WO2024178023A1

WO2024178023A1 - Macromolecular chemical uv filters

Info

Publication number: WO2024178023A1
Application number: PCT/US2024/016572
Authority: WO
Inventors: Xuefei BAI; Jiajun Yan; Feichen CUI; Zixiao WANG
Original assignee: B.A.I. Laboratories, Llc; Shanghaitech University
Priority date: 2023-02-21
Filing date: 2024-02-20
Publication date: 2024-08-29

Abstract

Disclosed herein are polystyrene, polyacrylate, polyacrylonitrile, polymaleimide, or polymaleic anhydride polymers comprising repeating units having the structure of Formula (I), as well as copolymers and compositions thereof. The polymers, copolymers, and compositions of the present disclosure absorb and/or scatter ultraviolet light and are contemplated as useful for protecting a keratinous substrate, such as skin, from ultraviolet radiation. Methods of using the disclosed polymers, copolymers, and compositions are also disclosed.

Description

MACROMOLECULAR CHEMICAL UV FILTERS

BACKGROUND OF THE DISCLOSURE

[0001] Excessive exposure to ultraviolet (UV) radiation from the sun can cause sunburn, skin aging, and skin cancer. Sunburn is a response to UV-induced damage to DNA that results in inflammation and can trigger DNA repair processes, increased melanin production, and apoptosis in the affected cells/tissues. The mechanisms underlying UV-related skin aging and carcinogenesis include UV-induced reactive oxygen species (ROSs) generation. In turn, UV-induced ROSs can lead to DNA damage, including single- and/or double-strand DNA breaks, base modifications, and DNA crosslinks.

[0002] Sunscreens contain UV attenuators, such as chemical or physical filters, which absorb and/or scatter UV light to prevent damage from UV irradiation. However, chemical sunscreen UV filters can reportedly increase UV-induced ROSs after penetrating the epidermis. Chemical UV filters also contribute to cellular alterations, hormonal disruptions, and carcinogenesis. The U.S. Food and Drug Administration (FDA) has also expressed concerns over coral reef bleaching caused by organic UV filters, such as oxybenzone, octocrylene, and octinoxate. Accordingly, the FDA has labeled other organic UV filters, such as /?-aminobenzoic acid and trolamine salicylate, as unsafe and has requested additional safety data on certain other chemical UV filtering ingredients, leaving no organic UV filters considered as safe and effective by the FDA to date.

[0003] By contrast, the only two ingredients that are considered safe and effective by the FDA are physical UV filters, namely, zinc oxide and titanium dioxide. Zinc oxide and titanium dioxide are widely used as broad-spectrum UV radiation filters in sunscreens. They reduce UV radiation via both scattering and non-irradiative dissipation mechanisms (e.g., reflection). However, the use of such physical UV filters may also generate various ROSs, which, as mentioned above, can cause skin damage.

[0004] Thus, there remains a need for organic chemical UV filters that not only scatter and/or absorb UV-light, but also display low skin permeability. In addition to protecting from damage caused by UV radiation, such chemical UV filters should attenuate the generation of sub-epidermal ROSs and to have improved environmental safety profiles.

SUMMARY OF THE DISCLOSURE

[0005] The present disclosure provides polymers and copolymers, as well as thereof, that absorb and/or scatter ultraviolet light and methods of using such polymers, copolymers, and compositions and methods to protect keratinous substrates, such as skin, from ultraviolet radiation.

[0006] A first aspect of the present disclosure provides a polymer that absorbs and/or scatters ultraviolet light. In some embodiments, the polymer is a polystyrene, polyacrylate, polyacrylonitrile, polymaleimide, or polymaleic anhydride. In some embodiments, the polymer comprises a repeating unit, wherein the repeating unit has the structure of Formula (I), as defined herein, or an isomer or isotopic variant thereof. In some embodiments, the isomer of Formula (I) is an enantiomer or a diastereomer thereof. In some embodiments, the repeating unit has the structure of Formula (I), as defined herein, or an isotopic variant thereof. In some embodiments, the repeating unit has the structure of Formula (I), as defined herein. In some embodiments, the repeating unit has the structure of Formula (I- A), as defined herein, or an isomer or isotopic variant thereof. In some embodiments, the isomer of Formula (I-A) is an enantiomer or a diastereomer thereof. In some embodiments, the repeating unit has the structure of Formula (I-A), as defined herein, or an isotopic variant thereof. In some embodiments, the repeating unit has the structure of Formula (I-A), as defined herein. In some embodiments, the repeating unit has the structure of Formula (I-A-i), as defined herein, or an isotopic variant thereof. In some embodiments, the repeating unit has the structure of Formula (I-A-i), as defined herein.

[0007] A second aspect of the present disclosure provides a copolymer comprising: (i) a first polymer, wherein said first polymer is a polymer of the disclosure; and (ii) one or more additional polymer(s), wherein said one or more additional polymer(s) is/are independently a polystyrene, polyacrylate, polyacrylonitrile, polymaleimide, or polymaleic anhydride, provided that the first polymer and the one or more additional polymer(s) are structurally different. In some embodiments, the copolymer is a block copolymer, random copolymer, or alternating copolymer. In some embodiments, the first polymer comprises a repeating unit, wherein the repeating unit has the structure of Formula (I-A-i), as defined herein, or an isotopic variant thereof. In some embodiments, the one or more additional polymer(s) comprises a repeating unit, wherein the repeating unit has the structure of Formula (II), as defined herein, or an isotopic variant thereof.

[0008] A third aspect of the present disclosure provides composition comprising a polymer or copolymer of the disclosure. In some embodiments, the composition comprises the polymer or copolymer of the disclosure and an acceptable carrier. In some embodiments, the composition is formulated for topical administration. In some embodiments, the composition is in the form of a topical lotion, an oil, a spray, a lip balm, or a make-up cream. [0009] A fourth aspect of the present disclosure provides a method of protecting a keratinous substrate from ultraviolet radiation. In some embodiments, the method comprises applying a polymer, copolymer, or composition of the disclosure to a keratinous substrate of a subject in need thereof. In some embodiments, the keratinous substrate is skin, hair, scalp, or nails.

[0010] A fifth aspect of the present disclosure provides a method of protecting skin from ultraviolet radiation. In some embodiments, the method comprises applying a polymer, copolymer, or composition of the disclosure to the skin of a subject in need thereof.

[0011] Particular embodiments of the disclosure are set-forth in the following numbered paragraphs:

1. A polymer comprising a repeating unit, wherein the repeating unit has the structure of Formula (I):

or an isomer or isotopic variant thereof, wherein:

R¹ is hydrogen, Ci-C₆ alkyl, -C(O)OH, -C(O)O(Ci-C₆ alkyl), or -CN;

R² is hydrogen or Ci-Ce alkyl; or

R¹ and R², together with the carbon atoms to which they are attached, form a pyrrolidine-2, 5-dione or dihydrofuran-2, 5-dione; and

R³ is Ci-Ce alkyl.

