q is a hydrocarbon that is an all-carbon hydrocarbon, and in some of these embodiments, the hydrocarbon is an alkyl (alkylene linking group) substituted with at least one aryl (e.g., phenyl), preferably a short chain alkyl (or alkylene) of 1 to 6 or 1 to 4, preferably 1 or 2 carbon atoms in length.

[0220] According to some of the embodiments described herein, Q is methylene substituted with at least one aryl (eg, phenyl).

[0221] According to some of the embodiments described herein, J is -P(=O)(OH)-O-, M is an amide, and Q is a hydrocarbon substituted with at least one aryl (e.g., phenyl), as described herein for any corresponding embodiment and any combination thereof.

[0222] According to some of the embodiments described herein, J is -P(=O)(OH)-O-, M is amide, and Q is methylene substituted with at least one aryl (e.g., phenyl).

[0223] In some embodiments of any of the embodiments described herein for Formula I, the lipid moiety represented by variable X has the general formula III. [ka] (In the formula, The dashed lines (wavy lines) represent the points of attachment to each Y backbone unit, W1 and W2 are each independently hydrogen, alkyl, alkenyl, alkynyl, or acyl, and at least one of W1 and W2 is not hydrogen; J is -P(=O)(OH)-O- or J is absent (thus K is attached directly to the oxygen atom of the depicted glycerol moiety); K is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length; M is a linking group that is -O-, -S-, amino, sulfinyl, sulfonyl, phosphate, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, urea, thiourea, carbamyl, thiocarbamyl, amido, carboxy, or sulfonamido, or M is absent (thus, K is directly bonded to Q); and Q is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length, or Q is absent.

[0224] Q is attached to a backbone unit of the polymer backbone according to any corresponding embodiment described herein, or alternatively, when Q is absent, M is attached to said backbone unit.

[0225] When M is absent, Q is also absent and K is attached to a backbone unit of the polymer backbone according to any corresponding embodiment described herein.

[0226] In some embodiments of any of the embodiments described herein for Formula III, one of W1 and W2 is hydrogen and the other is not hydrogen.

[0227] In some embodiments of any of the embodiments described herein for Formula III, neither W1 nor W2 is hydrogen.

[0228] In some embodiments of any of the embodiments described herein for Formula III, at least one of W1 and W2 is alkyl, alkenyl, alkynyl, or acyl that is 10 to 30 carbon atoms in length. In some embodiments, W1 and W2 are each 10 to 30 carbon atoms in length.

[0229] Examples of acyl groups which may optionally function independently as W1 and / or W2 include, but are not limited to, lauroyl, myristoyl, palmitoyl, stearoyl, palmitoleoyl, oleoyl, and linoleoyl.

[0230] In some embodiments of any of the embodiments described herein for Formula III, J is -P(=O)(OH)-O- (e.g., the lipid moiety is a glycerophospholipid).

[0231] As used herein, the length of a hydrocarbon, represented by the variable K, refers to the number of atoms separating J and M (i.e., along the shortest path between J and M), as shown in Formula III.

[0232] When K is a substituted hydrocarbon, M may be attached to a carbon atom of the hydrocarbon itself or to a substituent of the hydrocarbon.

[0233] In some embodiments of any of the embodiments described herein for Formula III, K is an acyl moiety (e.g., -C(=O)-C(CH3)2-). In some such embodiments, J is absent, and thus K is directly attached to the oxygen atom of the depicted glycerol moiety. In some such embodiments, K comprises a carbonyl linking group (-C(=O)-) attached to the oxygen atom of the glycerol moiety via an ester bond.

[0234] In some embodiments of any of the embodiments described herein for Formula III, K is an ethanolamine moiety (e.g., -CH-CH-NH- or -CH-CH- attached to the nitrogen atom), a serine moiety (e.g., -CH-CH(COH)-NH- or -CH-CH(COH)- attached to the nitrogen atom), a glycerol moiety (e.g., -CH(OH)-CH(OH)-CH-O-), and an inositol moiety (e.g., -cyclohexyl(OH)-O-). In some embodiments, J is -P(=O)(OH)-O-.

[0235] In some embodiments of any of the embodiments described herein for Formula III, M is an amide, optionally -C(=O)NH-.

[0236] In some embodiments, the nitrogen atom of the amide is bound to K. In some such embodiments, K is an ethanolamine or serine moiety described herein.

[0237] In some embodiments of any of the embodiments described herein for Formula III, Q is a substituted alkylene (e.g., 1 to 6, or 1 to 4, or 1 to 2 carbon atoms in length, e.g., a methylene group). In some such embodiments, M is amido or carboxy. In some embodiments, the C(=O) of the amido or carboxy is bonded to Q.

[0238] In some embodiments of any of the embodiments described herein for Formula III, Q is an alkylene group, as described herein, where the methylene group is substituted with one or two substituents, at least one of which is or includes aryl (e.g., phenyl). In some such embodiments, M is an amide. In some embodiments, the C(=O) of the amide is bonded to Q. Alternatively, M is carboxy, where the C(=O) of the carboxy is bonded to Q.

[0239] In some embodiments of any of the embodiments described herein for Formula III, Q is a methylene group substituted with two substituents, at least one of which is or includes an aryl (e.g., phenyl), and the other of which can be, for example, an aryl (e.g., phenyl) or an alkyl (e.g., 1 to 6 or 1 to 4 carbon atoms in length). In some embodiments, the methylene group is substituted with an alkyl group (e.g., C 1~4 -alkyl) and aryl (e.g., phenyl). In some such embodiments, M is amide. In some such embodiments, M is carboxy.

[0240] In some embodiments of any of the embodiments described herein for Formula III, Q is a substituted alkylene (e.g., 1 to 6, or 1 to 4, or 1 to 2 carbon atoms in length, e.g., a methylene group). In some such embodiments, M is amido or carboxy. In some embodiments, the C(=O) of the amido or carboxy is bonded to Q.

[0241] In some embodiments of any of the embodiments described herein for Formula III, Q is an alkylene group as described herein, wherein the methylene group is substituted with one or two substituents. In some embodiments, the methylene group is substituted with one or two alkyl groups (e.g., C 1~4 -alkyl). In some such embodiments, M is other than amido. In some such embodiments, M is carboxy.

[0242] In some embodiments of any of the embodiments described herein for Formula III, Q is a methylene group substituted by two substituents. In some embodiments, the methylene group is substituted with two alkyl groups (e.g., C 1~4 In some such embodiments, M is other than amide. In some such embodiments, M is carboxy.

[0243] According to some of the embodiments described herein for Formula III, when M is an amide, Q is an alkylene substituted with at least one aryl as described herein in any corresponding embodiment.

[0244] According to some of the embodiments described herein, M is other than amide, and Q is as described herein in any corresponding embodiment.

[0245] In some embodiments of any embodiment described herein for Formula III, M and Q are each absent, and K is a terminally substituted or unsubstituted methylene group, such as a methylene group substituted by two substituents (e.g., dimethylmethylene (-C(CH)-), according to any corresponding embodiment described herein related to Q. In some embodiments, K further comprises a carbonyl group, according to any corresponding embodiment described herein.

[0246] In some embodiments of any of the embodiments described herein, J, M, and Q are each absent. In some such embodiments, K comprises a carbonyl linking group (-C(=O)-) bonded directly (via an ester bond) to an oxygen atom of the depicted glycerol moiety and further comprises a substituted or unsubstituted methylene group (e.g., dimethylmethylene). In some embodiments, K consists of a carbonyl linking group and a substituted or unsubstituted methylene group bonded directly (via an ester bond) to an oxygen atom of the depicted glycerol moiety, e.g., K is -C(=O)-C(CH3)2-.

[0247] According to some of the embodiments described herein for Formula IV, F1 is as described herein for OW1. According to some of these embodiments, F3 and F4 are each hydrogen. According to some of these embodiments, J is absent. According to some of these embodiments, M is other than amide.

[0248] According to some of the embodiments described herein for Formula IV, F2 is as described herein for OW2. According to some of these embodiments, F3 and F4 are each hydrogen. According to some of these embodiments, J is absent. According to some of these embodiments, M is other than an amide.

[0249] According to some of the embodiments described herein for Formula IV, F1 is as described herein for OW1 and F2 is as described herein for OW2. According to some of these embodiments, F3 and F4 are each hydrogen. According to some of these embodiments, J is absent. According to some of these embodiments, M is other than an amide.

[0250] According to some of any of the embodiments described herein, the lipid moiety does not include a moiety of formula III, as described herein.

[0251] According to some of the embodiments described herein, the lipid moiety has a moiety of formula III, as described herein, except that M is other than amide (e.g., M is carboxy), and / or Q includes an aryl substituent, as described herein.

[0252] According to some of the optional embodiments described herein for Formula IV, polymeric compounds in which the lipid moiety X is as described in WO 2017 / 109784 are excluded from the scope of the present embodiments.

[0253] Target part: As noted above, in some embodiments of any of the embodiments described herein, at least a portion of the monomer units include a targeting moiety (according to any of the embodiments described herein with respect to the targeting moiety).

[0254] As used herein, a "targeting moiety" refers to a moiety that has the ability to bring a compound (e.g., a compound according to some embodiments of the present invention) into proximity with a selected substance and / or material (which is referred to herein as a "target"). The target is optionally a cell (e.g., a proliferating cell associated with a proliferative disease or disorder), and the proximity is such that the targeting moiety facilitates the compound binding to and / or internalizing the target cell so that the compound can exert its therapeutic effect.

[0255] In any embodiment described herein where m is at least 1, at least a portion of the monomeric units (the number of which is represented by the variable m) comprising a target moiety according to any corresponding embodiment described herein are monomeric units that do not include a pendant group represented by (-LZ). In some such embodiments, each of the monomeric units (according to any corresponding embodiment described herein) that comprise a target moiety is a monomeric unit that includes a pendant group represented by (-LZ) (i.e., a backbone unit Y substituted by (-LZ)), i.e., none of the monomeric units that include a pendant group represented by (-LZ) include said target moiety.

[0256] In any embodiment described herein where m is at least 1, each of the monomeric units (the number of which is represented by variable m) that do not contain a pendant group represented by (-LZ) comprises a target moiety (according to any corresponding embodiment described herein). In some such embodiments, each of the monomeric units that contain a target moiety (according to any corresponding embodiment described herein) is a monomeric unit that does not contain a pendant group represented by (-LZ), i.e., none of the monomeric units that contain a pendant group represented by (-LZ) contain said target moiety, and each of the monomeric units that do not contain a pendant group represented by (-LZ) contain said target moiety.

[0257] In any embodiment described herein where m is at least 1, the monomeric unit comprising a targeting moiety may consist essentially of a backbone unit Y (according to any corresponding embodiment described herein) substituted with one or more targeting moieties (according to any corresponding embodiment described herein).

[0258] The backbone unit Y of the monomeric unit comprising the targeting moiety may optionally differ (optionally significantly differ) in structure compared to the backbone units Y of the other monomeric units in the polymeric portion (according to any corresponding embodiment described herein).

[0259] In any embodiment described herein where m is at least 1, the polymeric portion comprises a monomeric unit comprising a targeting moiety, the monomeric unit being at the end of the polymeric portion distal to the lipid portion. In such an embodiment, the compound represented by general formula I has formula Ib. [ka] (In the formula, T is a monomeric unit comprising a targeting moiety (according to any corresponding embodiment described herein); X and T are [Y(-LZ)] n [Y] m -1, and X, Y, L, Z, n, and m are defined as in any embodiment described herein for Formula I, with the proviso that m is at least 1.

[0260] It should be understood that T in Formula Ib is a monomeric unit of the type represented by Y in Formula I and Formula Ia (i.e., lacking a pendant group represented by (-LZ)), and the number of monomeric units represented by Y other than T (i.e., lacking a pendant group represented by (-LZ)) is represented by the value m-1; thus, the total number of monomeric units (lacking a pendant group represented by (-LZ)), including T, is represented by the variable m as in Formula I and Formula Ia.

[0261] In some embodiments, m is 1, and thus m-1 is 0, and the compound represented by Formula Ib consequently has the formula: X-[Y(-LZ)] n -T, where L, T, X, Y, Z, and n are defined as in any embodiment described herein.

[0262] Preparation of a monomeric unit comprising a targeting moiety according to any corresponding embodiment described herein may optionally be carried out by preparing a monomer comprising the targeting moiety and using that monomer to prepare a polymeric moiety described herein (e.g., by polymerization of a monomer according to any corresponding embodiment described herein), and / or by modifying the monomeric unit in the polymeric moiety using any suitable technique known in the art, including but not limited to conjugation techniques, and then subsequently preparing a polymeric moiety (e.g., by polymerization of a monomer according to any corresponding embodiment described herein).

[0263] In some embodiments of any embodiment described herein with respect to a targeting moiety, the targeting moiety does not include a moiety having general formula II (according to any corresponding embodiment described herein). For example, it should be understood that even if a moiety represented by formula II has the ability to form a bond with a target as described herein, the phrase "targeting moiety" in some embodiments relates to a moiety that is distinct from the moiety represented by variable Z (having general formula II).

[0264] In some embodiments of any one of the embodiments described herein, the pendant group represented by (-LZ) is selected so as not to form a bond with the target and / or not to include the structure and / or properties of the targeting moiety as described herein in any one of the corresponding embodiments. For example, in embodiments in which a targeting moiety including a nucleophilic group (according to any corresponding embodiment described herein), e.g., an amine group, is capable of forming a bond (e.g., a covalent bond) with the target, variable Z (having general formula II) is optionally selected so that the depicted amine / ammonium group is a tertiary amine / ammonium (i.e., no more than two of R1-R3 are hydrogen) or a quaternary ammonium (i.e., none of R1-R3 are hydrogen), preferably a quaternary ammonium (e.g., containing a trimethylamino group, as in phosphocholine). Tertiary amine groups, and particularly quaternary ammonium groups, can be significantly less reactive nucleophiles than primary and secondary amine groups.

[0265] In some embodiments of any of the embodiments described herein with respect to a targeting moiety, the targeting moiety comprises (and optionally consists of) at least one functional group capable of forming a covalent or non-covalent bond (preferably a selective non-covalent bond) with a substance and / or material (which is referred to herein as a "target"), for example, to the surface of the target (e.g., the surface of a cell and / or tissue).

[0266] As used herein, the phrase "functional group" encompasses chemical groups and moieties of any size and any functionality described herein (e.g., any functionality capable of forming a covalent or non-covalent bond with a target).

[0267] Non-covalent binding according to any corresponding embodiment described herein may optionally be achieved by non-covalent interactions such as, without limitation, electrostatic attraction, hydrophobic bonding, hydrogen bonding, and aromatic interactions.

[0268] In some embodiments, the targeting moiety comprises a functional group capable of forming a selective non-covalent bond with a target, e.g., the affinity of the targeting moiety and / or functional group for the target (e.g., as determined based on the dissociation constant) is higher than the affinity of the targeting moiety and / or functional group for most (or all) other compounds capable of forming non-covalent bonds with the targeting moiety.

[0269] In some embodiments of any one of the embodiments described herein, the one or more functional groups are capable of forming covalent bonds with one or more specific functional groups (e.g., hydroxy, amine, thiohydroxy, and / or oxo groups) present on a target (e.g., on a target according to any corresponding embodiment described herein).

[0270] Examples of functional groups (on the targeting moiety) capable of forming covalent bonds with targets (according to any corresponding embodiment described herein) and the types of covalent bonds that the functional groups are capable of forming include, without limitation: For example, nucleophilic groups such as thiohydroxy, amines (e.g., primary or secondary amines) and hydroxy, which can form covalent bonds with nucleophilic leaving groups (e.g., any nucleophilic group described herein) on the target, Michael acceptors (e.g., any Michael acceptors described herein), acyl halides, isocyanates and / or isothiocyanates (e.g., as described herein); Nucleophilic leaving groups such as, for example, halo, azido (-N3), sulfate, phosphate, sulfonyl (e.g., mesyl, tosyl), N-hydroxysuccinimide (NHS) (e.g., NHS ester), sulfo-N-hydroxysuccinimide, and anhydrides, which can form covalent bonds with nucleophilic groups (e.g., as described herein) on a target; For example, Michael acceptors such as enones (e.g., maleimide, acrylate, methacrylate, acrylamide, methacrylamide), nitro groups, and vinyl sulfones, which can form covalent bonds with nucleophilic groups (e.g., as described herein) on the target, optionally thiohydroxy; For example, a dihydroxyphenyl group (according to any corresponding embodiment described herein) that can form a covalent bond with a nucleophilic group (e.g., as described herein) and / or a substituted or unsubstituted phenyl group (e.g., another dihydroxyphenyl group) on a target as described herein; For example, acyl halide (-C(=O)-halogen), isocyanate (-NCO) and isothiocyanate (-N=C=S) groups, which can form covalent bonds with nucleophilic groups (e.g., as described herein) on a target; For example, carboxylate (-C(=O)OH) groups may form covalent bonds with hydroxyl groups on the target to form ester bonds, and / or may form covalent bonds with amine groups (e.g., primary amines) on the target to form amide bonds (optionally by reaction with a coupling reagent such as a carbodiimide), and / or carboxylate groups may be present on the target to form amide or ester bonds, respectively, with amine or hydroxyl groups on the targeting moiety; an oxo group (optionally on an aldehyde group (-C(=O)H)) that can form a covalent imine bond with an amine group (e.g., a primary amine) on the target, and / or an oxo group (optionally on an aldehyde group) on the target that can form a covalent imine bond with an amine group on the targeting moiety; and / or A thiohydroxy group that can form a covalent disulfide (-SS-) bond with a thiohydroxy group on the target.

[0271] Optionally, modification of a monomer (e.g., before polymerization) or a monomeric unit of a polymer moiety (e.g., after polymerization) to include any of the functional groups described herein can be carried out using any technique suitable for conjugation known in the art. One of skill in the art will readily be able to select a suitable technique for modifying any given molecule.

[0272] As used herein, the term "dihydroxyphenyl" refers to an aryl group (as defined herein) that is phenyl substituted with two hydroxyl groups at any position thereof. The phenyl may optionally be substituted with additional substituents (which may optionally include additional hydroxyl groups), thereby forming a substituted dihydroxyphenyl group, or alternatively, the phenyl does not include any substituents other than the two hydroxyl groups, such that the dihydroxyphenyl group is an unsubstituted dihydroxyphenyl group.

[0273] In some embodiments of any one of the embodiments described herein, the dihydroxyphenyl group is ortho-dihydroxyphenyl (where the hydroxyl groups are attached to adjacent phenyl rings) or para-dihydroxyphenyl (where the hydroxyl groups are attached to opposite sides of the phenyl ring), each substituted or unsubstituted. In some such embodiments, the ortho-dihydroxyphenyl or para-dihydroxyphenyl is unsubstituted dihydroxyphenyl.

[0274] Dihydroxyphenyl groups according to any corresponding embodiment described herein may optionally be covalently and / or non-covalently bound to a target via any one or more of the binding mechanisms described for dihydroxyphenyl(catechol) groups in Lee et al. [PNAS 2006, 103:12999-13003], Brodie et al. [Biomedical Materials 2011, 6:015014] and / or International Patent Application No. PCT / IL2015 / 050606 (the contents of each of which are incorporated by reference in their entirety, particularly with respect to binding to surfaces formed by dihydroxyphenyl(catechol) groups).

[0275] In some embodiments of any one of the embodiments described herein, the functional group capable of forming a bond with the target is a functional group capable of forming a covalent bond with an amine group, optionally a primary amine group. In some such embodiments, the target comprises one or more amino acid residues, e.g., a peptide or polypeptide of any length (e.g., at least two amino acid residues, e.g., a protein), and the amine group may optionally be a lysine side chain amine group and / or an N-terminal amine group. In some embodiments, the target comprises an extracellular matrix protein, e.g., collagen. In some embodiments, the target comprises cartilage (e.g., articular cartilage).

[0276] In some embodiments of any one of the embodiments described herein, the targeting moiety comprises (and optionally consists of) at least one functional group capable of forming a non-covalent bond with a target (e.g., as described herein in any one of the corresponding embodiments).

[0277] In some embodiments of any one of the embodiments described herein, the functional group capable of forming a non-covalent bond with the target comprises (and optionally consists of) a polysaccharide and / or a polypeptide (e.g., a protein and / or a fragment thereof), wherein the target optionally comprises a polysaccharide and / or polypeptide ligand, and / or the target comprises a polysaccharide and / or a polypeptide (e.g., a protein and / or a fragment thereof) and the functional group capable of forming a non-covalent bond with the target is a polysaccharide and / or polypeptide ligand.