2. The polymer of embodiment 1, wherein the repeating unit has the structure of Formula (I- A):

or an isomer or isotopic variant thereof, wherein R¹ and R³ are as defined in embodiment 1.

3. The polymer of embodiment 1 or 2, wherein R¹ is hydrogen or Ci-Ce alkyl.

4. The polymer of any one of embodiments 1 to 3, wherein R¹ is hydrogen.

5. The polymer of any one of embodiments 1 to 3, wherein R¹ is Ci-Ce alkyl.

6. The polymer of embodiment 5, wherein R¹ is methyl, ethyl, or w-propyl.

7. The polymer of embodiment 6, wherein R¹ is methyl.

8. The polymer of any one of embodiments 1 to 7, wherein R³ is methyl.

9. The polymer of embodiment 1, wherein the polymer comprises terminal substituents independently selected from the group consisting of

wherein R¹, R², and R³ are as defined for embodiment 1

10. The polymer of any one of embodiments 1 to 4 and 8 to 9, wherein the repeating unit has the structure of Formula (I-A-i):

or an isotopic variant thereof.

11. The polymer of any one of embodiments 1 to 10, wherein the polymer comprises 15 to 149 repeating units.

12. A polymer comprising 15 to 149 repeating units, wherein each repeating unit has the structure of Formula (I-A-i):

and wherein the polymer further comprises terminal substituents independently selected from the group consisting of:

13. A copolymer compri sing :

(i) a first polymer, wherein said first polymer is the polymer of any one of embodiments 1 to 12; and

(ii) one or more additional polymer(s), wherein said one or more additional polymer(s) is/are independently a polystyrene, polyacrylate, polyacrylonitrile, polymaleimide, or polymaleic anhydride; wherein the first polymer and the one or more additional polymers(s) are structurally different. 14. The copolymer of embodiment 13, wherein the copolymer is a block copolymer, random copolymer, or alternating copolymer.

15. The copolymer of embodiment 13 or 14, wherein the first polymer is the polymer of any one of embodiments 10 to 12.

16. The copolymer of any one of embodiments 13 to 15, wherein the one or more additional polymer(s) comprise(s) a repeating unit, wherein the repeating unit has the structure of Formula (II):

or an isotopic variant thereof.

17. The copolymer of embodiment 16, wherein the one or more additional polymer(s) comprise(s) 10 to 150 repeating units.

18. The copolymer of embodiment 16 or 17, wherein the copolymer further comprises, where chemically permissible, terminal substituents independently selected from the group consisting of:

19. A copolymer compri sing :

(i) a first polymer, wherein said first polymer comprises 5 to 75 repeating units having the structure of Formula (I-A-i):

or an isotopic variant thereof; and

(ii) one additional polymer, wherein said one additional polymer comprises 10 to 150 repeating units having the structure of Formula (II):

wherein the first polymer and the one or more additional polymers(s) are structurally different, and the copolymer further comprises, where chemically permissible, terminal substituents independently selected from the group consisting of:

20. A composition comprising the polymer of any one of embodiments 1 to 12, or the copolymer of any one of embodiments 13 to 19, and an acceptable carrier.

21. The composition of embodiment 20, wherein the composition is formulated for topical administration.

22. The composition of embodiment 20 or 21, wherein the composition is in the form of a topical lotion, an oil, a spray, a lip balm, or a make-up cream.

23. A method of protecting a keratinous substrate from ultraviolet radiation comprising applying the polymer of any one of embodiments 1 to 12, the copolymer of any one of embodiments 13 to 19, or the composition of any one of embodiments 20 to 22 to a keratinous substrate of a subject in need thereof. 24. The method of embodiment 23, wherein the keratinous substrate is skin, hair, scalp, or nails.

25. A method of protecting skin from ultraviol ent radiation comprising applying the polymer of any one of embodiments 1 to 12, the copolymer of any one of embodiments 13 to 19, or the composition of any one of embodiments 20 to 22 to skin of a subject in need thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 provides the proton nuclear magnetic resonance (^XH NMR) spectrum for Polymer 1. ¹ H NMR (500 MHz, CDC1₃) peaks appear at 5 7.97 - 7.93 (d), 7.78 - 7.49 (br),

6.97 - 6.91 (d), 6.59 - 6.46 (br), 6.46 - 6.28 (br), 4.03 - 3.74 (m), 2.56 (s), 1.84 - 0.97 (m), and 0.90 - 0.81 (m) ppm. Solvent residual peaks also appear at 7.26 (CHCI3) and 1.60 (H2O) ppm.

[0013] FIG. 2 provides the dynamic light scattering (DLS) spectrum for Polymer 1.

[0014] FIG. 3 provides the ultraviolet-visible spectroscopy (UV-Vis) spectrum for Polymer 1.

[0015] FIG. 4 provides the 'H NMR spectrum for Copolymer 2. 'H NMR (500 MHz, CDCI3) peaks appear at 5 7.97 - 7.91 (d), 7.82 - 7.48 (br), 7.21 - 6.83 (br), 6.63 - 6.27 (br),

3.97 - 3.84 (m), 2.56 (s), 1.88 - 1.59 (br), 1.53 (s), 1.49 - 1.19 (br) ppm. Solvent residual peaks also appear at 7.26 (CHCI3) and 1.69 (H2O) ppm.

[0016] FIG. 5 provides the DLS spectrum for Copolymer 2.

[0017] FIG. 6 provides the UV-Vis spectrum for Copolymer 2.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0018] The present disclosure provides polymers and copolymers, as well as compositions thereof, that absorb and/or scatter ultraviolet light and methods of using such polymers, copolymers, and compositions and methods to protect keratinous substrates, such as skin, from ultraviolet radiation. Such protection from UV radiation reduces the risk of cancer, such as skin cancer, and also prevents premature skin aging, such as wrinkles and age spots. [0019] Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. In case of conflict, the present specification, including definitions, will control. [0020] It should be understood that any of the embodiments described herein, including those described under different aspects of the disclosure and different parts of the specification (including embodiments described only in the Examples) can be combined with one or more other embodiments of this disclosure, unless explicitly disclaimed or improper. Combinations of embodiments are not limited to those specific combinations recited in the claims, including the dependent claims.

[0021] All of the publications, patents and published patent applications referred to in this application are specifically incorporated by reference in their entirety. In case of conflict, the present specification, including its specific definitions, will control.

[0022] Where aspects or embodiments are described in terms of a Markush group or other grouping of alternatives, the present application encompasses not only the entire group listed as a whole, but each member of the group individually and all possible subgroups of the main group, and also the main group absent one or more of the group members.

[0023] Throughout this specification, the word “comprise” or variations such as “comprises” or “comprising” will be understood to imply the inclusion of a stated integer (or components) or group of integers (or components), but not the exclusion of any other integer (or components) or group of integers (or components).

[0024] Throughout the specification, where compositions are described as having, including, or comprising (or variations thereof), specific components, it is contemplated that compositions also may consist essentially of, or consist of, the recited components.

Similarly, where methods or processes are described as having, including, or comprising specific process steps, the processes also may consist essentially of, or consist of, the recited processing steps. Further, it should be understood that the order of steps or order for performing certain actions is immaterial so long as the compositions and methods described herein remains operable. Moreover, two or more steps or actions can be conducted simultaneously.

[0025] The term “consisting of’ excludes any element, step, or ingredient not specifically recited.

[0026] The term “consisting essentially of’ limits the scope of a disclosure to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s) of the disclosure. [0027] The term “including,” as used herein, means “including but not limited to.” “Including” and “including but not limited to” are used interchangeably. Thus, these terms will be understood to imply the inclusion of a stated integer (or components) or group of integers (or components), but not the exclusion of any other integer (or components) or group of integers (or components).

[0028] Any example(s) following the term “e.g.,” or “for example” is not meant to be exhaustive or limiting.

[0029] Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0030] The articles “a,” “an” and “the” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article.

[0031] When a range of values is listed, it is intended to encompass each value and subrange within the range. For example, “Ci-Ce alkyl” is intended to encompass, Ci, C2, C3, C4, C₅, C₆, Ci-C₆, C1-C5, C1-C4, C1-C3, C1-C2, C₂-C₆, C2-C5, C2-C4, C2-C3, C₃-C₆, C3-C5, C3-C4, C₄-C₆, C4-C5, and C₅-C₆ alkyl.

DEFINITIONS

[0032] In order that the disclosure may be more readily understood, certain terms are first defined. These definitions should be read in light of the remainder of the disclosure, as understood by a person of ordinary skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art.

[0033] Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 102^nd Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Clayden, Greeves, and Warren, Organic Chemistry, 2^nd Edition, Oxford University Press, Oxford, 2012; Smith and March, March ’s Advanced Organic Chemistry, 8^th Edition, John Wiley & Sons, Inc., New Jersey, 2020; Larock, Comprehensive Organic Transformations, 3^rd Edition, John Wiley & Sons, Inc., New Jersey, 2018; Kurti and Czako, Strategic Applications of Named Reactions in Organic Synthesis, Elsevier, Inc., 2005; Carruthers & Coldham, Modern Methods of Organic Synthesis, 4^th Edition, Cambridge University Press, Cambridge, 2004; and Vogel and Houk, Organic Chemistry: Theory, Reactivity and Mechanisms in Modern Synthesis, 1^st Edition, Wiley-VCH, Weinheim, 2019. [0034] It should be understood that the terms “groups” and “radicals” can be considered interchangeable when used herein.

[0035] It should also be understood that the terms “macromolecule” and “polymer” can be considered interchangeable when used herein and refer to a molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived from molecules of low relative molecular mass. Additionally, the term “polymer,” as used herein, refers to homopolymers derived from a single type/species of monomer, whereas “copolymer” is intended to refer to a polymer derived from two or more different types/species of monomers.

[0036] “Alkoxy” refers to the group -OR, wherein R is an alkyl group as defined herein. In some embodiments, an alkoxy group has 1 to 6 carbon atoms (“Ci-Ce alkoxy”). In some embodiments, an alkoxy group has 1 to 3 carbon atoms (“C1-C3 alkoxy”). Examples of Ci-Ce alkoxy groups include, but are not limited to, methoxy (Ci), ethoxy (C2), //-propoxy (C3), i- propoxy (C3), //-butoxy (C4), z-butoxy (C4), .scc-butoxy (C4), and tert-butoxy (C4).

[0037] “Alkyl” refers to a radical of a straight-chain i.e., linear) or branched saturated hydrocarbon group. In some embodiments, an alkyl group has from 1 to 6 carbon atoms (“Ci-Ce alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C1-C5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C1-C4 alkyl”). In some embodiments, an alkyl group has 3 to 5 carbon atoms (“C3-C5 alkyl”). In some embodiments, an alkyl group has 4 carbon atoms (“C4 alkyl”). Examples of Ci-Ce alkyl groups include, but are not limited to, methyl (Ci), ethyl (C2), //-propyl (C3), z-propyl (C3), n- butyl (C4), z-butyl (C4), sec-butyl (C4), and tert-butyl (C4). Unless otherwise specified, each instance of an alkyl group is independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents, e.g., from 1 to 4 substituents, 1 to 3 substituents, or 1 substituent. In some embodiments, the substituents are independently selected from the group consisting of halogen (i.e., fluoro, chloro, bromo, or iodo), -CN, -NO2, -OH, -NH2, and Ci-Ce alkoxy.

[0038] As used herein, the terms “applying” and “application” include any suitable route for providing a keratinous substrate, such as skin, with the polymers, copolymers, or compositions of the disclosure for protection against UV radiation. For example, the polymer, copolymer, or composition may be administered topically. Forms useful in the methods of this disclosure may include lotions, oils, sprays, balms, creams, and the like. Application can also be performed, for example, once, a plurality of times, and/or over one or more extended periods.

[0039] “Cosmetically acceptable” means that the item in question is compatible with a keratinous substrate. For example, “cosmetically acceptable carrier,” refers to compositions, carriers, diluents, and reagents which are compatible with application to a keratinous substrate such as skin, hair, scalp, or nails. The polymers described herein can be mixed with excipients which are cosmetically acceptable, compatible with the active ingredient, and in amounts suitable for the uses described herein. Non-limiting examples of cosmetically acceptable carriers include glycerin, alcohols, organic solvents, fatty alcohols, fatty ethers, fatty esters, polyols, glycols, vegetable oils, mineral oils, liposomes, laminar lipid materials, water, and combinations thereof. Suitable cosmetically acceptable carriers are well known in the art. See, e.g., The International Cosmetic Ingredient Dictionary and Handbook, 16^th Edition, 2016, Nikitakis, J. and Lange, B. Eds., Personal Care Products Council, Washington D C.

[0040] “Pharmaceutically acceptable” means approved or approvable by a regulatory agency of the Federal or a state government or the corresponding agency in countries other than the United States, or that is listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly, in humans.

[0041] “Pharmaceutically acceptable carrier” refers to compositions, carriers, diluents, and reagents which are pharmaceutically acceptable materials that are compatible with administration to or application upon a subject. The polymers described herein can be mixed with excipients which are pharmaceutically acceptable, compatible with the active ingredient, and in amounts suitable for the uses described herein. Non-limiting examples of suitable pharmaceutically acceptable carriers include water, saline, dextrose, glycerol, ethanol or the like and combinations thereof. Suitable carriers and their formulations are described, for example, in Remington’s Pharmaceutical Sciences by E. W. Martin.

[0042] The terms “subject” and “individual” are used interchangeably herein and refer to a human. In some embodiments, the subject is or will be exposed to UV radiation. The UV radiation may come from sunlight. Alternatively, the UV radiation can come from an artificial source. A “subject in need thereof’ is a subject in need of protection from UV radiation.

[0043] The term “sunscreen composition,” as used herein, refers to compositions that are intended for exterior bodily use to provide protection against ultraviolet radiation. A sunscreen composition may, for example, be used to confer a healthy and/or cosmetic benefit to its users. Non-limiting examples of sunscreen compositions include a tanning lotion, a sunscreen, and a sunblock.