[0278] Examples of suitable polysaccharides and / or polypeptides and their ligands include, without limitation: avidin or streptavidin as the polypeptide described herein and biotin as its ligand; a polysaccharide-binding polypeptide as a polypeptide described herein and a complementary polysaccharide as its ligand (or a polypeptide that binds to a complementary polysaccharide as a ligand of a polysaccharide described herein); a collagen-binding polypeptide as a polypeptide described herein and a complementary collagen as its ligand (or a collagen as a polypeptide described herein and a complementary collagen-binding polypeptide as its ligand); A cell receptor expressed in a cell and a ligand to which the receptor selectively binds, an antibody against any antigen (e.g., where the target described herein optionally includes the antigen) or a fragment of such an antibody as a polypeptide described herein and the respective antigen as its ligand; and Antibody mimetics against any antigen (eg, where the targets described herein optionally include antigens).

[0279] Examples of cellular receptors expressed on cells include, without limitation, receptors characteristic of particular cell types and / or tissues and receptors overexpressed on cancer cells. The cellular receptor or cell is optionally a target as described herein, and the targeting moiety optionally includes any ligand of the receptor. Examples of such ligands include, without limitation, transferrin, a ligand of the transferrin receptor that can optionally target the transferrin receptor, which is overexpressed in some cancer cells; keratinocyte growth factor (KGF or FGF7), which is specific to cells of epithelial origin and can optionally target the KGF receptor, which is overexpressed in endometrial or pancreatic cancer [Visco et al., Int J Oncol 1999, 15:431-435; Siegfried et al., Cancer 1997, 79:1166-1171]; and epidermal growth factor (EGF), which can optionally target the EGF receptor, such as that overexpressed in glioma and endometrial cancer, optionally erbB [Normanno et al., Curr Drug Targets 2005, 6:243-257].

[0280] As used herein, the term "antibody" encompasses any type of immunoglobulin.

[0281] As used herein, the phrase "antibody mimetics" includes any type of molecule, optionally a polypeptide, said in the art to have the ability to selectively (e.g., non-covalently) bind to an antigen. Non-limiting examples of antibody mimetics include, for example, those described by Nygren [FEBS J 2008, 275:2668-2676], Ebersbach et al. [J Mol Biol 2007, 372:172-185], Johnson et al. [Anal Chem 2012, 84:6553-6560], Krehenbrink et al. [J Mol Biol 2008, 383:1058-1068], Desmet et al. [Nature Comm 2014, 5:5237], Skerra [FEBS J 2008, 275:2677-2683], Silverman et al. [Nature Biotechnol 2005, 23:1556-1561], Stumpp et al. [Drug Discovery Today 2008, 13:695-701], Grabulovski et al. [J Biol Chem 2007, 282:3196-3204], Nixon & Wood [Curr Opin Drug Discov Devel 2006, 9:261-268], Koide & Koide [Methods Mol Biol 2007, 325:95-109] and Gebauer & Skerra [Curr Opin Chem Biol 2009, 13:245-255] (the contents of each of which are incorporated by reference in their entirety, particularly with respect to their content relating to particular types of antibody mimetics).

[0282] As used herein, the phrase "polysaccharide-binding polypeptide" encompasses any polypeptide or oligopeptide (a peptide chain at least 2, preferably at least 4 amino acid residues in length) capable of selectively (e.g., non-covalently) binding to a polysaccharide. A wide variety of polysaccharide-binding polypeptides and their binding specificities are known to those skilled in the art and include short peptide sequences (e.g., 4-50, optionally 4-20 amino acid residues in length) and longer polypeptides such as proteins or fragments thereof (e.g., carbohydrate-binding modules and / or domains). In addition, the phrase "polysaccharide-binding polypeptide" encompasses antibodies capable of specifically binding to a polysaccharide. Such antibodies will be available to those skilled in the art and / or will know how to prepare such antibodies using immunological techniques known in the art.

[0283] Examples of polysaccharide-binding polypeptides that may be used in some of the embodiments of any one of the present invention include, without limitation, carbohydrate-binding modules (CBMs); and hyaluronic acid-binding peptides, polypeptides, and / or modules (see, e.g., WO 2013 / 110056, WO 2014 / 071132, Barta et al. [Biochem J 1993, 292:947-949], Kohda et al. [Cell 1996, 86:767-775], Brisset & Perkins [FEBS Lett 1996, 388:211-216], Peach et al. [J Cell Biol 1993, 122:257-264], Singh et al. [Nature Materials 2014, 13:988-995], and Zaleski et al. [Antimicrob Agents Chemother 1996, 13:988-995]). 2006, 50:3856-3860] (the contents of each of which are incorporated by reference in their entirety, particularly with respect to the content relating to certain polysaccharide-binding polypeptides, e.g., GAHWQFNALTVR (hyaluronic acid-binding peptide sequence)).

[0284] Examples of CBMs that may be used in some of the embodiments of any one of the present invention include, without limitation, CBMs belonging to the family CBM3, CBM4, CBM9, CBM10, CBM17 and / or CBM28 (which may optionally be used for binding to cellulose, e.g., in cellulose-containing targets); CBM5, CBM12, CBM14, CBM18, CBM19 and / or CBM33 (which may optionally be used for binding to chitin and / or other N-acetylglucosamine-containing polysaccharides, e.g., in chitin-containing targets); CBM15 (which may optionally be used for binding to hemicellulose, e.g., in hemicellulose-containing targets); and / or CBM20, CBM21 and / or CBM48 (which may optionally be used for binding to starch and / or glycogen, e.g., in starch-containing and / or glycogen-containing targets).

[0285] As used herein, the phrase "collagen-binding polypeptide" encompasses any polypeptide or oligopeptide (a peptide chain of at least two, preferably at least four, amino acid residues in length) capable of selectively (e.g., non-covalently) binding to collagen (e.g., one type of collagen, several types of collagen, or all types of collagen), including glycosylated polypeptides and oligopeptides such as peptidoglycans and proteoglycans. A wide variety of collagen-binding polypeptides and their binding specificities are known to those of skill in the art and include short peptide sequences (e.g., 4-50, optionally 4-20 amino acid residues in length) and longer polypeptides such as proteins or fragments thereof (e.g., collagen-binding domains). In addition, the phrase "collagen-binding polypeptide" encompasses antibodies capable of specifically binding to collagen. Such antibodies are available to those of skill in the art and / or the skilled artisan would know how to prepare such antibodies using immunological techniques known in the art.

[0286] Examples of collagen-binding polypeptides that may be used in embodiments of the present invention include, without limitation, collagen-binding proteins (e.g., decorin), fragments thereof, and / or other polypeptides as described in U.S. Pat. No. 8,440,618, Abd-Elgaliel & Tung [Biopolymers 2013, 100:167-173], Paderi et al. [Tissue Eng Part A 2009, 15:2991-2999], Rothenfluh et al. [Nat Mater 2008, 7:248-254], and Helms et al. [J Am Chem Soc 2009, 131:11683-11685] (the contents of each of which are incorporated by reference in their entirety, particularly with respect to particular collagen-binding polypeptides, e.g., the sequence WYRGRL).

[0287] It is expected that many relevant binding functional groups and moieties will be developed and / or discovered during the life of this application until the expiration of the patent, and it is intended that all such new technologies be included a priori within the scope of the terms "targeting moiety," "functional group," "cellular receptor," "antibody," "antibody mimetics," "collagen-binding polypeptide," and "polysaccharide-binding polypeptide," etc.

[0288] In some embodiments of any embodiment described herein, the functional group of the targeting moiety (according to any corresponding embodiment described herein) is attached to a linking group (as defined herein). The linking group may optionally be any linking group or moiety described herein, including, but not limited to, substituted or unsubstituted hydrocarbons. In some embodiments, the targeting moiety (optionally a substituent of backbone unit Y) consists essentially of a functional group attached to the remainder of the polymer segment via a linking group.

[0289] The functional group may optionally be attached to a linking moiety by a covalent bond achievable by reaction between two functional groups, such as any of the covalent bonds and / or functional groups described herein in connection with forming a covalent bond between a functional group and a target.

[0290] In some embodiments of any of the embodiments described herein with respect to functional groups comprising peptides or polypeptides, amino acid residues of the peptides or polypeptides are optionally linked to the linking group of the targeting moiety, for example, by an amide bond formed between an amine or carboxylate group on the peptide or polypeptide (e.g., on the N-terminus, lysine side chain, C-terminus, glutamic acid side chain, and / or aspartic acid side chain), an ester bond formed between a hydroxyl or carboxylate group on the peptide or polypeptide (e.g., on the serine side chain, threonine side chain, C-terminus, glutamic acid side chain, and / or aspartic acid side chain), and / or a disulfide bond formed between a thiohydroxy group on the peptide or polypeptide (e.g., on a cysteine ​​side chain). In some embodiments, the amino acid residues linked to the linking group are N- and / or C-terminal residues, e.g., any amino acid residue linked via its N-terminal amino group or C-terminal carboxylate group, and / or terminal lysine, glutamic acid, aspartic acid, serine, threonine, and / or cysteine ​​residues linked via their side chains.

[0291] In some embodiments, amino acid residues and / or peptides (e.g., 2-20 amino acid residues in length) are added to the N-terminus and / or C-terminus of a peptide or polypeptide sequence of a functional group (according to any corresponding embodiment described herein) to link said sequence to a linking group. Examples of such terminal amino acid residues and / or peptides include, without limitation, glycine residues and peptides with a terminal glycine residue (according to any corresponding embodiment described herein) which may be used to attach a linking group to the N-terminus or C-terminus; serine and threonine residues and a terminal serine or threonine residue (according to any corresponding embodiment described herein) which may be used to attach a linking group to the hydroxyl group of the serine or threonine side chain, optionally via an ester bond; and cysteine ​​residues and peptides with a terminal cysteine ​​residue (according to any corresponding embodiment described herein) which may be used to attach a linking group to the peptide via a disulfide bond.

[0292] In some embodiments, attaching a peptide or polypeptide to a linking group via a terminal amino acid residue minimizes interference (e.g., steric interference) with the functionality of the peptide or polypeptide after attachment to the linking group.

[0293] In some embodiments, attachment of a peptide or polypeptide to a linking group via a terminal glycine facilitates conjugation by minimizing interference (e.g., steric interference) from the amino acid side chain (which lacks glycine) upon attachment to the linking group.

[0294] According to some of the optional embodiments described herein, the polymeric compound is as described in commonly assigned U.S. Provisional Patent Application No. 63 / 402,097, which is incorporated by reference as if set forth in its entirety herein.

[0295] Bilayer-forming lipids and liposomes: As described herein, liposomes according to embodiments include, among other things, at least one bilayer-forming lipid.

[0296] As used herein, the term "bilayer-forming lipid" encompasses any compound that can form a bilayer comprising two parallel layers of molecules of the compound (called "lipid") from a pure aqueous solution of the compound.

[0297] Typically, the bilayer (e.g., in a liposome according to some of the embodiments described herein) comprises relatively polar portions of the lipids at the two surfaces of the bilayer, which may optionally constitute an interface with aqueous solution and / or an interface with a solid surface, and relatively hydrophobic portions of the lipids at the interior of the bilayer, at the interface between the two layers of lipid molecules that form the bilayer.

[0298] Examples of bilayer-forming lipids include glycerophospholipids. Suitable examples of glycerophospholipids include, without limitation, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol.

[0299] It should be understood that the polymeric compound comprised by the liposome (according to any corresponding embodiment described herein) may optionally be a bilayer-forming lipid capable of forming a bilayer by itself or in combination with one or more additional bilayer-forming lipids.

[0300] In some embodiments of any one of the embodiments described herein, the bilayer-forming lipid comprises at least one charged group (e.g., one or more negatively charged groups and / or one or more positively charged groups).

[0301] In some embodiments, the bilayer-forming lipids are zwitterionic and contain both (eg, equal numbers of) negatively and positively charged groups (eg, one of each).

[0302] In some embodiments of any of the embodiments described herein, the molar ratio of bilayer-forming lipids (included in addition to the polymeric compound) to polymeric compound (according to any corresponding embodiment described herein) in the liposome is in the range of 5:1 to 5,000:1 (bilayer-forming lipids:polymeric compound), optionally in the range of 10:1 to 2,500:1, optionally in the range of 25:1 to 1,000:1, and optionally in the range of 50:1 to 500:1, including any intermediate values ​​and subranges therebetween.

[0303] In some embodiments of any of the embodiments described herein with respect to bilayers, the molar ratio of bilayer-forming lipids (included in addition to the polymeric compound) to polymeric compound in the bilayer is in the range of 10:1 to 1,000:1 (bilayer-forming lipids:polymeric compound), optionally in the range of 10:1 to 500:1, optionally in the range of 10:1 to 200:1, and optionally in the range of 10:1 to 150:1, including any intermediate values ​​and subranges therebetween.

[0304] In some embodiments of any of the embodiments described herein with respect to bilayers, the molar ratio of bilayer-forming lipids (included in addition to the polymeric compound) to polymeric compound in the bilayer is in the range of 10:1 to 100:1 (bilayer-forming lipids:polymeric compound), optionally in the range of 10:1 to 50:1, optionally in the range of 20:1 to 40:1, including any intermediate values ​​and subranges therebetween.

[0305] In some embodiments of any of the embodiments described herein with respect to bilayers, the molar ratio of bilayer-forming lipids (included in addition to the polymeric compound) to polymeric compound in the bilayer is in the range of 10:1 to 1,000:1 (bilayer-forming lipids:polymeric compound), optionally in the range of 100:1 to 1,000:1, optionally in the range of 101:1 to 500:1, and optionally in the range of 100:1 to 200:1, including any intermediate values ​​and subranges therebetween.

[0306] Throughout this specification, the terms "mol ratio" and "molar ratio" are used interchangeably and refer to the ratio between the mole percentages of the indicated components in a lipid bilayer or liposome.

[0307] Bilayers according to embodiments described herein can optionally be self-closed (e.g., such that the bilayer has no edges), thereby forming an interior volume separated from the surrounding environment by the bilayer, which is referred to herein and in the art as a "liposome." Alternatively or additionally, the bilayer can be open and / or have edges.

[0308] As used herein and in the art, the term "liposome" refers to an artificially prepared vesicle comprising a bilayer composed of amphiphilic lipid molecules. In an aqueous medium, the bilayer is typically configured such that the hydrophilic portions of the amphiphilic lipids are exposed to the medium on both surfaces of the bilayer, while the lipophilic portions of the lipids are located in the inner portion of the bilayer and are therefore less exposed to the medium. Examples of liposomes that can be used in any one of the embodiments described herein include, without limitation, small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs), and large multilamellar vesicles (MLVs).

[0309] Liposomes according to embodiments as described herein comprise, inter alia, at least one bilayer-forming lipid.

[0310] It is understood that the polymeric compound comprised in the liposome (according to any corresponding embodiment described herein) may optionally be a bilayer-forming lipid capable of forming a bilayer by itself or in combination with one or more additional bilayer-forming lipids.

[0311] Liposomes may optionally comprise a single bilayer (e.g., unilamellar vesicles) or multiple bilayers (e.g., multilamellar vesicles), where each bilayer optionally independently forms a closed vesicle, e.g., comprising concentric bilayer vesicles and / or multiple individual bilayer vesicles contained within the same bilayer vesicle.

[0312] As used herein, the term "unilamellar" refers to a liposome characterized by a single lipid bilayer, while the term "multilamellar" refers to a liposome characterized by multiple lipid bilayers, e.g., concentric bilayers.

[0313] As used herein, the phrase "small unilamellar vesicles" refers to unilamellar liposomes having a diameter of less than 100 nm, while the phrase "large unilamellar vesicles" refers to unilamellar liposomes having a diameter of at least 100 nm.

[0314] In some embodiments of any one of the embodiments described herein, the liposomes comprise multilamellar vesicles, hi some embodiments, the liposomes are predominantly (greater than 50 weight percent) multilamellar vesicles.

[0315] In some embodiments, the liposomes are predominantly (greater than 50 percent by weight) large multilamellar vesicles (MLVs) of at least 100 nm in diameter.

[0316] Liposomes according to any corresponding embodiment described herein may be approximately spherical in shape, or may assume some other shape, such as elongated tubes and / or flattened (e.g., sheet-like) shapes.

[0317] In some of the embodiments described herein, the weight ratio of bilayer-forming lipid to polymeric compound is within the range of 2:1 to 1,000:1, or 2:1 to 500:1, or 2:1 to 100:1, or 2:1 to 50:1, or 2:1 to 20:1.

[0318] In some of the embodiments described herein, the average diameter of the liposomes is within the range of about 50 nm to about 5,000 nm, or about 500 nm to about 5,000 nm, or about 500 nm to about 4,000 nm, or about 500 nm to about 3,500 nm, including any intermediate values ​​and subranges therebetween.

[0319] In some of the embodiments described herein, the average diameter of the liposomes is within the range of about 100 nm to about 2,000 nm, or about 100 nm to about 1,000 nm, or 200 nm to 2,000 nm, or 200 nm to 1,000 nm, about 500 nm to about 1,000 nm, or 400 to about 800 nm, including any intermediate values ​​and subranges therebetween.

[0320] The mean diameter according to any corresponding embodiment described herein can optionally be the arithmetic mean (ratio of the sum of the values ​​to the number of values) or the Z-average (shortened to the intensity-weighted harmonic mean) as that term is defined in the art of dynamic light scattering. In exemplary embodiments, the mean diameter is the Z-average diameter determined by dynamic light scattering.

[0321] The polydispersity index (PDI) and / or mean diameter of the liposomes in the composition can optionally be determined by dynamic light scattering (e.g., using commercially available equipment) using a two-parameter fit to the data (e.g., according to ISO 13321 and ISO 22412 standards) to determine the PDI and Z-average diameter.

[0322] In some of the embodiments described herein, the PDI of the liposomes is less than 1 or less than 0.8, for example, in the range of 0.3 to 1, or 0.3 to 0.8, or 0.3 to 0.6, including any intermediate values ​​and subranges therebetween.

[0323] In some of the embodiments described herein, the zeta potential of the liposome is at least −3 mV (ie, −3 mV or more negative), optionally at least −3.5 mV, and optionally at least −4 mV.

[0324] In some of the embodiments described herein, the zeta potential of the liposome is in the range of 10 mV to -10 mV (e.g., 5 mV to -5 mV), optionally in the range of 0 to -10 mV (e.g., 0 to -5 mV or -3 mV to -5 mV).

[0325] The zeta potential can be determined using any suitable technique known in the art, such as electrophoretic light scattering (e.g., using a commercially available instrument). The zeta potential of liposomes can be determined by diluting the liposomes in an aqueous salt solution (e.g., NaCl) of a predetermined salt concentration (e.g., 10 μM).

[0326] In some embodiments of any of the embodiments described herein with respect to liposomes, the liposome further comprises at least one functional moiety or agent attached to the surface of the liposome and / or located within the lipid bilayer and / or core of the liposome (e.g., located within and / or enveloped by the liposome bilayer).

[0327] Examples of functional moieties and agents suitable for inclusion in the embodiments described herein include, without limitation, therapeutically active agents or portions of therapeutically active agents (e.g., where the active agent is releasable upon cleavage of the moiety), labeling moieties or agents, and / or targeting moieties or agents (e.g., targeting moieties or agents on the surface of the liposome).

[0328] Examples of therapeutically active agents suitable for inclusion in liposomes (e.g., as a drug molecule or moiety) include, without limitation, amphotericin B, cisplatin, cytarabine, daunorubicin, doxorubicin, estradiol, influenza virosomes, morphine, surfactant protein B, surfactant protein C, verteporfin, and vincristine.

[0329] In some of any of the embodiments described herein, the liposomes optionally include a therapeutically active agent incorporated within and / or on the surface of the liposome. In some such embodiments, the therapeutically active agent is a therapeutically active agent described in WO 2018 / 150429, which is incorporated herein by reference.

[0330] In some of any of the embodiments described herein, the liposomes lack a therapeutically active agent.

[0331] As used herein, the phrase "therapeutically active agent" refers to any agent (e.g., a compound) having a therapeutic effect, provided that the compound is not a bilayer-forming lipid or polymeric compound contained in a liposome (according to any corresponding embodiment described herein), and refers to any portion of an agent (e.g., a portion of a compound), including a portion of a bilayer-forming lipid or polymeric compound, that yields the agent with a therapeutic effect upon release (e.g., upon cleavage of one or more covalent bonds). Thus, while bilayer-forming lipids and polymeric compounds themselves are excluded from the definition of therapeutically active agent, the bilayer-forming lipids and / or polymeric compounds may optionally contain or yield a therapeutically active agent upon release, in which case the portion of the bilayer-forming lipid and / or polymeric compound that yields the therapeutically active agent is also considered a therapeutically active agent as defined herein.

[0332] When associated with liposomes, therapeutically active agents may optionally be bound to the liposomes (e.g., to the outer and / or inner surfaces of the liposome membrane) by covalent or non-covalent (e.g., electrostatic and / or hydrophobic) bonds, may be incorporated into the liposome membrane (e.g., a lipophilic agent stably partitioned into the lipid phase of the liposome), and / or may be entrapped in the liposome core (e.g., a hydrophilic agent in the aqueous component of the liposome). The therapeutically active agent may optionally be a moiety covalently bound to the liposome (e.g., a moiety bound to a lipid to form a lipid derivative containing the moiety). Such binding may, in some embodiments, be achieved using techniques known in the art (e.g., amide bond formation).