[0044] Polymers or copolymers that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers.” Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers.” Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers.” When a polymer or copolymer has one asymmetric center, a pair of enantiomers is possible. Such polymers or copolymers can exist as either an individual enantiomer or as a mixture of both possible enantiomers. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. When a polymer or copolymer has two or more asymmetric centers, multiple diastereomers are possible. Such polymers or copolymers can exist as either an individual diastereomer or as a mixture of two or more possible diastereomers and, thus, may be characterized by varying tacti cities (i.e., relative orderliness of the succession of configurationally defined repeating units in the main chain (backbone) of the polymer or copolymer).

POLYMERS OF THE DISCLOSURE

[0045] In a first aspect, the disclosure provides a polymer that absorbs and/or scatters ultraviolet light. Consequently, the polymers of the disclosure are contemplated as useful at least for protecting a keratinous substrate, such as skin, from ultraviolet radiation.

[0046] In some embodiments, the polymer is a polystyrene, polyacrylate, polyacrylonitrile, polymaleimide, or polymaleic anhydride. In some embodiments, the polymer comprises a repeating unit, wherein the repeating unit has the structure of Formula (I):

or an isomer or isotopic variant thereof, wherein:

R¹ is hydrogen, Ci-C₆ alkyl, -C(O)OH, -C(O)O(Ci-C₆ alkyl), or -CN;

R² is hydrogen or Ci-Ce alkyl; or R¹ and R², together with the carbon atoms to which they are attached, form a pyrrolidine-2, 5-dione or dihydrofuran-2, 5-dione; and

R³ is Ci-Ce alkyl.

In some embodiments, the isomer of Formula (I) is an enantiomer or a diastereomer thereof. In some embodiments, the repeating unit has the structure of Formula (I), as defined herein, or an isotopic variant thereof. In some embodiments, the repeating unit has the structure of Formula (I), as defined herein.

[0047] In some embodiments, the repeating unit has the structure of Formula (I- A):

or an isomer or isotopic variant thereof, wherein R¹ and R³ are as defined for Formula (I). In some embodiments, the isomer of Formula (I- A) is an enantiomer or a diastereomer thereof. In some embodiments, the repeating unit has the structure of Formula (I- A), as defined herein, or an isotopic variant thereof. In some embodiments, the repeating unit has the structure of Formula (I- A), as defined herein.

[0048] In some embodiments, the repeating unit has the structure of Formula (I-A-i):

or an isotopic variant thereof. In some embodiments, the repeating unit has the structure of Formula (I-A-i), as defined herein.

[0049] In some embodiments, R¹ is hydrogen, Ci-Ce alkyl, -C(O)OH, -C(O)O(Ci-Ce alkyl), or -CN. In some embodiments, R¹ is hydrogen or Ci-Ce alkyl. In some embodiments, R¹ is hydrogen or C1-C3 alkyl. In some embodiments, R¹ is hydrogen. In some embodiments, R¹ is Ci-Ce alkyl. In some embodiments, R¹ is C1-C3 alkyl. In some embodiments, R¹ is methyl, ethyl, or w-propyl. In some embodiments, R¹ is methyl. [0050] In some embodiments, R² is hydrogen or Ci-Ce alkyl. In some embodiments, R² is hydrogen or C1-C3 alkyl. In some embodiments, R² is hydrogen. In some embodiments, R² is Ci-Ce alkyl. In some embodiments, R² is C1-C3 alkyl. In some embodiments, R² is methyl, ethyl, or w-propyl. In some embodiments, R² is methyl.

[0051] In some embodiments, R¹ and R², together with the carbon atoms to which they are attached, form a pyrrolidine-2, 5-dione or dihydrofuran-2, 5-dione. In some embodiments, R¹ and R², together with the carbon atoms to which they are attached, form a pyrrolidine-2, 5- dione. In some embodiments, R¹ and R², together with the carbon atoms to which they are attached, form a dihydrofuran-2, 5-dione.

[0052] In some embodiments, R³ is Ci-Ce alkyl. In some embodiments, R³ is C1-C3 alkyl. In some embodiments, R³ is methyl, ethyl, or w-propyl. In some embodiments, R³ is methyl. [0053] In some embodiments, the polymer comprises 15 to 149 repeating units. In some embodiments, the polymer comprises 25 to 139 repeating units. In some embodiments, the polymer comprises 35 to 129 repeating units. In some embodiments, the polymer comprises 45 to 119 repeating units. In some embodiments, the polymer comprises 55 to 109 repeating units. In some embodiments, the polymer comprises 65 to 99 repeating units. In some embodiments, the polymer comprises 75 to 89 repeating units. In some embodiments, the polymer comprises 80 to 84 repeating units. In some embodiments, the polymer comprises 82 repeating units.

[0054] As will be appreciated by the skilled worker, polymers of the disclosure are generally obtained as heterogenous mixtures of polymers characterized by different lengths (i.e., varying numbers of repeating units) and comprising various terminal substituents. Appropriate terminal substituents for the polymers described herein will be apparent to or readily deduced by one of ordinary skill in the art. For example, in some embodiments, the polymer comprises, where chemically permissible, terminal substituents independently selected from the group consisting of:

, wherein R¹, R², and R³ are as defined for

Formula (I). [0055] In some embodiments, the polymer comprises 15 to 149 repeating units having the structure of Formula (I-A-i):

and further comprises, where chemically permissible, terminal substituents independently selected from the group consisting of:

[0056] As one of skill in the art will recognize, polymers of the present disclosure (e.g., those comprising R¹, R², and/or R³ Ci-Ce alkyl groups) can comprise one or more asymmetric carbon atoms, and thus can exist in various isomeric forms, e.g., enantiomers and/or diastereomers, and be characterized by varying tacti cities (i.e., relative orderliness of the succession of configurationally defined repeating units in the main chain (backbone) of the polymer). For example, the polymers described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Accordingly, also contemplated herein are polymers as described herein as individual stereoisomers substantially free of other stereoisomers, and alternatively, as mixtures of various stereoisomers. It is known in the art that the tacticity of a polymer can be controlled during synthesis.

[0057] Polymers described herein may also comprise one or more isotopic substitutions. For example, H may be in any isotopic form, including ¹H, ²H (D or deuterium), and ³H (T or tritium); C may be in any isotopic form, including ¹²C, ¹³C, and ¹⁴C; O may be in any isotopic form, including ¹⁶O and ¹⁸O; and the like. Accordingly, also contemplated herein are “isotopic variants” of the polymers of the disclosure, which are identical to those recited in Formulae (I), (I-A), or (I-A-i), as defined herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature.

COPOLYMERS OF THE DISCLOSURE

[0058] In a second aspect, the disclosure provides a copolymer that absorbs and/or scatters ultraviolet light. Consequently, the copolymers of the disclosure are contemplated as useful at least for protecting a keratinous substrate, such as skin, from ultraviolet radiation.