[0333] According to some of the embodiments described herein, the composition comprises a plurality of liposomes, at least some of which comprise a plurality of liposomes as defined herein. Optionally, the composition comprises an additional portion of liposomes other than those described herein (e.g., which do not comprise a polymeric compound as described herein).

[0334] Examples of labeling moieties or agents include chromogenic (e.g., that absorb visible light), fluorescent, phosphorescent, and / or radioactive moieties and compounds. Many such compounds and moieties (and techniques for preparing such moieties) will be known to those of skill in the art.

[0335] The targeting moiety in the liposome according to any corresponding embodiment described herein can optionally be a targeting moiety according to any corresponding embodiment described herein. The targeting moiety in the liposome can be included in a polymeric compound (according to any corresponding embodiment described herein) according to some embodiments of the invention, where the liposome comprises the polymeric compound. Alternatively or in addition, the targeting moiety in the liposome can optionally be included in another compound in the liposome, where optionally a bilayer-forming lipid (according to any corresponding embodiment described herein) is conjugated to the targeting moiety according to any corresponding embodiment described herein.

[0336] As used herein, a "targeting agent" refers to a compound ("agent") that includes (and optionally consists essentially of) a targeting moiety according to any corresponding embodiment described herein (e.g., in reference to a targeting moiety included in a polymeric compound described herein). Typically, the phrase "targeting agent" is used to refer to a compound other than a polymeric compound that includes a targeting moiety, as described herein.

[0337] In some embodiments, the functional moiety (e.g., targeting or labeling moiety) is covalently attached to the liposome, which in some embodiments may be achieved using techniques known in the art (e.g., amide bond formation).

[0338] Composition and Use: It should be noted that the liposomes disclosed herein that are part of a cosmetic composition may be considered carriers for active ingredients (e.g., humectants, skin protectants), skin permeation regulators, and / or other formulation ingredients.

[0339] The cosmetic or cosmeceutical composition (also interchangeably referred to herein as a formulation) according to the present embodiments can be used as a cosmetic or cosmeceutical product (e.g., a skin care product) itself, or can be used to make such a product.

[0340] In some embodiments of the present invention, the cosmetic or cosmeceutical preparation is formulated in a form suitable for topical application to an area of ​​application (eg, keratinous tissue, such as facial skin).

[0341] As described in more detail below, by selecting an appropriate carrier and other ingredients that can optionally be included in the formulation, the compositions of the present embodiments can be formulated into any form typically used for topical application.

[0342] By "suitable carrier" for topical application is meant any medium that has color, odor, and a refreshing sensation, does not cause unacceptable discomfort (stinging, stiffness, or redness), and is compatible with keratin substrates or mucosal tissues.

[0343] According to some embodiments of any of these aspects of the invention, the formulation further comprises a cosmetically or cosmeceutical acceptable carrier.

[0344] As used herein, the term "cosmetic or cosmeceutical acceptable carrier" refers to a carrier or diluent that does not cause significant irritation to keratinous materials or tissues of living organisms and does not neutralize the biological activity and properties of the applied compound or combination of compounds (e.g., liposomes as described herein). Examples of carriers include, without limitation, propylene glycol, water, saline, emulsions, and mixtures of organic solvents and water, as well as solid (e.g., powdered) and gaseous carriers. The carrier is typically intended to facilitate topical application of the composition to keratinous tissues or substrates. It should be noted that the carrier is selected according to the intended use and the form of the formulation or product containing it, and is not limited to the above description.

[0345] According to some of the embodiments described herein, the carrier comprises an aqueous liquid, such as water or an aqueous solution. According to some embodiments, liposomes are included in the aqueous liquid and liposome-containing aqueous liquid incorporated into the composition.

[0346] A cosmetic or cosmeceutical formulation as described herein for any corresponding embodiment and any combination thereof may be packaged in a packaging material and may be identified in or on the packaging material with text for use in treating a medical or cosmetic condition, as described in more detail below. Depending on its consistency, the packaging may be adapted for topical application of the formulation. For example, liquid formulations (including emulsions and oils) may be packaged in a container equipped with a means for topically applying the formulation, such as a nozzle, dropper, or pipette, or in a narrow-mouthed and / or squeezable bottle. Formulations in the form of a spray or aerosol may be packaged in a container equipped with a nozzle and / or mechanism for atomization. Ointments, gels, oils, and creams may be packaged in a simple container or in a squeezable container.

[0347] According to an aspect of some embodiments of the present invention, there is provided an article of manufacture comprising any formulation and / or product as described herein, and optionally a means for topically applying the formulation (e.g., as described herein).

[0348] "Topical application" means applying or spreading the formulation, composition or product of the present embodiments onto the surface of keratinous tissue.

[0349] In some embodiments, the formulations as described are in the form of a cream, ointment, paste, gel, lotion, milk, suspension, solution, aerosol, spray, foam, serum, or mousse.

[0350] The formulations may be water-based or emulsion-based (including water-in-oil, oil-in-water, water-in-oil-in-water and oil-in-water-in-oil emulsions) or silicone-based.

[0351] Ointments are semi-solid preparations typically based on petrolatum or petroleum derivatives. The specific ointment base to be used will provide optimal delivery of the active agent selected for a given formulation, and preferably also provide other desired properties (e.g., skin emollience). Like other carriers or vehicles, ointment bases must be inert, stable, non-irritating, and non-sensitizing. As explained in Remington: The Science and Practice of Pharmacy, 19th Ed., Easton, Pa.: Mack Publishing Co. (1995), pp. 1399-1404, ointment bases can be divided into four classes: oleaginous bases, emulsifiable bases, emulsifiable bases, and water-soluble bases. Oleaginous ointment bases include, for example, vegetable oils, fats obtained from animals, and semi-solid hydrocarbons obtained from petroleum.

[0352] Emulsifiable ointment bases, also known as absorbent ointment bases, contain little or no water and include, for example, hydroxystearin sulfate, anhydrous lanolin, and hydrophilic petrolatum. Emulsion ointment bases are either water-in-oil (W / O) emulsions or oil-in-water (O / W) emulsions and include, for example, cetyl alcohol, glyceryl monostearate, lanolin, and stearic acid. Preferred water-soluble ointment bases are prepared from polyethylene glycols of various molecular weights.

[0353] Lotions are preparations that are applied to the skin surface without friction. Lotions are typically liquid or semi-liquid preparations, with solid particles, including sunscreen capsules, in a water or alcohol base. Lotions are typically preferred for covering / protecting large areas of the body due to the ease of application of the highly fluid composition. Lotions are typically suspensions of solids, often containing liquid oily emulsions of the oil-in-water type. Generally, insoluble materials in lotions must be finely divided. Lotions typically contain suspending agents to create better dispersion, as well as compounds useful for localizing and maintaining the active agent in contact with the skin, such as methylcellulose and sodium carboxymethylcellulose.

[0354] Creams are viscous liquids or semi-solid emulsions, either oil-in-water or water-in-oil. Cream bases are typically water-washable and contain an oil phase, an emulsifier, and an aqueous phase. The oil phase, also called the "internal" phase, generally contains petrolatum and / or a fatty alcohol such as cetyl or stearyl alcohol and / or a natural oil substance and / or a plant extract. The aqueous phase typically, although not necessarily, exceeds the oil phase in volume and generally contains a humectant. The emulsifier in a cream formulation is generally a nonionic, anionic, cationic, or amphoteric surfactant. For further information, see Remington: The Science and Practice of Pharmacy, supra.

[0355] Pastes are semi-solid dosage forms in which a bioactive agent is suspended in a suitable base. Depending on the nature of the base, pastes can be divided into fatty pastes or those made of a single-phase aqueous gel. The base in fatty pastes is generally petrolatum, hydrophilic petrolatum, etc. Pastes made of a single-phase aqueous gel are generally formulated with a base such as carboxymethylcellulose. For further information, reference can be made to Remington: The Science and Practice of Pharmacy.

[0356] Gel formulations are semi-solid suspension-type systems. Single-phase gels contain organic polymers substantially uniformly distributed throughout a carrier liquid, typically aqueous, but preferably also containing alcohol and, optionally, oil. Preferred organic polymers, i.e., gelling agents, are cross-linked acrylic acid polymers, such as the carbomer polymer family, for example, carboxypolyalkylenes, commercially available under the trademark Carbopol™. Other preferred polymers in this context are hydrophilic polymers such as polyethylene oxides, polyoxyethylene-polyoxypropylene copolymers, and polyvinyl alcohol; cellulose-based polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and methylcellulose; gums such as tragacanth and xanthan gum; sodium alginate; and gelatin. To prepare a uniform gel, a dispersing agent such as alcohol or glycerin may be added, or the gelling agent may be dispersed by trituration, mechanical mixing, stirring, or a combination thereof.

[0357] Sprays generally provide the active agent in an aqueous and / or alcoholic solution, which can be delivered by misting the skin. Such sprays include those formulated to result in a concentrated active agent solution at the administration site after delivery; for example, the spray solution can be composed primarily of alcohol or other similar volatile liquids capable of dissolving the active agent. Upon delivery to the skin, the carrier evaporates, leaving the concentrated active agent at the administration site.

[0358] Foam compositions are typically formulated in a single-phase or multi-phase liquid form and housed in a suitable container, optionally with a propellant that facilitates the composition being pressed from the container and thus converted into a foam upon application. Other foam-forming techniques include, for example, "bag-in-can" formulation techniques. Compositions formulated in this manner typically contain a low-boiling hydrocarbon, such as isopropane. When such compositions are applied at body temperature and stirred, evaporation of the isopropane and foam formation occur, similar to pressurized aerosol foam-forming systems. Foams can be aqueous or hydroalcoholic, but are typically formulated with a high alcohol content, which rapidly evaporates upon application to the user's skin, driving the active ingredient through the top skin layers to the treatment site.

[0359] According to a particular embodiment, the composition may comprise an aqueous phase.

[0360] The aqueous phase of the composition according to the invention comprises water and optionally a water-soluble solvent.

[0361] In the present invention, the term "water-soluble solvent" refers to a compound that is liquid at room temperature and miscible with water (greater than 50% by weight miscibility in water at 25° C. and atmospheric pressure).

[0362] The water-soluble solvents that may be used in the compositions of the present invention may also be volatile.

[0363] Among the water-soluble solvents that may be used in the compositions according to the invention, mention may be made in particular of lower monoalcohols having 2 to 8 carbon atoms, such as ethanol and isopropanol, glycols having 2 to 8 carbon atoms, such as ethylene glycol, propylene glycol, 1,3-butylene glycol and dipropylene glycol, C3 and C4 ketones and C2 to C4 aldehydes.

[0364] The aqueous phase (water and optionally water-miscible solvent) may be present in the composition in a content ranging from 20% to 95% by weight, better still from 30% to 80% by weight relative to the total weight of the composition.

[0365] According to another embodiment variant, the aqueous phase of the composition according to the invention may comprise at least one C2 to C32 polyol.

[0366] For the purposes of the present invention, the term "polyol" should be understood to mean any organic molecule containing at least two free hydroxyl groups.

[0367] Preferably, the polyols in the present invention are in liquid form at room temperature.

[0368] Polyols suitable for use in the present invention may be compounds of the linear, branched or cyclic, saturated or unsaturated alkyl type, carrying at least two -OH functional groups on the alkyl chain, particularly at least three -OH functional groups and more particularly at least four -OH functional groups.

[0369] Advantageously, the polyols suitable for formulating the compositions according to the invention are in particular those presenting from 2 to 32 carbon atoms, preferably from 3 to 16 carbon atoms.

[0370] Advantageously, the polyol may be chosen from polyglycerols such as, for example, ethylene glycol, pentaerythritol, trimethylolpropane, propylene glycol, 1,3-propanediol, butylene glycol, isoprene glycol, pentylene glycol, hexylene glycol, glycerol, glycerol oligomers, for example diglycerol and polyethylene glycols, and mixtures thereof.

[0371] According to a preferred embodiment of the invention, the polyol is selected from ethylene glycol, pentaerythritol, trimethylolpropane, propylene glycol, glycerol, polyglycerols and polyethylene glycols, and mixtures thereof.

[0372] According to a particular embodiment, the composition of the present invention may comprise at least propylene glycol.

[0373] According to another particular embodiment, the composition of the present invention may comprise at least glycerol.

[0374] Water suitable for the present invention may be floral water, such as cornflower water, and / or mineral water, such as water from Vittel, Lucas or La Roche Posay, and / or thermal water.

[0375] According to a specific embodiment, the composition comprises an alcohol.

[0376] According to a detailed aspect of the invention, the composition contains at least one monoalcohol containing from 2 to 8 carbon atoms.

[0377] According to a detailed aspect of the invention, the composition contains 0.5% to 10%, preferably 1 to 5%, by weight relative to the total weight of at least one monoalcohol containing 2 to 8 carbon atoms.

[0378] The composition of the present invention comprises at least one monoalcohol having from 2 to 8 carbon atoms, in particular from 2 to 6 carbon atoms, in particular from 2 to 4 carbon atoms.

[0379] The compositions of the present invention may include one or more monoalcohols.

[0380] The monoalcohol can be represented, for example, by the formula RaOH, where Ra is a linear or branched alkyl group containing 2 to 8 carbon atoms.

[0381] The monohydric alcohol includes ethanol, isopropanol, propanol, or butanol.

[0382] According to one embodiment, the composition of the present invention comprises ethanol.

[0383] Any of the formulations or products described herein can include additional agents and / or additives.

[0384] Some non-limiting representative examples of additives and / or agents include humectants, antioxidants, solvents, deodorants, fragrances, deodorants, antiperspirants, sunscreens (e.g., ultraviolet light blockers, UV filters), sunless tanning agents, hair conditioners, pH adjusters, chelating agents, preservatives, emulsifiers, vaso-occlusive agents, emollients, thickeners, solubilizers, permeation enhancers, anti-irritants, colorants or coloring agents (pigments, pearlizing agents, water-soluble dyes), propellants, surfactants, dispersants, fillers, and bactericides.

[0385] Representative examples of humectants include, without limitation, guanidine, glycolic acid and glycolate salts (e.g., ammonium salts and quaternary alkylammonium salts), aloe vera in any of its various forms (e.g., aloe vera gel), allantoin, urasol, polyhydroxy alcohols, such as sorbitol, glycerol, hexanetriol, polyethylene glycols such as propylene glycol, butylene glycol, hexylene glycol, sugars and starches, sugar and starch derivatives (e.g., alkoxylated glucose), hyaluronic acid, lactamide monoethanolamine, acetamide monoethanolamine, and any combination thereof.

[0386] Suitable pH adjusting agents include, for example, one or more of adipic acid, glycine, citric acid, calcium hydroxide, magnesium aluminometasilicate, a buffer, or any combination thereof.

[0387] Representative examples of deodorants include, without limitation, quaternary ammonium compounds such as cetyltrimethylammonium bromide, cetylpyridinium chloride, benzethonium chloride, diisobutylphenoxyethoxyethyldimethylbenzylammonium chloride, sodium N-lauryl sarcosine, sodium N-palmitoyl sarcosine, lauroyl sarcosine, N-myristoyl glycine, potassium N-lauryl sarcosine, stearyl, trimethylammonium chloride, sodium aluminum chlorohydroxylactate, tricetylmethylammonium chloride, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, diaminoalkylamides such as L-lysine hexadecylamide, heavy metal salts of citric acid, salicylic acid and piroctose, particularly the zinc salts and heavy metal salts of these acids, pyrithione, particularly zinc pyrithione and zinc phenol sulfate.

[0388] Other deodorizing agents include, without limitation, odor eliminating materials such as carbonates and bicarbonates, e.g., alkali metal carbonates and bicarbonates, ammonium and tetraalkylammonium carbonates and bicarbonates, particularly sodium and potassium salts, or any combination of the above.

[0389] The compositions of the present invention may incorporate antiperspirants in either solubilized or particulate form, including, for example, aluminum or zirconium astringent salts or complexes.

[0390] Representative examples of sunless tanning agents include, without limitation, dihydroxyacetone, glyceraldehyde, indoles and their derivatives. Sunless tanning agents can be used in combination with sunscreens.

[0391] A chelating agent is optionally added to the formulation to enhance the preservative or preservative system. Preferred chelating agents are weak agents such as ethylenediaminetetraacetic acid (EDTA), EDTA derivatives, or any combination thereof.

[0392] Suitable preservatives include, without limitation, one or more alkanols, disodium EDTA (ethylenediaminetetraacetate), EDTA salts, EDTA fatty acid conjugates, isothiazolinones, parabens such as methylparaben and propylparaben, propylene glycols, sorbates, urea derivatives such as diazolidinyl urea, or any combination thereof.

[0393] Suitable emulsifiers include, for example, one or more sorbitans, alkoxylated fatty alcohols, alkyl polyglycosides, soaps, alkyl sulfates, mono- and di-alkyl phosphates, alkyl sulfonates, acyl isethionates, or any combination thereof.

[0394] Suitable vaso-occlusive agents include, for example, petrolatum, mineral oil, beeswax, silicone oil, lanolin and oil-soluble lanolin derivatives, saturated and unsaturated fatty alcohols such as behenyl alcohol, hydrocarbons such as squalane, and various animal and vegetable oils, such as almond oil, peanut oil, wheat germ oil, linseed oil, jojoba oil, apricot kernel oil, walnut, palm nut, pistachio, sesame seed, rapeseed, juniper oil, corn oil, peach kernel oil, poppy seed oil, pine oil, castor oil, soybean oil, avocado oil, safflower oil, coconut oil, hazelnut oil, olive oil, grapeseed oil, and sunflower seed oil.

[0395] Suitable emollients include, for example, dodecane, squalane, cholesterol, isohexadecane, isononyl isononanoate, PPG ethers, petrolatum, lanolin, safflower oil, castor oil, coconut oil, cottonseed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof, and mixtures thereof.

[0396] According to one detailed embodiment of the invention, the composition contains at least one particulate or non-particulate water-soluble or water-insoluble colorant.

[0397] According to a specific embodiment, the colorant is present in a proportion of at least 0.01% by weight relative to the total weight of the composition.

[0398] For purposes of this invention, the term "water-soluble colorant" means any natural or synthetic, generally organic compound that is soluble in an aqueous phase or a water-miscible solvent and that is capable of imparting color.

[0399] Examples of water-soluble dyes may in particular be synthetic or natural water-soluble dyes such as FDC Red No. 4, DC Red No. 6, DC Red No. 22, DC Red No. 28, DC Red No. 30, DC Red No. 33, DC Orange No. 4, DC Yellow No. 5, DC Yellow No. 6, DC Yellow No. 8, FDC Green No. 3, DC Green No. 5, FDC Blue No. 1, betanin (beetroot), carmine, copper chlorophyllin, methylene blue, anthocyanins (enocyanin, black carrot, hibiscus and elderberry), caramel and those made of riboflavin.

[0400] According to specific embodiments, the colorant may be a pigment, a pearlescent agent, and / or a metallic tinted particle.

[0401] The term "pigment" should be understood to mean white or colored inorganic or organic particles insoluble in aqueous solution intended to color and / or opacify the composition containing them.

[0402] The pigments can be white or colored and inorganic and / or organic.

[0403] Inorganic pigments that may be used with particular embodiments of the present invention may be made of titanium oxide, titanium dioxide, zirconium oxide, cerium oxide or cerium dioxide and also zinc oxide, iron oxide or chromium oxide, ferric blue, manganese violet, ultramarine blue and chromium hydrates and mixtures thereof.

[0404] It can also be a pigment with a structure that can be, for example, of the sericite / brown iron oxide / titanium dioxide / silica type. Such pigments are, for example, sold by the Chemicals and Catalysts company under the reference Coverleaf NS or JS, and have a brightness ratio in the region of 30. They can also be pigments with a structure that can be, for example, of the silica microsphere type containing iron oxide. An example of a pigment with such a structure is the product sold by the company Miyoshi under the reference PC Ball PC-LL-100 P, which pigment is composed of silica microspheres containing yellow iron oxide.

[0405] The term "pearlescent agent" is to be understood to mean any shaped pearlescent or non-pearlescent particles that exhibit color effects by optical interference, especially produced by certain mollusks in their shells or alternatively synthesized.

[0406] The pearling agent may be selected from pearl pigments such as titanium dioxide-coated mica, titanium dioxide-coated mica, titanium dioxide-coated mica, titanium dioxide-coated mica, titanium dioxide-coated mica with organic dyes, and also pearl pigments based on bismuth oxychloride. The pearling agent may also be a mica particle having at least two successive metal oxide and / or organic dye layers superimposed on its surface.

[0407] Examples of pearling agents that may also be mentioned include natural mica coated with titanium oxide, iron oxide, natural pigments or bismuth oxychloride.