[0059] In some embodiments, the copolymer comprises: (i) a first polymer, wherein said first polymer is a polymer of the disclosure; and (ii) one or more additional polymer(s), wherein said one or more additional polymer(s) is/are independently a polystyrene, polyacrylate, polyacrylonitrile, polymaleimide, or polymaleic anhydride; wherein the first polymer and the one or more additional polymer(s) are structurally different.

[0060] In some embodiments, the copolymer is a block copolymer, random copolymer, or alternating copolymer. In some embodiments, the copolymer is a block copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the copolymer is an alternating copolymer.

[0061] In some embodiments, the first polymer comprises a repeating unit, wherein the repeating unit has the structure of Formula (I), as defined herein, or an isotopic variant thereof. In some embodiments, the first polymer comprises a repeating unit, wherein the repeating unit has the structure of Formula (I- A), as defined herein, or an isotopic variant thereof. In some embodiments, the first polymer comprises a repeating unit, wherein the repeating unit has the structure of Formula (I-A-i), as defined herein, or an isotopic variant thereof. In some embodiments, the first polymer comprises 5 to 75 repeating units having the structure of Formula (I-A-i), as defined herein, or an isotopic variant thereof. In some embodiments, the first polymer comprises 40 repeating units having the structure of Formula (I-A-i), as defined herein, or an isotopic variant thereof.

[0062] In some embodiments, the one or more additional polymer(s) is/are independently a polystyrene, polyacrylate, polyacrylonitrile, polymaleimide, or polymaleic anhydride. In some embodiments, the one or more additional polymer(s) is/are independently an unsubstituted polystyrene, unsubstituted polyacrylate, unsubstituted polyacrylonitrile, unsubstituted polymaleimide, or unsubstituted polymaleic anhydride. In some embodiments, the one or more additional polymer(s) is/are independently a polymaleimide or polymaleic anhydride. In some embodiments, the one or more additional polymer(s) is/are independently an unsubstituted polymaleimide or unsubstituted polymaleic anhydride. In some embodiments, the one or more additional polymer(s) is/are independently a polystyrene, polyacrylate, or polyacrylonitrile. In some embodiments, the one or more additional polymer(s) is/are independently an unsubstituted polystyrene, unsubstituted polyacrylate, or unsubstituted polyacrylonitrile. In some embodiments, the one or more additional polymer(s) is/are independently a polystyrene or polyacrylate. In some embodiments, the one or more additional polymer(s) is/are independently an unsubstituted polystyrene or unsubstituted polyacrylate. In some embodiments, the one or more additional polymer(s) is/are independently a polystyrene. In some embodiments, the one or more additional polymer(s) is/are independently an unsubstituted polystyrene. In some embodiments, the one or more additional polymer(s) comprise(s) a repeating unit, wherein the repeating unit has the structure of Formula (II):

or an isotopic variant thereof. In some embodiments, the one or more additional polymer(s) comprise(s) 10 to 150 repeating units having the structure of Formula (II), as defined herein, or an isotopic variant thereof.

[0063] In some embodiments, the copolymer comprises: (i) a first polymer, wherein said first polymer comprises 5 to 75 repeating units having the structure of Formula (I-A-i), as defined herein, or an isotopic variant thereof; and (ii) one additional polymer, wherein said one additional polymer comprises 10 to 150 repeating units having the structure of Formula (II), as defined herein, or an isotopic variant thereof.

[0064] As will be appreciated by the skilled worker, copolymers of the disclosure are generally obtained as heterogenous mixtures of copolymers characterized by different lengths (i.e., varying numbers of repeating units in the first polymer and one or more additional polymer(s)) and comprising various terminal substituents. Appropriate terminal substituents for the copolymers described herein will be apparent to or readily deduced by one of ordinary skill in the art. For example, in some embodiments, the copolymer comprises: (i) a first polymer, wherein said first polymer comprises 5 to 75 repeating units having the structure of Formula (I-A-i), as defined herein, or an isotopic variant thereof; and (ii) one additional polymer, wherein said one additional polymer comprises 10 to 150 repeating units having the structure of Formula (II), as defined herein, or an isotopic variant thereof; and further comprises, where chemically permissible, terminal substituents independently selected from the group consisting of:

[0065] As one of skill in the art will recognize, copolymers of the present disclosure (e.g., those comprising R¹, R², and/or R³ Ci-Ce alkyl groups) can comprise one or more asymmetric carbon atoms, and thus can exist in various isomeric forms, e.g., enantiomers and/or diastereomers, and can be characterized by varying tacti cities (i.e., relative orderliness of the succession of configurationally defined repeating units in the main chain (backbone) of the copolymer). For example, the copolymers described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Accordingly, also contemplated herein are copolymers as described herein as individual stereoisomers substantially free of other stereoisomers, and alternatively, as mixtures of various stereoisomers. It is known in the art that the tacticity of a copolymer can be controlled during synthesis.

[0066] Copolymers described herein may also comprise one or more isotopic substitutions. For example, H may be in any isotopic form, including ¹H, ²H (D or deuterium), and ³H (T or tritium); C may be in any isotopic form, including ¹²C, ¹³C, and ¹⁴C; O may be in any isotopic form, including ¹⁶O and ¹⁸O; and the like. Accordingly, also contemplated herein are “isotopic variants” of the copolymers of the disclosure, wherein one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature.

COMPOSITIONS OF THE DISCLOSURE

[0067] In a third aspect, the present disclosure provides a composition that absorbs and/or scatters ultraviolet light and, accordingly, is contemplated as useful at least for protecting a keratinous substrate from ultraviolet radiation. In some embodiments, the disclosure provides a composition comprising a polymer or copolymer disclosed herein and an acceptable carrier. In some embodiments, the disclosure provides a composition comprising a polymer disclosed herein and an acceptable carrier. In some embodiments, the disclosure provides a cosmetic composition comprising a copolymer disclosed herein and an acceptable carrier. In some embodiments, the carrier is suitable for topical administration to a keratinous substrate. In some embodiments, the carrier is a cosmetically acceptable carrier. Suitable cosmetically acceptable carriers are well known in the art. See, e.g., The International Cosmetic Ingredient Dictionary and Handbook, 16^th Edition, 2016, Nikitakis, J. and Lange, B. Eds., Personal Care Products Council, Washington D.C. In some embodiments, the carrier is a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers are well-known in the art. See, e.g., Remington’s Pharmaceutical Sciences by E. W. Martin. In some embodiments, the pharmaceutically acceptable carrier is formulated for topical administration.

[0068] The compositions of the present disclosure may be in a variety of forms. The preferred form depends on the intended mode of application, and may take such forms as dispersions (e.g., nonionic vesicle dispersions), creams, milks, lotions, gels, cream gels, ointments, oils, foams, sprays, aerosols, aerosol foams (e.g., mousses), balms, serums, powders, solids, sticks/pencils, suspensions, solutions, or emulsions in oily or aqueous carriers. For example, in some embodiments, the composition is in the form of a lotion, an oil, a spray, a lip balm, or a make-up cream. In some embodiments, the composition is formulated for topical application. In some embodiments, the composition is a sunscreen composition. Non-limiting examples of compositions include such products as moisturizers, cleansers, conditioners, shampoo, body wash, styling gel/lotion, eye cream and eye liner, blush, mascara, foundation, nail polish, polish remover, eye shadow, lipstick, lip gloss, lip liners, lip balms, makeup remover, nail treatment, foot care compositions, acne treatment, redness/rosacea treatment, varicose/spider vein treatment, anti-aging compositions, sunless tanning compositions, after-sun compositions, concealers, hair color and bleaching compositions, skin fading/lighteners, body firming lotion, shaving cream, after shave, relaxer, antiperspirants and deodorants, exfoliants, scrubs, liquid hand soap, bubble bath, pain and wound treatment compositions, insect repellant, anti-itch and rash cream, styling mousse and foams, perfume, lubricants, body oil, body spray, baby lotion, diaper cream, baby soap, baby shampoo, baby oil, baby wipes, hair-loss treatment, hair spray, depilatory, hair growth inhibitors, hair removal waxes, personal cleansing, cologne, oil controller, and hand sanitizer. [0069] In some embodiments, the composition is in the form of an aerosol, wherein the composition is combined with at least one propellant, which may be any suitable gas that can be compressed or liquefied within a spray dispensing canister and which expands or volatilizes to vapor or gas form upon exposure to ambient temperature and pressure conditions to deliver the composition in an aerosol form. Suitable propellants are known in the art. Non-limiting examples of propellants include methane, ethane, propane, isopropane, butane, isobutane, butene, pentane, isopentane, neopentane, pentene, hydrofluorocarbons (HFCs), chlorofluorocarbons (CFCs), nitrogen, ethers including dimethyl ether, and any mixtures thereof. The skilled artisan would recognize that in a closed container propellants such as dimethyl ether condense to the liquid state at ambient temperature. Thus, the composition in the aerosol container is liquid formulation containing a mixture of dissolved propellant, undissolved liquid propellant, and gaseous propellant, under pressure due to the vapor pressure of the propellant.

[0070] The compositions of the present disclosure comprise an acceptable carrier. Preferably, acceptable carriers are suitable for application to a keratinous substrate, have good aesthetic properties, are compatible with the polymers of the present disclosure and any other components in the described compositions, and do not cause any safety or toxicity concerns. The carriers may themselves be in a wider variety of forms. For example, carriers may be in the form of oil-in-water or water-in-oil emulsions. Oil-in-water and water-in-oil emulsions are known in the art. See, e.g., U.S. Patent Publication No. 2005/0019356, the entirety of which is incorporated herein by reference. Oil-in-water emulsion refers to an emulsion having a continuous aqueous phase and a hydrophobic, water-insoluble phase (“oil phase”) dispersed therein. Water-in-oil emulsion refers to emulsion having a continuous hydrophobic, water insoluble oil phase and a water phase dispersed therein. Such emulsions often comprise an emulsifier which helps disperse and suspend the aqueous phase within the oil and/or silicone layer. Emulsifiers are well known in the art, and include nonionic, anionic, cationic, and amphoteric variants. The “oil phase” of either an oil-in-water emulsion or a water-in-oil emulsion can contain oil, silicone or mixtures thereof. The water phase of these emulsions consists primarily of water but can also contain various other ingredients such as thickeners, acids, bases, salts, chelants, gums, water-soluble or dispersible alcohols and polyols, buffers, preservatives, colorings, and the like.

[0071] The compositions of the present disclosure may comprise additional components beyond those specified herein. Suitable additional components will be readily ascertainable by the skilled artisan and should, when incorporated into the composition, be suitable for application to a keratinous substrate without undue toxicity, incompatibility, instability, allergic response, and the like within the scope of sound judgement. The International Cosmetic Ingredient Dictionary and Handbook, 16^th Edition, 2016, Nikitakis, J. and Lange, B. Eds., Personal Care Products Council, Washington D.C. describes a wide variety of nonlimiting ingredients commonly used in the skin care industry, which are suitable for use in the compositions of the present disclosure. Examples of these ingredient classes include: abrasives, absorbents, fragrances, pigments, colorings/colorants, essential oils, skin sensates, astringents, antiacne agents, anticaking agents, antifoaming agents, antimicrobial agents, antioxidants, binders, buffering agents, bulking agents, chelating agents, cosmetic biocides, denaturants, external analgesics, film formers or materials, opacifying agents, pH adjusters, plasticizers, propellants, reducing agents, sequestrants, skin bleaching and lightening agents, skin-conditioning agents, skin soothing and/or healing agents and derivatives, skin treating agents, thickeners, UV light absorbers or filters, SPF boosters, solvents, waterproofing agents, and vitamins and derivatives thereof. In some embodiments, the compositions of the present disclosure may comprise desquamation actives, anti-acne actives, anti-wrinkle/anti- atrophy actives, anti-oxidants/racial scavengers, chelators, flavonoids, anti-inflammatory agents, anti-cellulite agents, tanning actives, skin lightening agents, antimicrobial and antifungal actives, conditional agents, thickening agents, and/or water-soluble vitamins. [0072] The compositions of the present disclosure may comprise an acceptable emollient. As used herein, “emollient” refers to a material useful for the prevention or relief of dryness, as well as for the protection of keratinous substrates. Typically, emollients are oleaginous or oily substances which help to smooth and soften a keratinous substrate, and may also reduce its roughness, cracking, or irritation. Non-limiting examples of suitable emollients include mineral oil, lanolin oil, coconut oil, cocoa butter, olive oil, almond oil, macadamia nut oil, aloe extracts, synthetic jojoba oils, natural Sonora jojoba oils, safflower oil, com oil, liquid lanolin, cotton seed oil, and peanut oil.

[0073] The compositions may incorporate ingredients that enhance their UV light absorbing and/or scattering properties. For example, the described compositions may optionally comprise additional organic and/or inorganic UV light filtering agents. Non-limiting examples of such additional filtering agents include para aminobenzoic acid, avobenzone, cinoxate, dioxybenzone, homosalate, menthyl anthranilate, octyl salicylate, oxybenzone, padimate O, phenylbenzimidazole sulfonic acid, sulisobenzone, trolamine salicylate, titanium dioxide, zinc oxide, iron oxide, zirconium oxide, cerium oxide, diethanolamine methoxycinnamate, digalloy trioleate, ethyl dihydroxypropyl PABA, glyceryl aminobenzoate, lawsone with dihydroxyacetone, red petrolatum, ethylhexyl triazone, dioctyl butamido triazone, benzylidene malonate polysiloxane, terephthalylidene dicamphor sulfonic acid, disodium phenyl dibenzimidazole tetrasulfonate, diethylamino hydroxybenzoyl hexyl benzoate, bis diethylamino hydroxybenzoyl benzoate, bis benzoxazoylphenyl ethylhexylimino triazine, drometrizole trisiloxane, methylene bis-benzotriazolyl tetramethylbutylphenol, and bis-ethylhexyloxyphenol methoxyphenyltriazine, 4- methylbenzylidenecamphor, and isopentyl 4-methoxycinnamate. In some embodiments, the additional filtering agent is selected from the group consisting of titanium dioxide, zinc oxide, iron oxide, zirconium oxide, cerium oxide, UV light filtering polymers beyond those disclosed herein, and mixtures thereof.