[0408] Among the commercially available pearlescent agents, mention may be made in particular of the pearlescent agents Timica, Flamenco and Duochrome (mica-based) sold by Engelhard, Timiron pearlescent agent sold by Merck, Prestige mica-based pearlescent agent sold by Eckart and Sunshine synthetic mica-based pearlescent agent sold by Sun Chemical.

[0409] The pearlescent agent may more particularly have a color or shade such as yellow, pink, red, bronze, orange, brown, gold and / or copper.

[0410] According to one detailed embodiment of the invention, the composition contains at least one filler.

[0411] For the purposes of the present invention, the term "filler" is understood to mean colorless or white solid particles of any form that are in an insoluble and dispersed form in the medium of the composition.

[0412] Such fillers, of inorganic or organic, natural or synthetic nature, give softness to the compositions containing them and provide a matt effect and uniformity to the cosmetic result.

[0413] Fillers according to specific embodiments of the present invention may be in lamellar morphology (or platelet morphology), spherical morphology (or globular morphology), fiber morphology, or any other intermediate morphology between these defined morphologies.

[0414] Non-limiting examples of organic spherical fillers include, for example, polyamide powders and in particular Nylon® powders such as nylon-12 or polyamide 12 sold under the trade name ORGASOL by Arkema; ​​polyethylene powders; polytetrafluoroethylene powders (Teflon *microspheres based on acrylic copolymers, such as the copolymer of ethylene glycol dimethacrylate / lauryl methacrylate copolymer sold by Dow Corning under the trade name Polytrap; hollow microspheres and expanded powders, such as those sold by Kemanord Plast under the trade name Expancel or by Matsumoto under the trade name Micropearl F 80 ED; silicone resin microbeads, such as those sold by Toshiba Silicone under the trade name Tospearl; polymethyl methacrylate microspheres, such as those sold by Matsumoto under the trade name Microsphere M-100 or by Wacker under the trade name Covabead LH85; ethylene acrylate copolymer powders, such as those sold by Sumitomo Seika Chemicals under the trade name Flobeads; starch powders, such as those of corn starch, wheat or rice, crosslinked or otherwise, such as those sold by National Powders of natural organic materials, such as starch powder crosslinked with octenyl succinic anhydride, sold under the trade name Dry-FLO by Starch; metal soaps derived from organic carboxylic acids having 8 to 22 carbon atoms, preferably 12 to 18 carbon atoms, such as zinc stearate, magnesium or lithium laurate, zinc magnesium myristate, Polyporus L *200 (Chemdal Corporation), polyurethane powders, in particular crosslinked polyurethane powders containing copolymers containing trimethylolhexyl lactone as a polymer of hexamethylene diisocyanate / trimethylolhexyl lactone, sold by Toshiki under the trade name Plastic Powder D-400 (registered trademark) or Plastic Powder D-800 (registered trademark), carnauba microwaxes such as those sold by Micro Powders under the trade name MicroCare 350 (registered trademark), synthetic microwaxes such as those sold by Micro Powders under the trade name MicroEase 114S (registered trademark), microwaxes consisting of a mixture of carnauba wax and polyethylene waxes such as those sold by Micro Powders under the trade name Micro Care 300 (registered trademark) and 310 (registered trademark), microwaxes consisting of a mixture of carnauba wax and synthetic waxes such as those sold by Micro Powders under the trade name Micro Care 325 (registered trademark), Micropoly and polyethylene microwaxes such as those sold under the trade names 200®, 220®, and 220L® 250S®. Spherical inorganic fillers can include hydrophobic aerogel silica particles.

[0415] Non-limiting examples of layered fillers that may be used with particular embodiments of the present invention include phyllosilicates such as talc, mica, perlite, and mixtures thereof.

[0416] According to a specific embodiment, the composition comprises a dispersant.

[0417] Such dispersants can be, for example, surfactants, oligomers, polymers or mixtures of some of these.

[0418] Depending on the fluidity of the composition that one wishes to achieve, the compositions of the present invention may incorporate one or more thickening or gelling agents.

[0419] Thickening or gelling agents suitable for use in the present invention may be hydrophilic, that is, soluble or dispersible in water.

[0420] Hydrophilic gelling or thickening agents that may be mentioned in particular include water-soluble or water-dispersible thickening polymers.

[0421] Suitable thickening agents include, for example, non-ionic water-soluble polymers such as hydroxyethyl cellulose (commercially available under the trademark Natrosol® 250 or 350), cationic water-soluble polymers such as Polyquat 37 (commercially available under the trademark Synthalen® CN), fatty alcohols, fatty acids and their alkali salts, and mixtures thereof.

[0422] Other non-limiting examples of thickeners are in particular modified or unmodified carboxyvinyl polymers such as the products sold under the trade name Carbopol (CTFA name: Carbomer) by Goodrich; polyacrylates and polymethacrylates such as the products sold under the trade name Lubrajel and Norgel by Guardian or the products sold under the trade name Hispagel by Hispano Chimica; polyacrylamides; optionally crosslinked and / or neutralized 2-acrylamido-2-methylpropanesulfonic acid polymers and copolymers, such as poly(2-acrylamido-2-methylpropanesulfonic acid) (CTFA name: ammonium polyacryloyldimethyltaurate) sold under the trade name Hostacerin AMPS® by Clariant; Sepigel 305 (CTFA name: polyacrylamide / C13-14 isoparaffin / laureth-7) and Simulgel Crosslinked anionic copolymers of acrylamide and AMPS in the form of water-in-oil emulsions, such as those sold under the trade name 600 (CTFA name: Acrylamide / Sodium Acryloyldimethyl Taurate Copolymer / Isohexadecane / Polysorbate 80);Hydrophobically modified polymers of this type include copolymers of the ammonium salt of 2-acrylamido-2-methylpropanesulfonic acid and ethoxylated C12-C14 alkyl methacrylate (non-crosslinked copolymers available from Genapol LA-070 and AMPS) sold by Clariant under the trade name Aristoflex LNC (CTFA name: Ammonium Acryloyldimethyltaurate / Laureth-7 Methacrylate Copolymer) and crosslinked copolymers of the ammonium salt of 2-acrylamido-2-methylpropanesulfonic acid and ethoxylated (25EO) stearyl methacrylate (preferably crosslinked with trimethylolpropane triacrylate and available from Genapol HMS) sold by Clariant under the trade name Aristoflex HMS. T-250 and copolymers available from AMPS® (CTFA name: Ammonium Acryloyldimethyltaurate / Steareth-25 Methacrylate Crosspolymer); polysaccharide biopolymers such as xanthan gum, guar gum, locust bean gum, acacia gum, scleroglucan, chitin and chitosan derivatives, carrageenan, gellan, alginates, celluloses such as microcrystalline cellulose, carboxymethylcellulose, hydroxymethylcellulose, and hydroxypropylcellulose; and mixtures thereof.

[0423] Representative examples of solubilizers that can be used in this regard of the present invention include, without limitation, complex-forming solubilizers such as citric acid, ethylenediaminetetraacetate, sodium metaphosphate, succinic acid, urea, cyclodextrin, polyvinylpyrrolidone, diethylammonium orthobenzoate, and micelle-forming solubilizers such as TWEEN and Spans, e.g., TWEEN 80. Other solubilizers that can be used in the compositions of the present invention are, for example, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene n-alkyl ethers, n-alkylamine N-oxides, poloxamers, organic solvents, phospholipids, and cyclodextrins.

[0424] Suitable permeation enhancers include, but are not limited to, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), allantoin, urasol, N,N-dimethylacetamide (DMA), decylmethyl sulfoxide (C 10 Examples of suitable permeation enhancers include methylcellulose (MSO), polyethylene glycol monolaurate (PEGML), propylene glycol (PG), propylene glycol monolaurate (PGML), glycerol monolaurate (GML), lecithin, 1-substituted azacycloheptan-2-ones, particularly 1-n-dodecylcycloazacycloheptan-2-one (available under the trademark Azone® from Whitby Research Incorporated, Richmond, Virginia), alcohols, and the like. The permeation enhancer can also be a vegetable oil. Such oils include, for example, safflower oil, cottonseed oil, and corn oil.

[0425] Suitable anti-irritants include, for example, steroidal and non-steroidal anti-inflammatory agents or other materials such as aloe vera, chamomile, alpha-bisabolol, cola nitida extract, green tea extract, tea tree oil, licorice extract, allantoin, caffeine or other xanthines, glycyrrhizic acid and its derivatives, and the like.

[0426] Exemplary additional active agents according to some embodiments of the present invention include, without limitation, one or more or any combination of anti-acne agents, anti-aging agents, wrinkle reducing agents, skin lightening agents, sebum reducing agents, anesthetics, anti-itch agents, anti-neoplastic agents, immunomodulators, interferons, antidepressants, antihistamines, vitamins (e.g., A, C, E, B3, B5, K and derivatives thereof, particularly esters thereof), hyaluronic acid, minerals (e.g., Dead Sea minerals), hormones, and anti-dandruff agents.

[0427] Exemplary additional active agents according to some embodiments of the present invention include, without limitation, one or more or any combination of vitamins, minerals (e.g., Dead Sea minerals), ceramides, hyaluronic acid, proteins (e.g., collagen, elastin), hydroxy acids (e.g., alpha or beta hydroxy acids), peptides, amino acids, sunscreens, herbal or botanical extracts, fungi, herbs (e.g., medicinal herbs, seaweed, algae), urea and its hydroxylated derivatives such as N-(2-hydroxyethyl)urea, salicylic acid, sequestrants (e.g., EDTA), and the like.

[0428] According to specific embodiments, the cosmetic composition comprises a compound selected from the group consisting of glycerin, cetearyl alcohol, cetearyl glucoside, caprylic acid, capric triglyceride, isononyl isononanoate, Simmondsia chinensis (jojoba) seed oil, Butyrospermum parkii (shea) butter, Cocos nucifera (coconut) oil, sodium polyacrylate, phenoxyethanol, glycol caprylate, tocopheryl acetate, and fragrance.

[0429] According to specific embodiments, the total amount of bilayer-forming lipids and polymeric compounds is in the range of 0.1 to 10, or 0.1 to 5, or 1 to 10, or 1 to 5 weight percent of the total weight of the composition, including any intermediate values ​​and subranges therebetween.

[0430] According to specific embodiments, the composition is in the form of a gel, and the total amount of bilayer-forming lipids and polymeric compounds is in the range of 1 to 10 or 1 to 5 wt. % of the total weight of the composition, including any intermediate values ​​and subranges therebetween.

[0431] According to specific embodiments, the composition is in the form of a cream or emulsion, and the total amount of bilayer-forming lipids and polymeric compounds is in the range of 0.1 to 5 or 0.1 to 1 wt. % of the total weight of the composition, including any intermediate values ​​and subranges therebetween.

[0432] The formulations as described herein may be or be used to make cosmetic products and may be used in beauty care.

[0433] Exemplary non-limiting products include, but are not limited to, anti-acne products, anti-diaper rash products, shampoos, body lotions, body creams, face creams, face lotions, face masks, body washes and / or face wash products, cleansing products (for hair and / or skin and / or mucosal tissues such as the mouth or vagina), hygiene products, anti-pigmentation products, makeup products, anesthetic products, and sun protection products.

[0434] According to a particular embodiment, the cosmetic composition is used for skin care.

[0435] "Skin care" means regulating and / or improving the condition of the skin. Some non-limiting examples include improving the appearance and / or feel of the skin by providing a smoother and more uniform appearance and / or feel; increasing the thickness of one or more skin layers; improving the elasticity or firmness of the skin; improving the firmness of the skin; and reducing the oily, shiny, and / or dull appearance of the skin, improving the hydration or moisturization of the skin, improving the appearance of fine lines and / or wrinkles, improving skin peeling or scaling, plumping the skin, improving skin barrier properties, improving skin tone, reducing the appearance of redness or skin blemishes, and / or improving the brightness, radiance, or clarity of the skin.

[0436] "Skin care active" means a compound or combination of compounds that, upon application to the skin, confers an acute and / or chronic benefit to the skin or cell types commonly found therein. A skin care active may regulate and / or improve the skin or its associated cells (e.g., may improve skin elasticity; may improve skin hydration; may improve skin condition; and may improve cell metabolism).

[0437] "Skin care formulation" means a formulation that contains a skin care active and that regulates and / or improves the condition of the skin.

[0438] As used herein, "skin care product" refers to a product that includes a skin care composition or formulation. Some non-limiting examples of "skin care products" include skin creams, moisturizers, lotions, and body washes. Other examples are provided below. According to an aspect of some embodiments of the present invention there is provided a skin care product comprising a cosmetic or cosmeceutical composition or formulation as described herein for any corresponding embodiment and any combination thereof.

[0439] Non-limiting exemplary skin care products include products for improving the appearance and / or feel of skin by providing a smoother and more uniform appearance and / or feel; products for increasing the thickness of one or more skin layers; products for improving the elasticity or firmness of the skin; products for improving the firmness of the skin; and products for reducing the oily, shiny, and / or dull appearance of skin, products for improving skin hydration or moisturization, products for improving the appearance of fine lines and / or wrinkles, products for improving skin exfoliation or scaling, products for plumping the skin, products for improving skin barrier properties, products for improving skin tone, products for reducing the appearance of redness or skin blemishes, and products for improving the brightness, radiance, or clarity of the skin. Such products may, for example, be applied to the facial skin, neck, trunk, and / or décolleté.

[0440] The formulations and products as described herein can be used to treat, prevent (protect), or reduce damage to keratinous and / or mucosal tissues of a subject.

[0441] Medical, cosmetic or cosmeceutical conditions that may benefit from topical application of a composition, formulation or product as described herein include, but are not limited to, skin cell damage caused by ultraviolet light, skin aging, skin pigmentation, stress, extreme weather, menopause, xerosis, ichthyosis, keratosis, keratoderma, pruritus, acne, dermatitis, neurodermatitis, dermatitis herpetiformis, actinic keratosis, hyperkeratosis, inflammatory keratosis, eczema, atopic eczema, melanoma, psoriasis, rosacea, urticaria, seborrheic dermatitis, skin cancer, pigmented dry skin, infections caused by pathogenic microorganisms, wounds, inflammation and / or pain, inflammatory diseases or disorders such as tinea pedis (athlete's foot), acne, blackheads (a benign scaly skin condition) and thrombophlebitis, primary Raynaud's phenomenon (PRP), limited cutaneous scleroderma (LCSSc), diabetic ulcer wounds, skin infections, eczema, rashes, immune-mediated systemic diseases, allergic reaction-mediated systemic diseases, viral blisters such as those caused by herpes, anal fissures, anal fissure pain, post-Hirschsprung procedure (for the treatment of obstructive symptoms), acute strangulated internal hemorrhoids, pain and symptoms of chronic elbow extensor tendinopathy (tennis elbow).

[0442] According to some embodiments, the keratinous tissue is facial tissue, hair tissue, or skin tissue (eg, of the décolleté).

[0443] According to some embodiments, the mucosal tissue is vaginal tissue.

[0444] According to some embodiments, the mucosal tissue is in the oral cavity.

[0445] According to some embodiments, the damage is associated with aging.

[0446] According to some embodiments, the damage is a skin condition, e.g., dermatitis and / or conditions associated with conditions such as atopic dermatitis, psoriasis, pigmentation, acne, eczema, xerosis, ichthyosis, keratosis, keratoderma, pruritus, dermatitis, neurodermatitis, dermatitis herpetiformis, actinic keratosis, hyperkeratosis and inflammatory keratoses, atopic eczema, melanoma, rosacea, urticaria, seborrheic dermatitis, skin cancer, and pigmented dry skin.

[0447] According to some embodiments of any composition, formulation, article of manufacture and / or product as described herein, it is packaged in packaging material and is identified by text in or on the packaging material as to its intended use.

[0448] A composition as described herein may be specified for use in the preparation of any of the formulations or products or articles of manufacture as described herein.

[0449] The compositions as described herein may be specified for use in any of the preparations as described herein.

[0450] The products and / or articles of manufacture as described herein may be specified with respect to their intended use as described herein in any corresponding embodiment depending on the formulation that makes up the product or article and depending on other ingredients that may be included in the product.

[0451] According to an additional or alternative aspect of the present invention, there is provided a method of providing cosmetic care to a subject in need thereof, the method comprising applying an effective amount of a cosmetic composition disclosed herein to the skin of the subject, thereby providing the cosmetic care.

[0452] According to a specific embodiment, the subject is a female subject.

[0453] According to a specific embodiment, the subject is an infant (eg, under 4 years of age, under 3 years of age).

[0454] According to specific embodiments, the subject is at least 20 years old, at least 30 years old, at least 40 years old, or at least 50 years old.

[0455] According to a specific embodiment, the subject is an elderly subject. According to specific embodiments, the subject is at least 70 years old or at least 80 years old.

[0456] As used herein, the term "subject" includes mammals of any sex and any age, preferably humans.

[0457] According to a specific embodiment, the subject suffers from dry skin.

[0458] Other definitions: As used herein, the term "hydrocarbon" refers to an organic moiety that contains, as its basic backbone, a chain of carbon atoms substituted primarily with hydrogen atoms. The hydrocarbon can be saturated or unsaturated, can consist of an aliphatic, alicyclic, or aromatic moiety, and can optionally be substituted with one or more substituents (other than hydrogen). The substituted hydrocarbon can have one or more substituents, whereby each substituent can independently be, for example, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, amine, halide, sulfonate, sulfoxide, phosphonate, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, oxo, cyano, nitro, azo, azide, sulfonamide, carboxy, thiocarbamate, urea, thiourea, carbamate, amide, and hydrazine. The hydrocarbon can be a terminal group or a linking group (as these terms are defined herein). The hydrocarbon moiety is optionally interrupted with one or more heteroatoms, including, but not limited to, one or more oxygen, nitrogen, and / or sulfur atoms. In some embodiments of any of the embodiments described herein relating to hydrocarbons, the hydrocarbon is not interrupted by any heteroatoms.

[0459] Preferably, the hydrocarbon moiety has 1 to 20 carbon atoms. Whenever a numerical range is given herein, e.g., "1 to 20," it means that the group (in this case, an alkyl group) can contain 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc. up to and including 20 carbon atoms.

[0460] As used herein, the term "alkyl" refers to any saturated aliphatic hydrocarbon, including straight-chain and branched-chain groups. Preferably, the alkyl group has 1 to 20 carbon atoms. More preferably, the alkyl is a medium-sized alkyl having 1 to 10 carbon atoms. Most preferably, unless otherwise specified, the alkyl is a lower alkyl having 1 to 4 carbon atoms. The alkyl group can be substituted or unsubstituted. When substituted, the substituents can be, for example, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azido, phosphonyl, phosphinyl, oxo, imine, oxime, hydrazone, carbonyl, thiocarbonyl, urea group, thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, as these terms are defined herein.

[0461] As used herein, the term "alkenyl" refers to an unsaturated aliphatic hydrocarbon containing at least one carbon-carbon double bond, including straight-chain and branched-chain groups. Preferably, an alkenyl group has 2 to 20 carbon atoms. More preferably, an alkenyl is a medium-sized alkenyl having 2 to 10 carbon atoms. Most preferably, unless otherwise specified, an alkenyl is a lower alkenyl having 2 to 4 carbon atoms. An alkenyl group can be substituted or unsubstituted. A substituted alkenyl can have one or more substituents, each of which can independently be, for example, alkynyl, cycloalkyl, alkynyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azido, phosphonyl, phosphinyl, oxo, imine, oxime, hydrazone, carbonyl, thiocarbonyl, urea group, thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0462] As used herein, the term "alkynyl" refers to an unsaturated aliphatic hydrocarbon containing at least one carbon-carbon triple bond, including straight-chain and branched-chain groups. Preferably, an alkynyl group has 2 to 20 carbon atoms. More preferably, the alkynyl is a medium-sized alkynyl having 2 to 10 carbon atoms. Most preferably, unless otherwise specified, the alkynyl is a lower alkynyl having 2 to 4 carbon atoms. Alkynyl groups can be substituted or unsubstituted. A substituted alkynyl can have one or more substituents, each of which can independently be, for example, cycloalkyl, alkenyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azido, phosphonyl, phosphinyl, oxo, imine, oxime, hydrazone, carbonyl, thiocarbonyl, urea group, thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0463] The term "alkylene" refers to a saturated or unsaturated aliphatic hydrocarbon linking group, as this term is defined herein, which differs from an alkyl group (when saturated) or an alkenyl or alkynyl group (when unsaturated), as defined herein, only in that the alkylene is a linking group rather than a terminal group.

[0464] A "cycloalkyl" group refers to a saturated or unsaturated all-carbon monocyclic or fused ring (i.e., rings that share adjacent pairs of carbon atoms) group in which one or more of the rings does not have a completely conjugated π-electron system. Examples of cycloalkyl groups include, without limitation, cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexadiene, cycloheptane, cycloheptatriene, and adamantane. Cycloalkyl groups can be substituted or unsubstituted. When substituted, the substituents can be, for example, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azido, phosphonyl, phosphinyl, oxo, imine, oxime, hydrazone, carbonyl, thiocarbonyl, urea, thiourea, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, as these terms are defined herein. When a cycloalkyl group is unsaturated, it can contain at least one carbon-carbon double bond and / or at least one carbon-carbon triple bond. A cycloalkyl group, as this term is defined herein, can be a terminal group where it is attached to a single adjacent atom, or it can be a linking group, as this term is defined herein, that joins two or more moieties.

[0465] An "aryl" group refers to an all-carbon monocyclic or fused-ring polycyclic (i.e., rings that share adjacent pairs of carbon atoms) terminal group having a completely conjugated π-electron system. Examples of aryl groups include, without limitation, phenyl, naphthalenyl, and anthracenyl. Aryl groups can be substituted or unsubstituted. When substituted, the substituent can be, for example, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azido, phosphonyl, phosphinyl, oxo, imine, oxime, hydrazone, carbonyl, thiocarbonyl, urea group, thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, as these terms are defined herein.

[0466] A "heteroaryl" group refers to a monocyclic or fused ring (i.e., rings sharing adjacent pairs of atoms) terminal group having one or more atoms, such as nitrogen, oxygen, and sulfur, in one or more rings, and, in addition, a completely conjugated π-electron system. Examples of heteroaryl groups include, without limitation, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrimidine, quinoline, isoquinoline, and purine. Heteroaryl groups can be substituted or unsubstituted. When substituted, the substituent can be, for example, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azido, phosphonyl, phosphinyl, oxo, imine, oxime, hydrazone, carbonyl, thiocarbonyl, urea group, thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, as these terms are defined herein.

[0467] The term "arylene" refers to a monocyclic or fused polycyclic linking group, as that term is defined herein, and includes linking groups which differ from aryl or heteroaryl groups, as defined herein, only in that the arylene is the linking group rather than the terminal group.

[0468] A "heteroalicyclic" group refers to a monocyclic or fused ring group having one or more atoms, such as nitrogen, oxygen, and sulfur, in one or more rings. These rings may also have one or more double bonds. However, the rings do not have a completely conjugated π-electron system. Heteroalicyclics may be substituted or unsubstituted. When substituted, the substituents can be, for example, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azido, phosphonyl, phosphinyl, oxo, imine, oxime, hydrazone, carbonyl, thiocarbonyl, urea group, thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamido, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, as these terms are defined herein. Representative examples include piperidine, piperazine, tetrahydrofuran, tetrahydropyran, morpholine, and the like. A heteroalicyclic group, as this term is defined herein, can be a terminal group where it is attached to a single adjacent atom, or it can be a linking group, as this term is defined herein, joining two or more moieties.

[0469] As used herein, the terms "amine" and "amino" refer to a group -NR'R'' or -N +refers to any of the R'R"R"' groups, where R', R" and R"' are each hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heteroalicyclic (linked to the amine nitrogen through a ring carbon thereof), aryl, or heteroaryl (linked to the amine nitrogen through a ring carbon thereof), as defined herein. Optionally, R', R" and R'" are hydrogen or alkyl containing 1 to 4 carbon atoms. Optionally, R' and R" (and R'" when present) are hydrogen. When substituted, the carbon atom of the R', R" or R"' hydrocarbon portion that is bonded to the nitrogen atom of the amine is not substituted by oxo (unless expressly indicated otherwise), and thus R', R" and R" are not (for example) carbonyl, C-carboxy, or amido, as these groups are defined herein.

[0470] An "azido" group is -N=N + =N - Refers to the terminal group.

[0471] An "alkoxy" group refers to any of an -O-alkyl, -O-alkenyl, -O-alkynyl, -O-cycloalkyl, and -O-heteroalicyclic end group, as defined herein, or to any of an -O-alkylene, -O-cycloalkyl-, and -O-heteroalicyclic linking group, as defined herein.

[0472] An "aryloxy" group refers to both an --O-aryl and an --O-heteroaryl group, as defined herein, or to an --O-arylene.

[0473] A "hydroxy" group refers to an --OH group.

[0474] A "thiohydroxy" or "thiol" group refers to a --SH group.

[0475] A "thioalkoxy" group refers to any of an -S-alkyl, -S-alkenyl, -S-alkynyl, -S-cycloalkyl, and -S-heteroalicyclic end group, as defined herein, or to an -S-alkylene-, -S-cycloalkyl-, and -S-heteroalicyclic linking group, as defined herein.

[0476] A "thioaryloxy" group refers to both an --S-aryl and an --S-heteroaryl group, as defined herein, or to an --S-arylene.

[0477] A "carbonyl" or "acyl" group refers to either a -C(=O)-R' terminal group, where R' is as defined herein, or to a -C(=O)- linking group.

[0478] A "thiocarbonyl" group refers to either a -C(=S)-R' terminal group, where R' is as defined herein, or to a -C(=S)- linking group.

[0479] A "carboxy," "carboxyl," "carboxyl" or "carboxylate" group refers to both the "C-carboxy" and "O-carboxy" terminal groups as defined herein and to a carboxy linking group as defined herein.

[0480] A "C-carboxy" group refers to a -C(=O)-O-R' group, where R' is as defined herein.

[0481] An "O-carboxy" group refers to an R'C(=O)-O- group, where R' is as defined herein.

[0482] A "carboxy linking group" refers to a -C(=O)-O- linking group.

[0483] An "oxo" group refers to the =O terminal group.

[0484] An "imine" group refers to either a ═N—R′ terminal group, where R′ is as defined herein, or to a ═N-linked group.

[0485] An "oxime" group refers to an =N-OH terminal group.

[0486] A "hydrazone" group refers to either the ═N—NR′R″ terminal group, where each of R′ and R″ is as defined herein, or the ═N—NR′- linking group, where R′ is as defined herein.

[0487] A "halo" group refers to fluorine, chlorine, bromine or iodine.

[0488] A "sulfinyl" group refers to either an -S(=O)-R' terminal group, where R' is as defined herein, or to an -S(=O)- linking group.

[0489] A "sulfonyl" group refers to either an -S(=O)2-R' terminal group, where R' is as defined herein, or to an -S(=O)2- linking group.

[0490] A "sulfonate" group refers to either an -S(=O)2-O-R' terminal group, where R' is as defined herein, or to an -S(=O)2-O- linking group.

[0491] A "sulfate" group refers to either an -OS(=O)2-O-R' terminal group, where R' is as defined herein, or to an -OS(=O)2-O- linking group.

[0492] A "sulfonamide" or "sulfonamido" group includes both S-sulfonamido and N-sulfonamido terminal groups, as defined herein, and sulfonamido linking groups, as defined herein.

[0493] An "S-sulfonamido" group refers to an -S(=O)2-NR'R'' terminal group, where each of R' and R'' is as defined herein.

[0494] An "N-sulfonamido" group refers to an R'S(=O)2-NR''- terminal group, where each of R' and R'' is as defined herein.

[0495] A "sulfonamide linking group" refers to a -S(=O)2-NR'- linking group, where R' is as defined herein.

[0496] A "carbamyl" group includes both O-carbamyl and N-carbamyl end groups, as defined herein, and carbamyl linking groups, as defined herein.

[0497] An "O-carbamyl" group refers to an --O--C(.dbd.O)--NR'R'' terminal group, where each of R' and R'' is as defined herein.

[0498] An "N-carbamyl" group refers to an R'OC(=O)-NR''- terminal group, where each of R' and R'' is as defined herein.

[0499] A "carbamyl linking group" refers to an -OC(=O)-NR'- linking group, where R' is as defined herein.

[0500] "Thiocarbamyl" groups include O-thiocarbamyl, S-thiocarbamyl, and N-thiocarbamyl end groups, as defined herein, and thiocarbamyl linking groups, as defined herein.

[0501] An "O-thiocarbamyl" group refers to an --O-C(.dbd.S)--NR'R'' terminal group, where each of R' and R'' is as defined herein.

[0502] An "N-thiocarbamyl" group refers to an R'OC(=S)NR''- terminal group, where each of R' and R'' is as defined herein.

[0503] An "S-thiocarbamyl" group refers to a -SC(=O)-NR'R'' terminal group, where each of R' and R'' is as defined herein.

[0504] A "thiocarbamyl linking group" refers to an -OC(=S)-NR'- or an -SC(=O)-NR'- linking group, where R' is as defined herein.

[0505] An "amide" or "amido" group includes C-amide and N-amide terminal groups, as defined herein, and amide linking groups, as defined herein.

[0506] A "C-amido" group refers to a -C(=O)-NR'R'' terminal group, where each of R' and R'' is as defined herein.

[0507] An "N-amido" group refers to an R'C(=O)-NR''- terminal group, where each of R' and R'' is as defined herein.

[0508] An "amide linking group" refers to a -C(=O)-NR'- linking group, where R' is as defined herein.

[0509] A "urea group" refers to an -N(R')-C(=O)-NR"R"' terminal group, where each of R', R" and R" is as defined herein, or an -N(R')-C(=O)-NR"- linking group, where each of R' and R" is as defined herein.

[0510] A "thiourea group" refers to an -N(R')-C(=S)-NR"R"' terminal group, where each of R', R" and R" is as defined herein, or an -N(R')-C(=S)-NR"- linking group, where each of R' and R" is as defined herein.

[0511] A "nitro" group refers to a -NO2 group.

[0512] A "cyano" group refers to a -C≡N group.

[0513] The term "phosphonyl" or "phosphonate" refers to a -P(=O)(OR')(OR'') group, where R' and R'' are as defined herein, or a -P(=O)(OR')-O- linking group, where R' is as defined herein.

[0514] The term "phosphate" refers to either an -OP(=O)(OR')(OR'') terminal group, where each of R' and R'' is as defined herein, or an -OP(=O)(OR')-O- linking group, where R' is as defined herein.

[0515] The term "phosphinyl" refers to a -PR'R'' terminal group, where each of R' and R'' is as defined herein, or a -PR'- linking group, where R' is as defined herein.

[0516] The term "hydrazine" refers to either an -NR'-NR''R''' terminal group, where R', R'' and R''' are as defined herein, or an -NR'-NR''- linking group, where R' and R'' are as defined herein.

[0517] The term "hydrazide," as used herein, refers to a -C(=O)-NR'-NR"R"' terminal group, where R', R" and R'" are as defined herein, or to a -C(=O)-NR'-NR"- linking group, where R' and R" are as defined herein.

[0518] The term "thiohydrazide," as used herein, refers to a -C(=S)-NR'-NR''R''' terminal group, where R', R'' and R'''' are as defined herein, or to a -C(=S)-NR'-NR''- linking group, where R' and R'' are as defined herein.

[0519] A "guanidinyl" group refers to either the -RaNC(=NRd)-NRbRc terminal group, where each of Ra, Rb, Rc, and Rd can be as defined herein for R' and R'', or the -R'NC(=NR'')-NR'''- linking group, where R', R'' and R''' are as defined herein.

[0520] A "guanyl" or "guanine" group refers to either the R'"R"NC(=NR')- terminal group, where R', R" and R'", are as defined herein, or to the -R"NC(=NR')- linking group, where R' and R" are as defined herein.

[0521] For any of the embodiments described herein, the compounds described herein can be in the form of a salt, for example a pharmaceutically acceptable salt.

[0522] As used herein, the phrase "pharmaceutically acceptable salt" refers to a charged species of a parent compound and its counterion that is typically used to modify the solubility characteristics of the parent compound and / or reduce any significant irritation to an organism by the parent compound without destroying the biological activity and properties of the administered compound. Pharmaceutically acceptable salts of compounds as described herein may alternatively be formed during the synthesis of the compound, for example, during the isolation of the compound from a reaction mixture or during the recrystallization of the compound.

[0523] In connection with some of the present embodiments, pharmaceutically acceptable salts of the compounds described herein can optionally be acid addition salts and / or base addition salts.

[0524] Acid addition salts comprise at least one basic (e.g., amine and / or guanidinyl) group of a compound in positively charged form (e.g., in which case the basic group is protonated) in combination with at least one counterion derived from the acid of choice to form a pharmaceutically acceptable salt. Thus, an acid addition salt of a compound described herein can be a complex formed between one or more basic groups of the compound and one or more equivalents of the acid.

[0525] A base addition salt comprises at least one acid (e.g., carboxylic acid) group of a compound in negatively charged form (e.g., in this case, the acid group is deprotonated), in combination with at least one counterion derived from a selected base to form a pharmaceutically acceptable salt. Thus, a base addition salt of a compound described herein can be a complex formed between one or more acid groups of a compound and one or more equivalents of a base.

[0526] Depending on the stoichiometric ratio between the charged group(s) of the compound and the counterion of the salt, acid and / or base addition salts can be either simple or polyaddition salts.

[0527] As used herein, the phrase "single addition salt" refers to a salt in which the stoichiometric ratio between the counterion and the charged form of the compound is 1:1, such that the addition salt contains one molar equivalent of counterion per one molar equivalent of compound.

[0528] As used herein, the phrase "polyaddition salt" refers to a salt in which the stoichiometric ratio between counterion and charged form of compound is greater than 1:1, e.g., 2:1, 3:1, 4:1, etc., such that the addition salt contains two or more molar equivalents of counterion per molar equivalent of compound.

[0529] Examples of pharmaceutically acceptable salts would be, without limitation, ammonium or guanidinium cations and their acid addition salts and / or carboxylate anions and their base addition salts.

[0530] Base addition salts can include cationic counterions such as sodium, potassium, ammonium, calcium, magnesium, and the like, which form pharmaceutically acceptable salts.

[0531] Acid addition salts may include, but are not limited to, various organic and inorganic acids such as hydrochloric acid, which results in hydrochloric acid addition salts, hydrobromic acid, which results in hydrobromide acid addition salts, acetic acid, which results in acetic acid addition salts, ascorbic acid, which results in ascorbic acid addition salts, benzenesulfonic acid, which results in besylate addition salts, camphorsulfonic acid, which results in camphorsulfonic acid addition salts, citric acid, which results in citrate addition salts, maleic acid, which results in maleic acid addition salts, malic acid, which results in malic acid addition salts, methanesulfonic acid, which results in methanesulfonic acid (mesylate) addition salts, naphthalenesulfonic acid, which results in naphthalenesulfonic acid addition salts, oxalic acid, which results in oxalic acid addition salts, phosphoric acid, which results in phosphoric acid addition salts, toluenesulfonic acid, which results in p-toluenesulfonic acid addition salts, succinic acid, which results in succinic acid addition salts, sulfuric acid, which results in sulfuric acid addition salts, tartaric acid, which results in tartaric acid addition salts, and trifluoroacetic acid, which results in trifluoroacetic acid addition salts. Each of these acid addition salts may be either a simple or a polyaddition salt, as that term is defined herein.

[0532] Additionally, each of the compounds described herein, including salts thereof, may be in the form of its solvates or hydrates.

[0533] The term "solvate" refers to a complex of variable stoichiometry (e.g., di-, tri-, tetra-, penta-, hexa-, etc.) formed by a solute (a heterocyclic compound described herein) and a solvent that does not interfere with the intended activity of the solute.

[0534] The term "hydrate" refers to a solvate as defined above wherein the solvent is water.

[0535] The compounds described herein may be available as polymorphs, and the present embodiments further encompass any isomorphs of the compounds and any combinations thereof.

[0536] The compounds and structures described herein encompass any stereoisomers, including enantiomers and diastereomers of the compounds described herein, unless a particular stereoisomer is specifically indicated.

[0537] As used herein, the term "enantiomer" refers to a stereoisomer of a compound that is superimposable on its counterpart only by complete inversion / reflection (mirror image) of each other. Enantiomers are said to have "handedness" because they refer to each other like right and left hands. Enantiomers have identical chemical and physical properties except when present in an environment that itself has a handedness, such as any living system. In the context of this embodiment, a compound may exhibit one or more chiral centers, each of which may exhibit the (R) or (S) configuration, and any combination, such that compounds according to some embodiments of the present invention may have any of their chiral centers exhibiting the (R) or (S) configuration.

[0538] As used herein, the term "diastereomer" refers to stereoisomers that are not enantiomers of each other. Diastereoisomerism occurs when two or more stereoisomers of a compound have different configurations at one or more, but not all, equivalent (related) stereocenters and are not mirror images of each other. When only one stereocenter differs from each other for two diastereoisomers, they are epimers. Each stereocenter (chiral center) gives rise to two different configurations, thus giving rise to two different stereoisomers. In the context of the present invention, embodiments of the present invention encompass compounds with multiple chiral centers that give rise to any combination of configurations, i.e., any diastereomers.

[0539] As used herein, the term "about" refers to ±10% and optionally ±5%.

[0540] The terms "include," "including," "includes," "including," "having," and their conjugations mean "including, but not limited to."

[0541] The term "consisting of" means "including and limited to."

[0542] The term "consisting essentially of" means that a composition, method, or structure may include additional components, steps, and / or moieties, but only if the additional components, steps, and / or moieties do not materially alter the basic and novel characteristics of the claimed composition, method, or structure.

[0543] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" can include multiple compounds, including mixtures thereof.

[0544] Throughout this application, various embodiments of the present invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values ​​within that range. For example, the description of a range such as 1 to 6 should be considered to have specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numerical values ​​within that range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the broadness of the range.

[0545] Whenever a range of values ​​is given herein, it is meant to include any recited number (fractional or integer) within the range given. As used herein, the phrases "ranging from / ranging to" a first indicated value and a second indicated value and "ranging from / ranging from" a first indicated value to a second indicated value are used interchangeably and are meant to include the first and second indicated values ​​and all fractional and integer values ​​therebetween.

[0546] As used herein, the term "method" refers to any manner, means, technique or procedure for accomplishing a given task, including but not limited to, any manner, means, technique or procedure known to or readily developed from known manner, means, techniques or procedures to practitioners of chemistry, pharmacology, biology, biochemistry and medicine.

[0547] As used herein, the term "treating" includes inhibiting, substantially arresting, slowing or reversing the progression of a condition, substantially ameliorating the clinical or cosmetic symptoms of a condition, or substantially preventing the appearance of clinical or cosmetic symptoms of a condition.

[0548] It will be understood that certain features of the invention that are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination, or as suitable in any other embodiment described in the present invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperable without those elements.

[0549] The various embodiments and aspects of the present invention as delineated above and claimed in the claims section below find experimental confirmation in the following examples. [Example]

[0550] Reference is now made to the following examples which, together with the above description, illustrate, by way of non-limiting example, some embodiments of the present invention.

[0551] Materials and Experimental Methods Exemplary bilayer-forming lipids, distearoylphosphatidylethanolamine (DSPE) and dipalmitoylphosphatidylethanolamine (DPPE), were obtained from Lipoid.

[0552] An exemplary bilayer-forming lipid, hydrogenated soybean phosphatidylcholine (HSPC), was obtained from Lipoid GmbH.

[0553] An exemplary bilayer-forming lipid, PC S 100 (phosphatidylcholine from soybean), was obtained from Lipoid GmbH.

[0554] MLVs are multilamellar vesicles (liposomes) comprising phospholipids or phospholipids and LPC as described herein in any corresponding embodiment.

[0555] Carbomer, a carbopol-based gel, was obtained from Lubrizol advanced materials Europe BV, catalogue number CBP1058.

[0556] HA, ie, hyaluronic acid, was obtained from "Contipro as": Catalog Numbers: 814-10-01 and 814-12-01.

[0557] Particle size was determined by dynamic light scattering (DLS) measurements using a Zetasizer Nano instrument from Malvern Panalytical. Liposome samples were diluted 10-fold in PBS to a final volume of 1 mL, transferred to a plastic cuvette, equilibrated to 25°C, and subsequently measured in triplicate. The mean Z-average diameter and polydispersity index (PDI) values ​​were reported along with their standard deviations.

[0558] Z-averages were determined using a Malvern Panalytical Zetasizer Nano instrument. Samples were diluted 100-200 times with water to a final volume of 800 μL, transferred to disposable bent-capillary cuvettes, equilibrated to 25 °C, and subsequently measured in triplicate. Z-averages (mean values) and their standard deviations are reported.

[0559] HPLC measurements were performed using an Agilent 1100 system equipped with an evaporative light scattering (ELS) detector using a reversed-phase C8 column (Kinetex C8, 150 × 4.6 mm, 5 μm, 100 A) equilibrated at 30 °C.

[0560] GPC measurements were carried out using an Agilent 1100 system equipped with a refractive index detector using a PFG column combination (PFG column guard + 100 Å PFG single pore + 300 Å PFG single pore) equilibrated at 40 °C.

[0561] Other methods are described below.

[0562] Example 1 Lipid polymer conjugates (LPC) and liposome preparations containing the same Lipid polymer conjugates (LPC): Lipid polymer conjugates (LPCs) are generally prepared as described in U.S. Provisional Patent Application No. 63 / 402,097 and / or the present assignee's concurrently filed PCT International Patent Application with Attorney Docket No. 97558, which claims benefit of priority to U.S. Provisional Patent Application No. 63 / 402,097, all of which are expressly incorporated by reference herein.