METHODS OF USE

[0074] In a fourth aspect, the present disclosure provides a method of protecting a keratinous substrate from ultraviolet radiation. In some embodiments, the method comprises applying a polymer, copolymer, or composition of the disclosure to a keratinous substrate of a subject in need thereof. In some embodiments, the polymer or copolymer is applied directly to a keratinous substrate. In some embodiments, the polymer or copolymer is applied as a composition disclosed herein. In some embodiments, the keratinous substrate is skin, hair, scalp, or nails. In some embodiments, the keratinous substrate is skin. In some embodiments, the polymer, copolymer, or composition is applied topically.

[0075] A fifth aspect of the present disclosure provides a method of protecting skin from ultraviolet radiation. In some embodiments, the method comprises applying a polymer, copolymer, or composition of the disclosure to the skin of a subject in need thereof. In some embodiments, the polymer or copolymer is applied directly to the skin. In some embodiments, the polymer or copolymer is applied as a composition disclosed herein. In some embodiments, the polymer, copolymer, or composition is applied topically.

EXAMPLES

[0076] Exemplary methods and materials are described herein, although methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the various aspects and embodiments of the disclosure. The materials, methods, and examples are illustrative only and not intended to be limiting.

[0077] The polymers and copolymers provided herein can be prepared from readily available starting materials using the following general methods and procedures. It will be appreciated that where typical or preferred process conditions (i.e., reaction temperatures, times, mole ratios of reactants, solvents, pressures, etc.) are given, other process conditions can also be used unless otherwise stated. Optimum reaction conditions may vary with the particular reactants or solvent used, but such conditions can be determined by one skilled in the art through routine optimization.

Chemical Abbreviations

[0078] AIBN: azobisisobutyronitrile; HC1: hydrogen chloride / hydrochloric acid; MeOH: methanol; NaH: sodium hydride; PhMe: toluene; THF: tetrahydrofuran.

EXAMPLE 1 : Synthesis of Polymer 1

[0079] Synthesis of Intermediate 1.2

[0080] 1.1 (1 g, 6.2 mmol) and AIBN (10 mg, 0.06 mmol) were dissolved in PhMe (2 mL).

The resulting mixture was then subjected to three freeze-pump-thaw cycles. Then, the mixture was heated to 65 °C and stirred for 24 h. The solution was cooled to room temperature and poured into MeOH. The resulting white solid was filtered and dried in vacuo to afford 1.2 (0.53 g, 53%).

[0081] Synthesis of Polymer 1

[0082] 1.2 (0.1 g) and NaH (0.030 g, 1.24 mmol) were dissolved in dry THF (1 mL). A solution of 1.3 (0.093 g, 0.62 mmol) in dry THF (1 mL) was added dropwise. The reaction mixture was then stirred while refluxing for 4 h. After being cooled to room temperature, the reaction mixture was poured into ice water (20 mL) and adjusted to pH ~6 by addition of HC1. The resulting yellow solid was filtered and dried in vacuo to afford Polymer 1 (0.11 g, 57%), which comprises a repeating unit having the structure of Formula (LA-i).

[0083] The ¹ H NMR spectrum of Polymer 1 was obtained in CDChusing an AVANCE III HD500 available from Bruker. See, Fig. 1.

[0084] The DLS spectrum for Polymer 1 was obtained using a Litesizer 500 Particle Analyzer available from Anton Parr. Polymer 1 was analyzed at a concentration of 2 mg/mL in THF applied to a quartz cuvette at room temperature. DLS: M_n = 23,100; M_w/M_n = 1.67; D = 0.27; D50 = 12.3 nm. See, Fig. 2. [0085] The UV-Vis spectrum for Polymer 1 was obtained using an Agilent Cary 5000 UV- Vis available from Agilent. Polymer 1 was analyzed in the 250-800 nm range at a concentration of 10 mg/mL applied to a 1 x 1 in² quartz sheet. See, Fig. 3. The UV-Vis spectrum was normalized to baseline.

EXAMPLE 2: Synthesis and Analysis of Copolymer 2

[0086] Synthesis of Intermediate 2.2

[0087] 1.1 (1.31 g, 8.1 mmol) and 2.1 (1.69 g, 16.2 mmol) were dissolved in PhMe (10 mL). The resulting mixture was then subjected to three freeze-pump-thaw cycles. Then, AIBN (0.030 g, 0.18 mmol) was added and the mixture was heated to 65 °C and stirred overnight. The mixture was cooled to room temperature and poured into MeOH. The resulting solid was filtered and dried in vacuo to afford 2.2.

[0088] Synthesis of Copolymer 2

[0089] 2.2 (0.5 g) and NaH (0.065 g, 2.7 mmol) were dissolved in THF (5 mL). A solution of 1.3 (0.20 g, 1.35 mmol) in dry THF (2 mL) was added dropwise. The reaction was then stirred while refluxing overnight. After being cooled to room temperature, the reaction mixture was poured into ice water (150 mL) and adjusted to pH ~ 6 by addition of HC1. The resulting yellow solid was filtered and dried in vacuo to afford Copolymer 2, which comprises a first repeating unit having the structure of Formula (LA-i) and an additional repeating unity having the structure of Formula (II).

[0090] The ¹ H NMR spectrum of Copolymer 2 was obtained in CDCh using an AVANCE III HD500 available from Bruker. See, Fig. 4.

[0091] The DLS spectrum for Copolymer 2 was obtained using a Litesizer 500 Particle Analyzer available from Anton Parr. Copolymer 2 was analyzed at a concentration of 2 mg/mL in THF applied to a quartz cuvette at room temperature. DLS: M_n = 19,800; M_w/M_n = 1.77; D = 0.24; D50 = 5.4 nm. See, Fig. 5. The UV-Vis spectrum was normalized to baseline.

[0092] The UV-Vis spectrum for Copolymer 2 was obtained using an Agilent Cary 5000 UV-Vis available from Agilent. Copolymer 2 was analyzed in the 250-800 nm range at a concentration of 10 mg/mL applied to a 1 x 1 in² quartz sheet. See, Fig. 6.

EXAMPLE 3 : Skin Permeability Assay

[0093] As described herein, the chemical sunscreen UV filter itself can increase UV- induced ROSs after penetrating the epidermis and contribute to cellular alterations, hormonal disruptions, and carcinogenesis. Accordingly, organic chemical UV filters with low skin permeability are desirable. The following protocols can be used to evaluate the skin permeability of the disclosed polymers and copolymers.

Donor Solution Preparation

[0094] 10 mg/mL donor solutions are prepared according to the following formula:

2 mL donor solution = 73% DI water (1460 pL) + 25% mineral oil (500 pL) + 2% Tween 80 (40 pL) + 20 mg sample

[0095] The donor solutions are prepared according to the following protocol:

1) Mineral oil (500 pL) is added to a 3 mL vial, followed by Tween-80 (40 pL). The polymer analyte (20 mg) is then added to the mixture of mineral oil and Tween- 80. Finally, DI water (1460 pL) is added.