[0563] According to some of the optional embodiments described herein, the method for preparing an LPC according to this embodiment comprises reacting an initiator compound having formula V with -[YLZ] n -[Y] m - contacting a plurality of monomers that form a polymer backbone (wherein Y, L, Z, n, and m are as described herein for Formula I) under conditions that promote atom transfer radical polymerization (ATRP), preferably under conditions that promote ARGET-ATRP. [ka] (In the formula, F1, F2, F3, F4, J, K, M, and Q are as defined for formula IV; Ri is an electron transfer functional group.

[0564] According to some of the embodiments described herein, R can be any functional group suitable for electron transfer radical polymerization, typically a group capable of forming a stable radical by itself. Exemplary such groups include halogen (halo), preferably chloro or bromo, more preferably bromo, although any other suitable group is also contemplated.

[0565] As used herein, the term "stable radical" includes any chemical species that contains an unpaired electron in its molecular or atomic structure, but that is relatively long-lived and less reactive than a typical radical. Typically, a stable radical is one that has the ability to energetically stabilize the unpaired electron.

[0566] Conditions that promote ATRP include any conditions known in the art, typically in the presence of a radical-forming reagent such as CuX' or CuX'2 (where X' is typically a halogen) and a suitable ligand.

[0567] According to some of the embodiments described herein, the method is accomplished under conditions that promote ARGET-ATRP. Exemplary such conditions include any known in the art, typically in the presence of CuX' (where X' is typically a halogen), a suitable ligand, and a reducing agent. Examples of safe, inexpensive, commercially available reducing agents that can be used for ARGET-ATRP include, without limitation, ascorbic acid (vitamin C), sodium ascorbate (NaAsc), calcium ascorbate (CaAsc), and hydrazine (dissolved in monohydrate or ethanol), tin 2-ethylhexanoate (tin-2EH), and glucose. For the polymerization of MPC, both CuBr and CuCl (preferably anhydrous) work well with TPMA as an exemplary ligand, while routine catalytic reduction is performed using ascorbic acid (see, e.g., Adler et al., Biomaterials Science, 2021, 9, 5854-5867). Other ligands are also contemplated, including, for example, N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN, CAS No. 16858-02-9).

[0568] Suitable solvents for carrying out the ATRP or ARGET-ATRP process include, without limitation, polar solvents such as alcohols (eg, methanol and / or ethanol).

[0569] According to some of the embodiments described herein, the method is accomplished at a temperature within the range of 10° C. to 50° C., or 15° C. to 50° C., or 15° C. to 30° C., including any intermediate values ​​and subranges therebetween. In some of the embodiments described herein, the method is accomplished at room temperature (i.e., ambient temperature, about 20° C. to about 25° C.).

[0570] According to some of the optional embodiments described herein, contacting the initiator compound with the plurality of monomers is accomplished for a period of from about 1 to about 48 hours, or from about 3 to about 48 hours, or from about 3 to about 36 hours, or from about 3 to about 24 hours, from about 4 to about 48 hours, or from about 4 to about 36 hours, or from about 4 to about 24 hours, from about 6 to about 48 hours, or from about 6 to about 36 hours, or from about 6 to about 24 hours (including any intermediate values ​​and subranges therebetween).

[0571] Exemplary procedures for carrying out the ATRP and ARGET-ATRP methods are described below, and can be manipulated as needed by selecting the initiator compound, the molar ratio of monomers to initiator, manipulating the catalyst solution, ligand and / or reduction, and selecting the synthesis protocol as exemplified for Procedures 2 and 3.

[0572] According to some of the optional embodiments described herein, the method is accomplished by contacting a catalyst solution containing a catalyst and a ligand with a solution containing an initiator compound, preferably under an inert atmosphere (e.g., argon), and a solution of multiple monomers in a molar ratio to the initiator compound selected to provide the desired length (number of repeating backbone units) for the resulting LPC.

[0573] According to some of the optional embodiments described herein, the molar ratio of catalyst to initiator is about 1:1.

[0574] According to some of the optional embodiments described herein, the method is accomplished by ARGET-ATRP using procedures known in the art. In some of these embodiments, a catalyst solution is prepared by dissolving a catalyst and a ligand in a polar solvent (e.g., an alcoholic solvent such as MeOH or EtOH, preferably EtOH). In an exemplary procedure (e.g., Procedure 2), the catalyst solution is added to a mixture of an initiator compound, a reducing agent, and multiple monomers in a polar solvent (e.g., an alcoholic solvent) as described herein. In another exemplary procedure (e.g., Procedure 3), the catalyst solution is added to a mixture of an initiator compound and multiple monomers in a polar solvent (e.g., an alcoholic solvent) as described herein, followed by the addition of a reducing agent.

[0575] In some of the embodiments described herein, the molar ratio of the monomer(s) as described in any corresponding embodiment and any combination thereof to the initiator compound as described herein is in the range of 5:1 to 200:1, or 10:1 to 150:1, or 20:1 to 100:1, or 30:1 to 75:1, including any intermediate values ​​and subranges therebetween, which determines the number of repeat units in the resulting polymeric compound (LPC).

[0576] In some embodiments, a molar ratio of 50:1 or less (e.g., about 30:1 or about 25:1) provides a short-chain LPC as described herein in corresponding embodiments, comprising fewer than 100 or fewer than 80 repeat units (as indicated by the variable n in Formula I as described herein) in the polymer portion.

[0577] In some embodiments, a molar ratio of 60:1 or greater (e.g., from about 60:1 to about 80:1) provides a longer chain LPC, as described herein in corresponding embodiments, comprising at least 80 repeat units (e.g., 80 to 120) in the polymer portion (as indicated by the variable n in Formula I as described herein).

[0578] According to some of the optional embodiments described herein, the method further comprises isolating the polymeric compound.

[0579] Isolation of the resulting polymeric compound (e.g., a polymeric compound having Formula I as described herein for any corresponding embodiment and any combination thereof) can be achieved by any work-up method known in the art, preferably in connection with ATRP methods, including, for example, TFF, column chromatography, and / or precipitation. Exemplary such procedures are described below.

[0580] According to some of the optional embodiments described herein, isolation of the macromolecular compound does not involve acidification, i.e., exposing the macromolecular compound to an acidic environment.

[0581] According to some of the optional embodiments described herein, isolation of the polymeric compound is carried out by precipitation, i.e., by precipitating the polymeric compound from the polymerization reaction mixture, for example, by contacting the mixture with an antisolvent in which the polymeric compound is insoluble, in a ratio of antisolvent:reaction mixture ranging from 2:1 to 50:1, including any intermediate values ​​and subranges therebetween.

[0582] Exemplary anti-solvents include, but are not limited to, ketones such as acetone, dimethoxyethane (DME), chloroform (CHCl), dichloromethane (DCM), tetrachloroethylene (CCl), dimethyl carbonate (DMC), diethyl carbonate (DEC), and methyl tert-butyl ether (MTBE). In an exemplary embodiment, the anti-solvent is a ketone, e.g., acetone.

[0583] According to some of the optional embodiments described herein, isolating the macromolecular compound further comprises column chromatography before and / or after precipitation.

[0584] As an exemplary LPC, DPPE-Ph-pMPC was used, characterized by various values ​​of n, as indicated below.

[0585] The chemical structure and an exemplary general synthetic protocol (Procedure 2) used to prepare this exemplary LPC are illustrated in FIG.

[0586] Preparation of DPPE-Ph-Br initiator (atom transfer radical polymerization (ATRP) initiator): In an exemplary procedure, DPPE-Ph-Br was prepared by a two-step reaction as follows: (a) Stöcklich esterification of DL-α-bromophenylacetic acid with 4-nitrophenol to give the activated 4-nitrophenol ester (4NP-OC-CHPhBr), and (b) reaction of the resulting ester with DPPE to give DPPE-Ph-Br, as illustrated in Figure 1. The resulting ester can be reacted with other glycerophospholipids to provide additional Ph-Br-based initiators.

[0587] (a) Synthesis of 4-nitrophenyl 2-bromo-2-phenylacetate (4NP-OC-CHPhBr): DL-α-bromophenylacetic acid (4.30 grams, 20 mmol, 1.0 molar equivalent), 4-nitrophenol (3.06 grams, 22 mmol, 1.1 molar equivalent), and 4-DMAP (0.244 grams, 2 mmol, 0.1 molar equivalent) were weighed into a round-bottom flask equipped with a magnetic stir bar. THF (20 mL per gram of DL-α-bromophenylacetic acid) was added to the flask, and stirring was continued until all solids were completely dissolved. The flask was then sealed and cooled to approximately 5°C using an ice bath, and dicyclohexylcarbodiimide (DCC, 4.54 grams, 22 mmol, 1.1 molar equivalent) was added. After stirring for 10 minutes, the ice bath was removed, and the flask was allowed to reach room temperature. The reaction mixture was allowed to stir at ambient temperature for an additional 3 hours, and then its contents were filtered by gravity using plain filter paper into an evaporation flask. The reaction flask and filtered urea by-product were washed twice with DCM (25 mL), and the combined filtrates were evaporated to dryness using a rotary evaporator. The resulting crude yellowish oily mixture was redissolved in DCM (10-15 mL) and loaded onto a silica column eluted with DCM. The collected fractions containing the product (identified by TLC with UV light at 254 nm, eluent = DCM, Rf = 0.95) were combined, evaporated to dryness, and placed under high vacuum overnight. The product was obtained as a clear, slightly yellowish oil, which crystallized after drying under high vacuum overnight to give 5.05 grams of a pale yellow solid in 75% yield.

[0588] (b) Synthesis of 2,3-bis(palmitoyloxy)propyl(2-(2-bromo-2-phenylacetamido)ethyl)phosphate (DPPE-Ph-Br ATRP initiator): 4NP-OC-CHPhBr (5.05 grams, 15.0 mmol, 1.2 molar equivalents) was dissolved in DCM (15 mL per gram of 4NP-OC-CHPhBr) in a round-bottom flask equipped with a magnetic stir bar. DPPE (8.66 grams, 12.5 mmol, 1.0 molar equivalents) was then added to the flask, followed by a rinse with additional DCM (10 mL per gram of DPPE). TEA (4.2 mL, 30.0 mmol, 2.4 molar equivalents) was added, and the flask was heated to 50 °C using a water bath, resulting in a gentle solvent reflux. At the beginning of the reaction, bubbles appeared in the solution, which disappeared after 1 hour of reflux and vigorous stirring. The reaction was refluxed for an additional 2 hours and then allowed to cool to room temperature. The contents of the flask were transferred to a separatory funnel, and the organic phase was washed three times, each time with an equal volume of 1 molar (M) HCl. The combined aqueous acidic phase was extracted twice with DCM (50 mL). The combined organic DCM phase was dried over anhydrous Na2SO4, filtered, and evaporated to 30–50 mL. The DPPE-Ph-Br product was precipitated by adding the concentrated DCM solution to a laboratory bottle filled with stirred MeOH (75 mL per gram of DPPE) and placing the bottle in a refrigerator for at least 2 hours. The precipitated product was collected by filtration, washed twice with cold MeOH (50 mL), and dried while still applying suction for at least 10 minutes. Finally, the precipitate was dried under high vacuum overnight to give 9.82 grams of DPPE-Ph-Br in 88% yield.

[0589] In another exemplary procedure, DPPE-Ph-Br was prepared as follows.

[0590] (a) Activation of αBPA with NHS for coupling reaction with DPPE: DL-α-bromophenylacetic acid (αBPA, 7.53 grams, 35.0 mmol, 1.4 molar equivalents relative to DPPE) and N-hydroxysuccinimide (NHS, 4.32 grams, 37.5 mmol, 1.5 molar equivalents relative to DPPE) were added to a 100 mL round-bottom flask equipped with a magnetic stirrer and a powder funnel. Tetrahydrofuran (THF, 40 mL) was added through the powder funnel, and stirring was continued until both solids were completely dissolved. Diisopropylcarbodiimide (DIC, 5.1 mL, 32.5 mmol, 1.3 molar equivalents relative to DPPE) was then added to the flask using a syringe, the flask was sealed, and the reaction was allowed to stir at room temperature for 1 hour. The precipitated DIC-urea by-product was then collected by gravity filtration using standard filter paper, and the reaction flask and filter paper were washed with 5 mL of THF. The resulting clear solution was saved for the next step.

[0591] (b) Reaction of DPPE with NHS ester of αBPA: In parallel, a 500 mL round-bottom flask was equipped with a magnetic stirrer and a powder funnel. 1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE, 17.3 g, 25 mmol) was added to the flask, followed by chloroform (CHCl3, 175 mL) via the powder funnel. Next, triethylamine (TEA, 3.8 mL, 27.5 mmol, 1.1 molar equivalents relative to DPPE) was added to the flask using a syringe, and the contents of the flask were vigorously stirred while the flask was heated to 70 °C. After complete dissolution was achieved, the flask was gradually cooled to 35 °C. The clear NHS ester solution from step (a) was then added all at once, and the reaction was allowed to proceed at 35 °C for 1 h. The flask was then allowed to cool to room temperature, the CHCl3 was evaporated under reduced pressure, and the resulting oily residue was transferred to a 1 L separatory funnel using a total of 500 mL of ethyl acetate (EtOAc). The organic phase in the separatory funnel was washed three times with 1M HCl (250 mL), three times with brine (250 mL), dried over anhydrous MgSO4, and filtered by gravity using standard filter paper into a 1 L laboratory bottle to separate any solid particles. The laboratory bottle containing the clear EtOAc solution was placed in a -20 °C freezer for 2 h, during which time the DPPE-Ph-Br product precipitated as a white solid. DPPE-Ph-Br was filtered off using a Buchner filtration system, and the collected product was washed twice with cold EtOAc (25 mL). The product was dried under high vacuum to constant weight. Yields of 80–90% of pure DPPE-Ph-Br were achieved.

[0592] Since the above procedure involves in situ activation of αBPA and does not require any purification of the active ester, DPPE-Ph-Br can instead be prepared in a one-pot reaction. Activation is carried out by converting αBPA to its active NHS ester using diisopropylcarbodiimide (DIC) as a coupling reagent.

[0593] Synthesis of DPPE-Ph-pMPC via ARGET-ATRP: DPPE-Ph-pMPC was obtained by polymerizing MPC from an exemplary DPPE-Ph-Br initiator via ARGET-ATRP using anhydrous CuCl as the catalyst, tris(2-pyridylmethyl) (TPMA) as the ligand, and ascorbic acid or sodium ascorbate (NaAsc) as the reducing agent (see, e.g., Figure 1).

[0594] Generally, the catalyst, reducing agent, and ligand and their solutions can alternatively be replaced by others known in the art for ARGET-ATRP. The initiator can also be replaced by any initiator corresponding to the desired LPC as described herein (see, for example, Formula V).

[0595] Generally, the amount of ligand is about 2 molar equivalents relative to the CuCl catalyst, the amount of reducing agent is about 10 molar equivalents relative to the CuCl catalyst, the amount of DPPE-Ph-Br is about 1 molar equivalent relative to the CuCl catalyst, and the amount of MPC is predetermined based on the desired number of repeat units (n). The length of the LPC is determined by the molar ratio of DPPE-Ph-Br to MPC, and the amount of MPC added to the reaction was selected accordingly. For example, a 1:25 molar ratio of DPPE-Ph-Br:MPC resulted in an LPC containing about 50-80 or 50-60 repeat units. A 1:50 or 1:60 molar ratio resulted in an LPC containing about 80-120 or 110-120 repeat units.

[0596] In all synthetic protocols described herein for the preparation of lipid-polymer conjugates, the type of lipid moiety can be manipulated by tailoring each initiator (which contains a lipid moiety of choice). Furthermore, the length of the polymer moiety (e.g., the number of repeating units of an MPC) is controlled by the molar equivalent of a selected monomer (e.g., an MPC) relative to the initiator (the molar ratio of monomer to initiator).

[0597] The following exemplary general procedure was used, using the following catalyst solution: CuX2 (X = Cl or Br, 0.10 molar equivalents relative to initiator) was dissolved in an alcohol solvent (e.g., MeOH or EtOH, preferably EtOH), TPMA (0.20 molar equivalents relative to initiator) was added to the green solution of CuCl2, and the resulting metal-ligand complex solution was mixed for at least 15 minutes.

[0598] In one exemplary procedure (also referred to herein as Procedure 2), initiator (1 molar equivalent) and ascorbic acid (1.41 molar equivalents relative to initiator) were added to an oven-dried round-bottom Schlenk flask equipped with a magnetic stir bar, followed by a solution of MPC (25-100 molar equivalents relative to initiator, e.g., 30 molar equivalents relative to initiator) in a selected solvent (e.g., EtOH). The total volume of solvent (e.g., EtOH) used in the reaction was set according to the amount of MPC to achieve a 15% w / v concentration. The catalyst solution was then added to the Schlenk flask, the flask was sealed with a rubber septum, and the contents were mixed together to form a clear, greenish solution.

[0599] In an alternative procedure (also referred to herein as Procedure 3), initiator (1 molar equivalent) was added to an oven-dried round-bottom Schlenk flask equipped with a magnetic stir bar, as described above, followed by a solution of MPC (25-100 molar equivalents relative to initiator, e.g., 30 molar equivalents relative to initiator) in a solvent of choice (e.g., EtOH), followed by the catalyst solution. The flask was sealed with a rubber septum, and the contents were mixed together until a clear, greenish solution formed, and all solids were completely dissolved before sodium ascorbate (1.00 molar equivalents relative to initiator) was added.

[0600] Once all components were introduced into the flask, the oxygen present therein was purged by bubbling argon gas through the solution for 30 minutes, after which the Schlenk valve was tightly closed and the polymerization mixture was allowed to stir at ambient temperature for 2-24 (e.g., 5-6) hours.

[0601] In both Procedures 2 and 3, the polymerization was quenched by opening the flask to admit air. The resulting solution was optionally filtered using a Buchner funnel equipped with Whatman paper. The resulting solution (or filtrate) was added dropwise to acetone with stirring to precipitate the polymer product as a white solid. The volume of acetone was adjusted to 10 times the volume of the alcohol solvent (e.g., EtOH). The formed slurry was allowed to stir vigorously for an additional 30 minutes, after which the precipitate was filtered through a glass funnel, and the precipitation vessel and polymer were washed three times with acetone. The resulting polymer (LPC) exhibited a paste-like texture and was purified by dissolving it in EtOH and / or deionized water (15 mL per gram of LPC), optionally removing impurities by filtration. When EtOH was used, the solvent was evaporated, and the residue was dissolved in purified water, filtered from insoluble impurities, and further purified by TFF (8–10 diafiltrations with deionized water). When water was used, the resulting aqueous solution was filtered from insoluble impurities and then further purified using TFF (8-10 diafiltrations with DIW). The aqueous LPC solution was placed in a -80°C freezer for at least 2 hours and then lyophilized for at least 48 hours (e.g., 96 hours).

[0602] The number of units in the resulting LPC was determined based on the Mw of the product as determined by GPC analysis.

[0603] All of the LPCs tested were prepared according to Procedure 2 as described herein using DPPE-Ph-Br as the initiator compound.

[0604] IM22-1053 was prepared as described above using 30 molar equivalents of MPC relative to DPPE-Ph-Br.

[0605] IM22-1054 was prepared as described above using 80 molar equivalents of MPC relative to DPPE-Ph-Br.

[0606] IM22-1055 was prepared as described above using 30 molar equivalents of MPC relative to DPPE-Ph-Br.

[0607] IM22-1056 was prepared as described above using 30 molar equivalents of MPC relative to DPPE-Ph-Br.

[0608] IM22-1063 was prepared as described above using 25 molar equivalents of MPC relative to DPPE-Ph-Br.

[0609] Table 1 below presents the characterizing properties of the obtained LPCs.

[0610] [Table 1]

[0611] Liposomes formed with DPPE-Ph-pMPC of various lengths and dipalmitoylphosphatidylcholine lipid (DMPC), hydrogenated soybean phosphatidylcholine (HSPC), and soybean-derived phosphatidylcholine (PC S 100) as phospholipids were prepared and added to various cosmetic formulations as described in Example 2 below.

[0612] Liposome stock solutions were generally prepared as follows: The protocol for each formulation is described in further detail in Example 2 below.

[0613] Dissolving lipids in ethanol: 55 grams of ethanol AR was added to a 250 ml flask and heated to a temperature ranging from 30 to 70°C. The LPC of choice was weighed and added to the flask, followed by the phospholipid of choice. A reference liposome formulation was prepared without LPC. A 2.5 cm oval magnet was added to the flask, and the ingredients were mixed at a temperature ranging from 30 to 70°C until a homogeneous, clear solution was obtained (typically about 20 minutes).

[0614] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 35°C, -2 tilt, 250 RPM) followed by a second verification evaporation for 15 minutes, resulting in the formation of a dry lipid cake.

[0615] Water Hydration: 55 grams of deionized water was added to a dry flask along with a 2.5 cm magnet, and the flask was stirred for 20-70 minutes at a holding temperature ranging from 30-70°C.

[0616] Homogenization: The solution was placed in a 250 ml laboratory bottle immersed in a 35°C bath and homogenized at 7-9K RPM for 30-60 minutes.

[0617] Table 2 below lists the preparation parameters and characterizing properties of exemplary liposomal formulations.

[0618] [Table 2]

[0619] Example 2 Cosmetic gel formulations The common ingredient for all formulations was carbomer gel. To prepare the gel, a pre-made gel stock (1.5% Carbopol® content) was prepared generally as follows: 15 grams of Carbopol® 990 was added to deionized water (930 grams) at room temperature and homogenized at 9K RPM for 7 minutes, followed by the addition of preservative (40 grams of "ISCAGARD OP") and mixing for 1 minute. 15 grams of triethanolamine was then added to neutralize the acidic carbomer.

[0620] For gels containing a common humectant such as glycerin, 37.5 grams of stock gel was mixed with 9.4 grams of glycerin and 140.8 grams of deionized water using an overhead stirrer equipped with a 6 cm wide stainless steel "anchor" type stir bar.

[0621] Samples containing multilamellar vesicles composed of either phospholipids (e.g., dipalmitoylphosphatidylcholine, DMPC) alone or phospholipids and LPC as described herein were prepared by mixing an amount of stock gel and an amount of homogenized lipid solution (prepared as described in Example 2) using an overhead stirrer equipped with a stainless steel 6 cm wide "anchor" stir bar.

[0622] The following provides a preparation protocol for an exemplary gel formulation.

[0623] Reference gel containing only HSPCs (also referred to herein as formulation "IM22-743", Table 2, item 7): A gel formulation containing hydrogenated soy phosphatidylcholine lipid (HSPC) was prepared by combining carbomer gel (Carbopol®, deionized water, triethanolamine, and preservatives) to give a 50.64 mM gel with a final gel lipid concentration of 4% w / w as follows:

[0624] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared as follows: 6 grams of Carbopol® 990 was added to deionized water (370 grams) at room temperature, and the mixture was homogenized at 9K RPM for 7 minutes, followed by the addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0625] Dissolution of lipids in ethanol: 55 grams of ethanol AR at 57°C was added to a 250 ml flask. HSPC (2.75 grams) was added along with a 2.5 cm egg-shaped magnet. Mixing was carried out on an evaporator at 56°C for 30 minutes until complete dissolution was achieved.

[0626] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 56°C, 250 RPM), followed by a second check evaporation, resulting in the formation of a dry lipid cake.

[0627] Hydration with water: 55 grams of deionized water at 60°C was added to a dry flask, which was mixed by evaporator at 60°C for 1 hour.

[0628] Homogenization: The solution was placed in a cylinder immersed in a 65°C bath and homogenized at that temperature using a thin "KINEMATICA" knife at 9K RPM for 40 minutes.

[0629] Gel embedding was carried out for 12 hours after homogenization: 12.5 grams of stock gel was mixed with approximately 50 grams of homogenized solution using an overhead stirrer equipped with a stainless steel "anchor" stir bar.

[0630] The resulting MLV DLS analysis showed a Z-average of 3401±532 nm and a PDI of 0.702±0.26 (see Table 2, item 7 in Example 1 above).

[0631] Reference gel containing only DMPC (also referred to herein as formulation "IM22-736", Table 2, item 8): A gel formulation containing dipalmitoylphosphatidylcholine lipid (DMPC) mixed with carbomer gel (Carbopol®, deionized water, triethanolamine, and preservatives) to give a 59.04 mM gel for a final gel lipid concentration of 4% w / w was prepared as follows.

[0632] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared as follows: 6 grams of Carbopol® 990 was added to deionized water (370 grams) at room temperature, and the mixture was homogenized at 9K RPM for 7 minutes, followed by the addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0633] Dissolving lipids in ethanol: 55 grams of ethanol AR at 37° C. was added to a 250 ml flask. DMPC (2.75 grams) was added to the flask and mixed on a rotary evaporator at 37° C. until complete dissolution was achieved.

[0634] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 38°C, 250 RPM), followed by a second check evaporation, resulting in the formation of a dry lipid cake.

[0635] Water hydration: 55 grams of deionized water at 38°C was added to the dry flask and mixing was carried out at the above temperature for 1 hour.

[0636] Homogenization: The solution was placed in a cylinder immersed in a 38°C bath and homogenized for 2 hours.

[0637] The resulting MLV DLS analysis showed a Z-average of 1461±150 nm and a PDI of 0.321±0.27 (see Table 2, item 8 in Example 1 above).

[0638] Gel embedding was performed using 12.5 grams of stock gel mixed with 50.20 grams of homogenized solution using an overhead stirrer equipped with a stainless steel "anchor" type stir bar.

[0639] Reference gel containing 5% w / w glycerin (also referred to herein as formulation "IM22-587"): A reference 5% w / w glycerin gel formulation comprising carbomer gel (Carbopol®, deionized water, triethanolamine and preservatives), glycerin and deionized water. The resulting gel serves as a water retention reference herein, while the incorporation of 5% w / w glycerin in any cosmetic preparation serves as a general water retention standard.

[0640] Gel Preparation: A pre-made gel stock (IM22-579 - 1.5% Carbopol® content) was prepared as follows: 15 grams of Carbopol® 990 was added to deionized water (930 grams) at room temperature, and the mixture was homogenized at 9K RPM for 7 minutes, followed by the addition of preservatives (40 grams of phenoxyethanol and caprylyl glycol mixture) and mixing. 15.00 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 5.72.

[0641] The final preparation was made by combining 37.4g stock gel (IM22-579) with 9.39 grams of glycerin USP and 140.8 grams of deionized water and mixing using an overhead stirrer equipped with a stainless steel "anchor" type stir bar until the pH reached 6.39.

[0642] Gel containing liposomes based on LPC (long chain) and HSPC (also referred to herein as formulation IM22-777, Table 2, item 4): A gel formulation containing multilamellar vesicles composed of hydrogenated soy phosphatidylcholine lipid (HSPC), LPC IM22-1054 (see Table 1), and water, mixed with carbomer gel (Carbopol®, deionized water, triethanolamine, and preservatives) to give a 44.80 mM gel for a final gel lipid concentration of 4% w / w, was prepared as follows.

[0643] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared by adding 6 grams of Carbopol® 990 to deionized water (370 grams) at room temperature and homogenizing the mixture at 9K RPM for 7 minutes, followed by addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0644] Dissolving lipids in ethanol: 55 grams of ethanol AR at 65°C was added to a 250 ml flask. An exemplary LPC (0.33 grams, IM22-1054, see Table 1 above) was weighed into the flask, followed by HSPC (2.41 grams). A 2.5 cm egg-shaped magnet was added to the flask, and mixing was carried out at 65°C for 30 minutes until a uniform, clear solution was obtained.

[0645] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 35°C, -2 tilt, 250 RPM) followed by a second check evaporation to form a dry lipid cake.

[0646] Water Hydration: 55 grams of deionized water at 65°C was added to a dry flask with a 2.5 cm magnet and stirring was achieved at 65°C for 1 hour.

[0647] Homogenization: The solution was placed in a cylinder immersed in a 65°C bath and homogenized at that temperature using a thin "Kinematica" knife at 6-9K RPM for 30 minutes. The resulting MLV DLS analysis showed a Z-average of 420±3 nm and a PDI of 0.304±0.016. See Table 2, item 4 in Example 1 above.

[0648] Gel Embedding: 12.56 grams of stock gel was mixed with 50.64 grams of homogenized solution using an overhead stirrer equipped with a stainless steel "anchor" type stir bar.

[0649] Figures 2A-B present graphs showing the corneometry (water retention) of IM22-777 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (Figure 2A) and various lipid standards (IM22-743 and IM22-736) (Figure 2B).

[0650] FIG. 2C presents the TEWL of IM22-777 as a function of time in comparison with various lipid standards (IM22-743 and IM22-736) and also in comparison with IM22-587, a glycerol standard.

[0651] Gel containing liposomes based on LPC (long chain) and HSPC (also referred to herein as formulation IM22-778, Table 2, item 3): A gel formulation containing multilamellar vesicles composed of hydrogenated soy phosphatidylcholine lipid (HSPC), LPC IM22-1054 (see Table 1), and water, mixed with carbomer gel (Carbopol®, deionized water, triethanolamine, and preservatives) to give a 44.80 mM gel for a final gel lipid concentration of 4% w / w, was prepared as follows.

[0652] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared by adding 6 grams of Carbopol® 990 to deionized water (370 grams) at room temperature and homogenizing the mixture at 9K RPM for 7 minutes, followed by addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0653] Dissolving lipids in ethanol: 55 grams of ethanol AR at 65°C was added to a 250 ml flask. An exemplary LPC (0.52 grams, IM22-1055, see Table 1 above) was weighed into the flask, followed by HSPC (2.42 grams). A 2.5 cm oval magnet was added to the flask, and mixing was carried out at 65°C for 10 minutes until a uniform, clear solution was obtained.

[0654] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 35°C, -2 tilt, 250 RPM) followed by a second check evaporation to form a dry lipid cake.

[0655] Water Hydration: 55 grams of deionized water at 65°C was added to a dry flask with a 2.5 cm magnet and stirring was carried out at 65°C for 1 hour.

[0656] Homogenization: The solution was placed in a cylinder immersed in a 65°C bath and homogenized at that temperature using a thin "Kinematica" knife at 7K RPM for 40 minutes. The resulting MLV DLS analysis is presented in Table 2, Item 3 in Example 1 above.

[0657] Gel Embedding: 12.56 grams of stock gel was mixed with 50.64 grams of homogenized solution using an overhead stirrer equipped with a stainless steel "anchor" type stir bar.

[0658] Figures 3A-B present graphs showing the corneometry (water retention) of IM22-778 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (Figure 3A) and various lipid standards (IM22-743 and IM22-736) (Figure 3B).

[0659] FIG. 3C presents the TEWL of IM22-778 as a function of time in comparison with various standards.

[0660] Gel containing liposomes based on LPC (long chain) and DMPC (also referred to herein as formulation "IM22-754", Table 2, item 5): A gel formulation containing multilamellar vesicles composed of dipalmitoylphosphatidylcholine lipid (DMPC), LPC IM22-1054 (see Table 1), and water, mixed with carbomer gel (Carbopol®, deionized water, triethanolamine, and preservatives) to give a 102.32 mM gel for a final gel lipid concentration of 4% w / w, was prepared as follows.

[0661] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared as follows: 6 grams of Carbopol® 990 was added to deionized water (370 grams) at room temperature, and the mixture was homogenized at 9K RPM for 7 minutes, followed by the addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0662] Dissolving lipids in ethanol: 55 grams of ethanol AR at 34°C was added to a 250 ml flask. LPC (IM22-1054 (see Table 1), 1.51 grams) was added to the flask, followed by DMPC (4.74 grams). A 2.5 cm egg-shaped magnet was added to the flask, and mixing was carried out at 35°C until a homogeneous, clear solution was obtained.

[0663] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 40°C, -2 tilt, 250 RPM), followed by a second check evaporation, resulting in the formation of a dry lipid cake.

[0664] Water hydration: 55 grams of deionized water at 34°C was added to a dry flask with a 2.5 cm magnet and stirring was applied at 34°C for 2 hours.

[0665] The resulting MLV DLS analysis showed a Z-average of 676.8±41 nm and a PDI of 0.622±0.047 (see Table 2, item 5 in Example 1 above).

[0666] Gel Embedding: 12.5 grams of stock gel was mixed with 50.0 grams of homogenized solution using an overhead stirrer with a stainless steel "anchor" type stir bar.

[0667] Figures 4A-B present graphs showing the corneometry (water retention) of IM22-754 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (Figure 4A) and various lipid standards (IM22-743 and IM22-736) (Figure 4B).

[0668] FIG. 4C presents the TEWL of IM22-754 as a function of time in comparison with various standards.

[0669] Gel containing liposomes based on LPC (long chain) and DMPC (also referred to herein as formulation "IM22-744", Table 2, item 6): A gel formulation containing multilamellar vesicles composed of dipalmitoylphosphatidylcholine lipid (DMPC), LPC IM22-1054 (see Table 1 in Example 1), and water, mixed with carbomer gel (Carbopol®, deionized water, triethanolamine, and preservatives) to give a 51.16 mM gel for a final gel lipid concentration of 4% w / w, was prepared as follows.

[0670] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared as follows: 6 grams of Carbopol® 990 was added to deionized water (370 grams) at room temperature, and the mixture was homogenized at 9K RPM for 7 minutes, followed by the addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0671] Dissolving lipids in ethanol: 55 grams of ethanol AR at 34°C was added to a 250 ml flask. LPC (IM22-1054, 0.76 grams) was added to the flask, followed by DMPC (2.37 grams). A 2.5 cm oval magnet was added to the flask, and mixing was carried out at 26°C for 30 minutes until a homogeneous, clear solution was obtained.

[0672] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 40°C, -2 tilt, 250 RPM), followed by a second check evaporation, resulting in the formation of a dry lipid cake.

[0673] Water hydration: 55 grams of deionized water at 26°C was added to a dry flask with a 2.5 cm magnet and stirring was carried out at 26°C for 2 hours.

[0674] The resulting MLV DLS analysis showed a Z-average of 983±63.3 nm and a PDI of 0.726±0.003 (see Table 2, item 6 in Example 1 above).

[0675] Gel Embedding: 12.5 grams of stock gel was mixed with 50 grams of homogenized solution using an overhead stirrer equipped with a stainless steel stir bar.

[0676] Figures 5A-B present graphs showing the corneometry (water retention) of IM22-754 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (Figure 5A) and various lipid standards (IM22-743 and IM22-736) (Figure 5B).

[0677] Gel containing liposomes based on LPC (short chain) and DMPC (also referred to herein as formulation "IM22-732", Table 2, item 9): A gel formulation containing multilamellar vesicles composed of carbomer gel (dipalmitoylphosphatidylcholine lipid (DMPC), LPC IM22-1053, see Table 1) and water, which was mixed with Carbopol®, deionized water, triethanolamine, and preservatives to give a 54.60 mM gel for a final gel lipid concentration of 4% w / w, was prepared as follows.

[0678] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared as follows: 6 grams of Carbopol® 990 was added to deionized water (370 grams) at room temperature, and the mixture was homogenized at 9K RPM for 7 minutes, followed by the addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0679] Dissolving lipids in ethanol: 55 grams of ethanol AR at 38°C was added to a 100 ml flask while rotating on a rotary evaporator. LPC (0.21 grams, IM22-1053) was added to the flask, followed by DMPC (2.53 grams). Mixing was carried out at 38°C for 10 minutes until a homogeneous, clear solution was obtained.

[0680] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 40°C, -2 tilt, 250 RPM), followed by a second check evaporation, resulting in the formation of a dry lipid cake.

[0681] Water hydration: 55 grams of deionized water at 37°C was added to a dry flask with a 2.5 cm magnet and stirring was carried out at 37°C for 1 hour.

[0682] Homogenization: The solution was placed in a cylinder immersed in a 37°C bath and homogenized at that temperature using a wide "Kinematica" knife at 9K RPM for 1 hour.

[0683] The resulting MLV DLS analysis is shown in Table 2, Entry 9 in Example 1 above.

[0684] Gel Embedding: 12.54 grams of stock gel was mixed with approximately 50 grams of homogenized solution using an overhead stirrer equipped with a stainless steel "anchor" type stir bar.

[0685] FIG. 6 presents a graph showing the corneometry (water retention) of IM22-732 gel formulations as a function of time in comparison to various lipid standards (IM22-743 and IM22-736).

[0686] Gel containing liposomes based on LPC (medium chain) and DMPC (also referred to herein as formulation "IM22-782", Table 2, item 1): A gel formulation containing multilamellar vesicles composed of dipalmitoylphosphatidylcholine lipid (DMPC), LPC IM22-1063 (see Table 1 in Example 1 above), and water, mixed with carbomer gel (Carbopol®, deionized water, triethanolamine, and preservatives) to give a 54.16 mM gel for a final gel lipid concentration of 4% w / w, was prepared as follows.

[0687] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared as follows: 6 grams of Carbopol® 990 was added to deionized water (370 grams) at room temperature, and the mixture was homogenized at 9K RPM for 7 minutes, followed by the addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0688] Dissolving lipids in ethanol: 55 grams of ethanol AR at 35°C was added to a 250 ml flask. LPC (IM22-1063, 0.24 grams) was added, followed by DMPC (2.52 grams) along with a 2.5 cm egg-shaped magnet. Mixing was carried out on an evaporator at 35°C for 10 minutes until complete dissolution was achieved.

[0689] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water set at 40°C, 250 RPM), followed by a second check evaporation, resulting in the formation of a dry lipid cake.

[0690] Water Hydration: 55 grams of deionized water at 35°C was added to a dry flask, which was mixed in a 35°C bath using a magnet in the flask for 1 hour.

[0691] Homogenization: Using a thin "Kinematica" knife, in a 36°C bath at 8.0K RPM for 1 hour, then left to defoam for 3 days.

[0692] The resulting MLV DLS analysis is presented in Table 2, Entry 1 in Example 1 above.

[0693] Gel embedding was performed using 12.50 grams of stock gel mixed with approximately 49.99 grams of homogenized solution using an overhead stirrer equipped with a stainless steel "anchor" stir bar.

[0694] Figures 7A-B present graphs showing the corneometry (water retention) of IM22-782 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (Figure 7A) and various lipid standards (IM22-743 and IM22-736) (Figure 7B).

[0695] FIG. 7C presents the TEWL of IM22-782 as a function of time in comparison with various standards.

[0696] Gel containing liposomes based on LPC (medium chain) and soybean-derived phosphatidylcholine (PC S 100) (also referred to herein as formulation "IM22-780"; Table 2, item 2: A gel formulation containing multilamellar vesicles composed of soy-derived phosphatidylcholine (PC S 100), LPC IM22-1056 (see Table 1 in Example 1 above), and water, mixed with carbomer gel (Carbopol®, deionized water, triethanolamine, and preservatives) to give a 46.4 mM gel with a final gel lipid concentration of 4% w / w, was prepared as follows.

[0697] Gel Preparation: A pre-made gel stock (IM22-728-1.5% Carbopol® content) was prepared as follows: 6 grams of Carbopol® 990 was added to deionized water (370 grams) at room temperature, and the mixture was homogenized at 9K RPM for 7 minutes, followed by the addition of preservative (approximately 16 grams of "Cosphagard CAP") and mixing. 6.71 grams of triethanolamine was then added to neutralize the acidic carbomer to a pH of 6.17.

[0698] Dissolving lipids in ethanol: 55 grams of ethanol AR at 65°C was added to a 250 ml flask. LPC (0.25 grams, IM22-1056) was added, followed by DMPC (2.50 grams) along with a 2.5 cm egg-shaped magnet. Mixing was carried out on an evaporator at 65°C for 30 minutes until complete dissolution was achieved.

[0699] Ethanol evaporation: The solution was evaporated to dryness using a "BUCHI" rotary evaporator (water bath set at 60°C, 250 RPM), followed by a second confirmation evaporation, resulting in the formation of a dry lipid cake.

[0700] Water Hydration: 55 grams of deionized water at 65°C was added to a dry flask, which was mixed in a 65°C bath using a magnet in the flask for 1 hour.

[0701] Gel embedding was performed using 12.50 grams of stock gel mixed with approximately 50.03 grams of homogenized solution using an overhead stirrer equipped with a stainless steel "anchor" stir bar.

[0702] The resulting MLV DLS analysis is presented in Table 2, Entry 2 in Example 1 above.

[0703] Figures 8A-B present graphs showing the corneometry (water retention) of IM22-780 gel formulations as a function of time in comparison with the glycerin reference IM22-587 (Figure 8A) and various lipid standards (IM22-743 and IM22-736) (Figure 8B).

[0704] Table 3 below summarizes the lipid composition of the gel formulations described above. "PC lipid" stands for bilayer-forming phospholipid. LPC %w / w refers to the weight % of LPC relative to the total weight of the formulation.

[0705] [Table 3]

[0706] Example 3 Cosmetic cream preparations A cream formulation comprising multilamellar vesicles composed of DMPC and LPC as described in Example 1 above mixed with water, glycerin, cetearyl alcohol (and) cetearyl glucoside, caprylic / capric triglyceride, isononyl isononanoate, Simmondsia chinensis (jojoba) seed oil, Butyrospermum Parkii (shea) butter, Cocos nucifera (coconut) oil, sodium polyacrylate, phenoxyethanol, glycol caprylate, tocopheryl acetate, and fragrance at a lipid concentration of 4 mM is prepared as follows:

[0707] Preparation of Multilamellar Vesicles: Multilamellar vesicles (MLVs) are prepared by adding selected LPCs and selected phospholipids in a selected weight ratio to a flask containing ethanol AR, dissolving these ingredients until completely dissolved, and evaporating in a 37°C bath to form a dry lipid cake. The formed lipid cake is then hydrated with deionized water and stirred with a magnet for, e.g., 1 hour at, e.g., 1500 RPM.