2) The resulting mixture is then homogenized in an ultrasonic bath for 30 min. Diffusion Cell Preparation

[0096] Diffusion cells are prepared for treatment with the donor solution according to the following protocol:

1) A magnetic stirrer is placed into an empty diffusion cell.

2) A Strat M® membrane (artificial skin) is then sandwiched in the middle of the diffusion cell (smooth side facing upward). The diffusion cell is then fixed with clamps after assembly.

3) A 1 x PBS Buffer with 4% BSA solution (7.75 mL) is pipetted into the bottom section of the diffusion cell.

4) The sampling port is then sealed with parafilm to reduce evaportation. Experimental Procedure

[0097] Each tested polymer is assayed in three replicate experiments using different diffusion cells according to the following protocol: 1) Diffusion cells prepared as described herein are warmed in a water bath at 32 °C with stirring at 180 rpm for 10 min.

2) A donor solution (400 pL) prepared as described herein is then added to the top section of each diffusion cell before sealing the injection port with parafilm to reduce evaporation.

3) Samples (500 pL) are collected from the bottom section of each diffusion cell at 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h following addition of the donor solution and are placed into 1.5 mL Eppendorf tubes.

4) The collected volume is then replaced by pipetting a 1 x PBS Buffer with 4% BSA solution (500 pL) into the bottom section of the diffusion cell after each sampling.

Sample Processing

[0098] The collected samples are then processed according to the following protocol:

1) A portion of the sample (200 pL) is transferred to a new 1.5 mL Eppendorf tube and diluted with 95% ethanol (800 pL).

2) The resulting mixture is then vortexed for 15-20 s before being centrifuged for 10 min at 16, 000 rpm.

3) The supernatant obtained from step 2) is then filtered through a 0.22 pM PTFE syringe filter and the filtrate is collected in a 1.5 mL Eppendorf tube.

Data Collection & Analysis

[0099] Prior to analyzing the processed samples obtained from the experiment, calibration of the plate reader is performed according to the following protocol:

1) A 1.0 mg/mL solution of the polymer in DMSO is prepared by first dissolving the polymer (5.0 mg) in DMSO (0.1 mL). That mixture is then diluted with a 1 x PBS Buffer with 4% BSA (4.9 mL). A portion (1.0 mL) of the resulting solution is then removed and used to prepare standard solutions according to the following table (l x PBS buffer with 4% BSA was used as diluent):

Table 1. Preparation of standard solutions for calibration

2) BSA is removed from each of the standard solutions via filtration through a PTFE syringe filter. [0100] Following calibration, each processed sample (200 pL) is pipetted into a microplate well. Absorbance at 320 nm is measured using a plate reader. The results are normalized by subtracting the average absorbance reading of blank (control) replicates from the absorbance readings of the calibration standard solutions and the processed samples.

[0101] A calibration curve is then constructed by plotting the average normalized 320 nm reading for each standard solution (y-axis) vs. its known concentration (ug/ mL; x-axis). The resulting calibration curve is then used to determine the concentration of polymer in the processed samples collected from the experiment. The real permeation rates of the tested polymers are then calculated according to the following formula:

Permeation rate = [(concentration) x (7.75 mL) + S (mass of sample withdrawn)*] / (4 x 10)

*mass of sample withdrawn = (concentration) x (0.5 mL)

Claims

CLAIMS What is claimed is:

or an isomer or isotopic variant thereof, wherein:

R¹ is hydrogen, Ci-C₆ alkyl, -C(O)OH, -C(O)O(Ci-C₆ alkyl), or -CN;

R² is hydrogen or Ci-Ce alkyl; or

R³ is Ci-Ce alkyl.

2. The polymer of claim 1, wherein the repeating unit has the structure of Formula (I-A):

or an isomer or isotopic variant thereof, wherein R¹ and R³ are as defined in claim 1.

3. The polymer of claim 1 or 2, wherein R¹ is hydrogen or Ci-Ce alkyl.

4. The polymer of any one of claims 1 to 3, wherein R¹ is hydrogen.

5. The polymer of any one of claims 1 to 3, wherein R¹ is Ci-Ce alkyl.

6. The polymer of claim 5, wherein R¹ is methyl, ethyl, or w-propyl.

7. The polymer of claim 6, wherein R¹ is methyl.

8. The polymer of any one of claims 1 to 7, wherein R³ is methyl.

9. The polymer of claim 1, wherein the polymer comprises terminal substituents independently selected from the group consisting of

wherein R¹, R², and R³ are as defined for claim 1

10. The polymer of any one of claims 1 to 4 and 8 to 9, wherein the repeating unit has the structure of Formula (I-A-i):

or an isotopic variant thereof.

11. The polymer of any one of claims 1 to 10, wherein the polymer comprises 15 to 149 repeating units.

13. A copolymer compri sing :

(i) a first polymer, wherein said first polymer is the polymer of any one of claims 1 to

12; and

(ii) one or more additional polymer(s), wherein said one or more additional polymer(s) is/are independently a polystyrene, polyacrylate, polyacrylonitrile, polymaleimide, or polymaleic anhydride; wherein the first polymer and the one or more additional polymers(s) are structurally different.

14. The copolymer of claim 13, wherein the copolymer is a block copolymer, random copolymer, or alternating copolymer.

15. The copolymer of claim 13 or 14, wherein the first polymer is the polymer of any one of claims 10 to 12.

16. The copolymer of any one of claims 13 to 15, wherein the one or more additional polymer(s) compri se(s) a repeating unit, wherein the repeating unit has the structure of Formula (II):

or an isotopic variant thereof.

17. The copolymer of claim 16, wherein the one or more additional polymer(s) comprise(s) 10 to 150 repeating units.

18. The copolymer of claim 16 or 17, wherein the copolymer further comprises, where chemically permissible, terminal substituents independently selected from the group consisting of:

19. A copolymer compri sing :

or an isotopic variant thereof; and

20. A composition comprising the polymer of any one of claims 1 to 12, or the copolymer of any one of claims 13 to 19, and an acceptable carrier.

21. The composition of claim 20, wherein the composition is formulated for topical administration.

22. The composition of claim 20 or 21, wherein the composition is in the form of a topical lotion, an oil, a spray, a lip balm, or a make-up cream.

23. A method of protecting a keratinous substrate from ultraviolet radiation comprising applying the polymer of any one of claims 1 to 12, the copolymer of any one of claims 13 to 19, or the composition of any one of claims 20 to 22 to a keratinous substrate of a subject in need thereof.

24. The method of claim 23, wherein the keratinous substrate is skin, hair, scalp, or nails.

25. A method of protecting skin from ultraviol ent radiation comprising applying the polymer of any one of claims 1 to 12, the copolymer of any one of claims 13 to 19, or the composition of any one of claims 20 to 22 to skin of a subject in need thereof.