[0708] Phase A: Add water and glycerin to a vessel and heat to 70°C. Phase B: 5.00% Cetearyl Alcohol (and) Cetearyl Glucoside, 1.70% Caprylic / Capric Triglyceride, 2.70% Isononyl Isononanoate, 0.80% Simmondsia chinensis (Jojoba) Seed Oil, 0.35% Butyrospermum parkii (Shea) Butter, 0.20% Cocos nucifera (Coconut) Oil are added to a container and heated to 70°C.

[0709] Dispersion of Phase A+B: Add Phase A to Phase B and immediately homogenize, e.g., for 10 minutes at 10-15K RPM, e.g., using a wide "Kinematica" knife, until one phase is formed. Add 0.20% sodium polyacrylate at a temperature below 60°C and homogenize the solution again for 5 minutes. Cool the resulting preparation with stirring using an overhead stirrer until it is below 40°C. Then add 10.00% MLV, 0.80% phenoxyethanol and caprylyl glycol, 0.10% tocopherol acetate, and 0.03% fragrance with stirring.

[0710] A short homogenization period (2 min) is then carried out.

[0711] Example 4 Skin hydration Materials and Methods: A gel formulation was prepared as in Example 2 above.

[0712] The formulations were applied to human skin. Transepidermal water loss (TEWL) and corneometry measurements were determined using a Courage+Khazaka MPA 6 multi-probe adapter system using the test procedure provided below. The TEWL technique is based on measuring the flux of water molecules evaporating from treated skin. The measurement procedure was performed three times, separately for each formulation, at three locations on each skin segment. Measurements were compared to naive skin to demonstrate the fading effects of the treatment. Additionally, the effectiveness of the gel formulation was compared to commercially available acceptable moisturizers containing hyaluronic acid, propylene glycol, and glycerin.

[0713] Skin hydration was also determined by corneometry.

[0714] Human skin was obtained from a donor (female, 37 years old) through aesthetic abdominal plastic surgery with her consent. The subcutaneous fat layer was removed, and the skin was kept delipidated (full thickness) at -20°C until use (less than 3 months, ensuring its barrier function). This study was performed on full-thickness human skin (epidermis + dermis). 16 test items were evaluated in this experiment.

[0715] Both TEWL and skin hydration were assessed by corneometry. TEWL is the amount of water passively evaporated through the skin to the external environment due to the water vapor pressure gradient across the skin barrier and is used to characterize skin barrier function. Skin hydration was determined by epidermal conductivity, which correlates with skin water content.

[0716] On the day of the experiment, the skin was thawed at room temperature and the dermal side was placed in PBS for 30 minutes for equilibration. The epidermal side was gently dried and topical application was performed by massaging the area to be treated (200 ml / cm). 2 Due to the large number of test groups, the experiment was carried out over three days using the same skin donor, and the samples and their respective naive groups were tested on the same day.

[0717] TEWL and skin hydration (corneometry) were determined kinetically at 0, 10, 30, 60, 120, 180, and 240 min after application according to the manufacturer's instructions after electrode calibration. pH was measured kinetically in the naive group at the same time points as above.

[0718] Data Analysis and Results: TEWL measurements correlate with water leaving the skin, so a lower result means less water leaving the skin and better hydration compared to the naive, untreated sample.

[0719] Corneometry measurements indicate the hydration level of the surface layer of the skin (stratum corneum) by measuring the skin's dielectric properties. Measurements are performed by applying a probe to the skin surface. Upon contact, an electric field passes through the stratum corneum, obtaining the dielectric constant. The value of the dielectric constant (in arbitrary units) is directly proportional to the hydration level of the skin.

[0720] Data obtained for exemplary test formulations are shown in Figures 2A-8B and in Tables 4 (TEWL) and 5 (corneometry) below.

[0721] [Table 4]

[0722] [Table 5]

[0723] The purpose of this study was to evaluate the efficacy of newly designed formulations. Ten formulations were evaluated, along with two formulations (IM22-743 and IM22-736) that served as references for lipid water-holding capacity without LPC.

[0724] Skin hydration and TEWL were measured kinetically over 240 minutes after exposure to the formulations.

[0725] As can be seen from the data presented in Figures 2A-8B and Tables 4 and 5, at short exposure times (up to 30 minutes), all formulations enhanced hydration parameters compared to naive levels. At 30 and 60 minutes, a decrease in skin hydration was observed. After 120 minutes, a plateau was observed for all compounds. These findings demonstrate the significant ability of the tested formulations to enhance the skin's barrier properties, thereby reducing overall water loss, indicating the high efficacy of these formulations.

[0726] Example 5 Synthetic moisture retention layer lasts on dry skin Materials and Methods: Water retention was measured using two techniques: analytical balance (OHAUS, EQ-238) and NMR-MOUSE (ACT-Magritek GmbH, Aachen, Germany).

[0727] 125.5mm 2 The analytical balance was determined by depositing gel to completely fill a 3 mm deep cell with an area of ​​1 mm and measuring the mass loss over time using an NMR-MOUSE. The mass loss measurement reveals the evaporation rate from the sample. To reduce the contribution of variability to mass loss due to manual application, this rate is determined from the corresponding slopes for the first hour and 10 minutes after application. During the first hour, for this thickness of deposited gel, the rate (slope) is safely constant and can be attributed to the evaporation of unbound water.

[0728] NMR-MOUSE measurements were performed on skin from pig ears. Upon arrival, small pieces of ear skin containing the dermis and epidermis were cut and frozen at -20°C. Before each measurement, the small pieces were thawed at room temperature and dried with blotting paper for several minutes. Next, a gel formulation was deposited on a portion of the sample after the measurement. The gel formulation was applied to a marked circular area with a diameter of 19 mm using a wooden ice stick.

[0729] The NMR-MOUSE is equipped with a permanent magnet and surface radio frequency (RF) coils for transmitting and receiving. See Nicasy et al., Polymers 2022, 14, 798, and Bergman et al., NMR Biomed. 2015, 28, 656-666. A U-shaped magnet provides a strong gradient of approximately 8 T / m along the z-direction away from the magnet face. This strong Z-gradient, in combination with hard RF pulses, produces selective excitation of a thin, flat section several hundred micrometers thick, located 25 mm from the magnet. The static magnetic field in this 25 mm space is approximately 0.3 T (resonance frequency approximately 13.6 MHz). The cross-sectional diameter of the RF beam was estimated to be 0.6–0.7 mm. A Carr-Meiboom-Purcell-Gill (CMPG) train of RF pulses was used to tilt the magnetization 90° relative to the transverse plane and probe its echoes.

[0730] The following formulations were tested: IM23-587 (5% w / w glycerin in gel) IM22-736 (DMPC in gel only), IM22-732 (DMPC+LPC gel)

[0731] Experimental steps: Step 1: To confirm that protons are being sampled from water, a clear signal was obtained at ν=13.67 MHz from a 5 mM CuSO4 solution in a glass bottle.

[0732] Step 2: To find the signal from the protons in the gel, the gel formulation was spread on a Petri dish with a lid. Again, a clear signal was observed at ν=13.67 MHz. Note that the optimal sample height and RF intensity (when the pulse duration was fixed) needed to be determined to optimize the signal acquisition.

[0733] Step 3: To save time in finding the optimal height in advance and measuring the loss rate on the skin, the gel was spread on the substrate and covered with nylon.

[0734] Step 4: For reference, the gel was removed from the plastic substrate with paper and ethanol, and the dried skin was fastened to the substrate with red tape (see Figure 3). The magnetization signal was then measured.

[0735] Step 5: After a short signal optimization period (1-2 min), the rate of water loss was measured by spreading the gel onto the clamped synthetic skin. The rate of water loss was stopped after 2 h.

[0736] Step 6: The gel was wiped off the clamped skin with paper and ethanol, and the magnetization signal was measured.

[0737] Step 7: Another reference sample of dry skin was clamped and the magnetization signal was measured.

[0738] Figure 10A shows the magnetization signals from water protons for three samples spread on pig skin samples taken from the ear. Negative time corresponds to the pre-deposition state. A calibration procedure to optimize the signal was performed for the first 30 minutes after glycerin deposition. The difference in signal intensity immediately after deposition cannot be explained by the difference in the amount of water deposited, but rather by the characteristic decay of the echo signal, which can be attributed to different relaxation times T2, proton diffusion, and exchange processes, as shown in Figure 10B. This also applies to the higher pre-deposition signal from the DMPC sample compared to DMPC-LPC. Therefore, as seen in Figures 9A-9B, each curve was normalized by its initial intensity immediately after deposition, i.e., M(t) / M(0). For the glycerin sample, M(t = 0) was derived from the intercept point in the fitted linear equation.

[0739] The behavior of the curves in Figures 9A-9B exhibits three characteristic regimes. Measurements in the first regime, from t = 0 min to 74, 44, and 56 min for glycerol / DMPC / DMPC-LPC, respectively, are represented by the circles and corresponding fitted linear curves (dotted lines). The signal decrease in this regime is primarily due to the evaporation process of unbound (i.e., weakly bound) water molecules.

[0740] Another way to estimate the evaporation rate of each substance without skin effect is by measuring the weight loss using an analytical balance, as shown in Figure 11. Both Figures 9A-9B and 11 show curves with different slopes corresponding to the evaporation rate.

[0741] When the cell size, deposited volume, spreading area, and duration of evaporation are known, the average shrinkage rate in μm / min can be determined. The results are summarized in Table 6 below. The slope values ​​are calculated by fitting a straight line (R ) to the curves in Figures 9A-9B from 10 minutes after deposition (to reduce spreading variability) to 60 minutes (to safely stay in the linear regime). 2 >0.996).

[0742] For the evaporation cell on the analytical balance, the slope can only be attributed to water evaporation. Indeed, the glycerin sample is seen to lose its water most rapidly, while DMPC-LPC retains water for the longest time. The same trend is observed for the shrinkage rates estimated from MOUSE-NMR. Note that in MOUSE-NMR, other processes such as skin penetration and effective T2 signal attenuation can affect the results. Nevertheless, it can be seen that the DMPC-LPC treatment consistently has the lowest nominal shrinkage rate, indicating that its unbound water molecules persist there for the longest time.

[0743] 9A-9B, a change in slope is observed for all samples, with the slope becoming more gradual before evaporation is complete. As evaporation continues, other processes become dominant as increasing concentration affects water retention capacity and effective T as well. This indicates that the magnetization technique reveals the bound or embedded water regime.

[0744] The third regime (represented by triangles in Figures 9A-9B) is typified by a plateau for the glycerol and DMPC samples and a wide range of values ​​for the DMPC-LPC sample, and is therefore likely due to a steady state of embedded water levels.

[0745] Figure 9B shows the embedded water regime: the slope for DMPC-LPC (represented by triangles) is again the shallowest, pointing to its ability to retain water for longer periods of time.

[0746] The data obtained show that DMPC-LPC outperforms other formulations tested in terms of skin hydration, in both the unbound and embedded water regimes, as measured by two techniques.

[0747] Glycerin has the smallest size and is therefore expected to have the greatest penetration into the stratum corneum of skin. This is a property utilized for optical clearance in Raman spectroscopy measurements of skin. DMPC, on the other hand, forms liposomes and multilamellar vesicles (MLVs) in which hydrophilic groups (carbonyl and phosphate groups) pointing radially inward and outward bind water molecules. Its penetration into skin is expected to be shallower than that of glycerin due to its much larger size (100 nm to 1000 nm). In the case of DMPC-LPC, the LPC polymer contributes hydrophilic amide groups in addition to carbonyl and phosphate groups that also bind water molecules. Its penetration is also expected to be shallower. Furthermore, as the concentration increases with water evaporation, a thin polymeric film (or polymeric colloid) is formed in the case of DMPC-LPC, trapping water. This film effectively traps water for a longer period of time, making DMPC-LPC an excellent humectant.

[0748] [Table 6]

[0749] While the present invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, the present invention is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and broad scope of the appended claims.

[0750] It is the intention of the applicants that all publications, patents, and patent applications referenced herein be incorporated by reference in their entireties as if each individual publication, patent, or patent application was specifically and individually referred to when referenced. Furthermore, citation or identification of any reference in this application shall not be construed as an admission that the reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. Additionally, the priority documents of this application are incorporated herein by reference in their entireties.

Claims

1. 1. A cosmetic or cosmeceutical composition (or formulation) comprising a liposome and a cosmetically acceptable carrier, wherein the liposome comprises: a) at least one bilayer-forming lipid, and b) a polymeric compound having the general formula I 1. A cosmetic or cosmeceutical composition (or formulation) comprising: 【Chemical 1】 (In the formula, m is zero or a positive integer; n is an integer that is at least 2, at least 5, and preferably at least 10 (e.g., from 10 to 200); Y is a skeleton unit that forms the polymer skeleton of the polymer compound, L is absent or a linking moiety; Z has the general formula II: 【Chemistry 2】 (In the formula, The wavy lines represent the points of attachment to the corresponding Y backbone unit; A is a substituted or unsubstituted hydrocarbon; B is an oxygen atom or is absent; R １ ~R ３ are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heteroalicyclic, aryl, and heteroaryl, and X is a lipid moiety represented by formula IV. 【Chemistry 3】 (In the formula, F １ , F ２ , F ３ and F ４ are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, acyl, alkoxy, thioalkoxy, carboxy, and thiocarboxy; F １ , F ２ , F ３ and F ４ is not hydrogen and is at least 10 carbon atoms in length; J is —O—P(═O)(OH)—O— or is absent; K is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length or is absent; M is a linking group selected from the group consisting of -O-, -S-, amino, sulfinyl, sulfonyl, phosphate, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, urea, thiourea, carbamyl, thiocarbamyl, amido, carboxy, and sulfonamido, or is absent; and Q is a substituted or unsubstituted hydrocarbon of 1 to 10 carbon atoms in length or is absent; When M does not exist, Q does not exist, and J does not exist, then M does not exist; provided that when J is —O—P(═O)(OH)—O—, then M is other than an amide and / or Q includes an aryl moiety.

2. F １ , F ２ , F ３ and F ４ 10. The cosmetic or cosmeceutical composition of claim 1, wherein at least one of is an alkoxy, thioalkoxy, acyl, or carboxy having a length of at least 10 carbon atoms.

3. F １ , F ２ , F ３ and F ４ 3. The cosmetic or cosmeceutical composition according to claim 1, wherein at least one of the following is derived from a fatty acid selected from the group consisting of lauroyl, myristoyl, palmitoyl, stearoyl, palmitoleoyl, oleoyl and linoleoyl.

4. The cosmetic or cosmeceutical composition according to any one of claims 1 to 3, wherein M is carboxy.

5. The cosmetic or cosmeceutical composition according to any one of claims 1 to 4, wherein K is alkyl.

6. 3. The cosmetic or cosmeceutical composition of claim 1 or 2, wherein J is -P(=O)(OH)-O-, M is an amide, and Q is a hydrocarbon substituted with at least one aryl (e.g., phenyl).

7. The cosmetic or cosmeceutical composition according to any one of claims 1 to 6, wherein Q is methylene substituted with at least one aryl.

8. The cosmetic or cosmeceutical composition according to any one of claims 1 to 7, wherein J is absent.

9. The cosmetic or cosmeceutical composition according to any one of claims 1 to 7, wherein J and K are each absent.

10. The cosmetic or cosmeceutical composition according to any one of claims 1 to 7, wherein J and K are each absent and M is carboxy.

11. F １ , F ２ , F ３ and F ４ The cosmetic or cosmeceutical composition according to any one of claims 1 to 10, wherein at least one or at least two of are each independently thioalkoxy.

12. F １ , F ２ , F ３ and F ４ The cosmetic or cosmeceutical composition according to any one of claims 1 to 10, wherein at least one or at least two of are each independently carboxy.

13. F １ and F ２ At least one or both of the following is carboxy; and F ３ and F ４ 13. The cosmetic or cosmeceutical composition of claim 12, wherein at least one of is alkyl.

14. A cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 13, wherein Y is a substituted or unsubstituted alkylene unit.

15. 15. The cosmetic or cosmeceutical composition (or formulation) of claim 14, wherein Y is a substituted or unsubstituted ethylene unit.

16. The cosmetic or cosmeceutical composition (or preparation) according to any one of claims 1 to 15, wherein B is an oxygen atom.

17. A cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 16, wherein A is a substituted or unsubstituted hydrocarbon of 1 to 4 carbon atoms in length.

18. 18. The cosmetic or cosmeceutical composition (or formulation) of claim 17, wherein A is a substituted or unsubstituted ethylene group.

19. R １ ~R ３ are each independently hydrogen or C １～４ 19. The cosmetic or cosmeceutical composition (or preparation) according to any one of claims 1 to 18, wherein the aryl group is - alkyl.

20. R １ ~R ３ 20. The cosmetic or cosmeceutical composition (or formulation) of claim 19, wherein each is methyl.

21. A cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 20, wherein n is in the range of 10 to 200.

22. A cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 21, wherein n is at least 30.

23. 22. The cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 21, wherein n is in the range of 30 to 70 or 30 to 60.

24. The cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 21, wherein n is at least 50 or at least 60.

25. The cosmetic or cosmeceutical composition (or formulation) according to any one of the preceding claims, wherein n is in the range of 50 to 150, or 60 to 150, or 50 to 80, or 60 to 80.

26. A cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 21, wherein n is in the range of 60 to 80.

27. 22. The cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 21, wherein n is at least 80, or in the range of 80-150 or 80-120.

28. A cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 27, wherein m is in the range of 0 to 50.

29. A cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 28, wherein at least some of the backbone units Y, L and / or Z comprise at least one targeting moiety.

30. 30. The cosmetic or cosmeceutical composition (or formulation) according to any one of claims 1 to 29, wherein the molar ratio of the bilayer-forming lipid to the polymeric compound is in the range of 5:1 to 5,000:1, or 10:1 to 1,000:1, or 10:1 to 100:1, or 10:1 to 50:1, or 100:1 to 200:

1.

31. 31. The cosmetic or cosmeceutical composition according to any one of claims 1 to 30, comprising a plurality of liposomes, at least some of which comprise a plurality of liposomes according to claim 1.

32. 32. The cosmetic or cosmeceutical composition of claim 31, wherein the liposomes have a polydispersity index of less than 1, or less than 0.8, or less than 0.

6.

33. 33. The cosmetic or cosmeceutical composition according to any one of the preceding claims, wherein the liposomes have an average diameter in the range of 50 to 5,000 nm, or 500 to 5,000 nm, or 500 to 3,500 nm, or 200 to 2,000 nm, or 200 to 1,000 nm, or 400 to 1,000 nm, or 400 to 800 nm.

34. 34. The cosmetic or cosmeceutical composition according to any one of claims 1 to 33, wherein the amount of the bilayer-forming lipid in the composition is in the range of 0.1 to 5 wt.% of the total weight of the composition.

35. 35. The cosmetic or cosmeceutical composition according to any one of claims 1 to 34, wherein the weight ratio of the bilayer-forming lipid to the polymeric compound is in the range of from 1:1 to 3,000:1, or from 1:1 to 1,000:1, or from 1:1 to 500:1, or from 1:1 to 300:1, or from 1:1 to 100:1, or from 1:1 to 50:1, or from 5:1 to 50:1, or from 5:1 to 30:

1.

36. A cosmetic or cosmeceutical composition according to any one of claims 1 to 35, formulated for topical application.

37. The cosmetic or cosmeceutical composition according to any one of claims 1 to 36, wherein the carrier comprises an aqueous liquid.

38. 38. The cosmetic or cosmeceutical composition of claim 37, wherein the liposomes are contained in the aqueous liquid.

39. 39. The cosmetic or cosmeceutical composition according to any one of claims 1 to 38, wherein the carrier forms a composition in the form of a cream, an ointment, a gel, a lotion, a soap, a shampoo, a water-in-oil emulsion, an oil-in-water emulsion, a water-in-oil-in-water emulsion, an oil-in-water-in-oil emulsion.

40. The cosmetic or cosmeceutical composition according to any one of claims 1 to 38, in the form of a gel.

41. 41. The cosmetic or cosmeceutical composition of claim 40, wherein the total amount of the bilayer-forming lipid and the polymeric compound is in the range of 1 to 10 or 1 to 5 wt. % of the total weight of the composition.

42. A skin care product comprising a cosmetic or cosmeceutical composition according to any one of claims 1 to 41.

43. A composition according to any one of claims 1 to 41 or a skin care product according to claim 42, for moisturizing the skin.

44. A composition according to any one of claims 1 to 41 or a skin care product according to claim 42 for the treatment of damaged keratinous tissue.

45. A method of providing cosmetic care to a subject in need thereof, comprising applying (e.g., topically) an effective amount of a cosmetic composition according to any one of claims 1 to 41 or a skin product according to claim 42 to the skin surface of the subject, thereby providing said cosmetic care.

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