Compositions and methods for targeted delivery of polylactic acid for hair growth

Abstract

A composition for treating hair loss and stimulating hair growth, the composition comprising polylactic acid (PLA) particles or derivatives thereof, in a pharmaceutically acceptable carrier; wherein the composition further comprises bacteriostatic or deionized water and at least one excipient; wherein the PLA particles or derivatives thereof are suspended in the carrier. Further disclosed is a composition comprising poly-L-lactic acid (PLLA) particles for use in a method of stimulating hair growth on a scalp of a subject, wherein the PLLA particles are suspended in a pharmaceutically acceptable carrier, wherein the composition comprises bacteriostatic or deionized water and at least one excipient, wherein the PLLA particles function as a pro-drug that degrades in situ to provide a sustained release of lactic acid to follicular cells.

Description

Attorney Docket No. DRIP101WOCOMPOSITIONS AND METHODS FOR TARGETED DELIVERY OF POLYLACTIC ACID FOR HAIR GROWTHCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Application No.63 / 720,741, filed November 14, 2024, which application is incorporated herein by reference in its entirety.FIELD

[0002] The present disclosure relates to compositions and methods utilizing polylactic acid (PLA), including poly-L-lactic acid (PLLA) to treat hair loss and stimulate hair growth. The disclosure encompasses specific formulations of PLLA as microparticles or nanoparticles, systems specifically configured for the delivery of said compositions, and methods fortheir administration to targeted regions of the scalp to promote follicular regeneration. The present disclosure further relates to modulation of mitochondrial activity and cellular energy metabolism in hair follicle cells.BACKGROUND

[0003] Poly-L-lactic acid (PLLA) is a biocompatible and bioresorbable polymer. Its primary application in dermatology has been for aesthetic soft-tissue augmentation and dermal volumization. For example, U.S. Patent Nos. 7,731,758 and 11,235,087, describe injectable PLLA compositions engineered to correct wrinkles, scars, and other contour defects by providing long-lasting structural support and bulk. The formulations in these references are optimized for volume, teaching the use of larger PLLA particles (e.g., >20 pm) and higher molecular weights (e.g., >70 kDa) to ensure longevity as a dermal filler. This focus on creating durable volume for aesthetic correction teaches away from the use of PLLA for stimulating specific cellular pathways related to hair follicle biology.

[0004] Furthermore, where PLLA is mentioned in the context of therapeutic delivery, known descriptions consistently characterize it as an inert structural carrier or excipient, rather than as a primary therapeutic agent. For instance, US Patent Publication No. 2025 / 0276034 (Kim) and International Patent Publication No. WO2022 / 035849 (Nedella) describe using PLA / PLGA polymers to form a delivery matrix for the controlled release of other active agents, such as cyclosporine derivatives or FGF-1, respectively. Similarly, Korean Reference KR 102693525 (Yoon) discloses PLLA as one of several optional emulsifying polymers for stabilizing lipid nanoparticles that encapsulate exosomes, where the exosomes are identified as the active ingredient. These references fail to recognize or suggest any intrinsic therapeutic activity of PLLA itself for hair growth.Attorney Docket No. DRIP101WO

[0005] While some known references mention PLLA in the context of hair-related procedures, they fail to provide the specific, critical details required for an effective and repeatable treatment. For example, Georgian Patent No. GE U 2021 2082 Y discloses the general concept of using PLLA, including as nanoparticles, to stimulate hair follicle stem cells. However, this reference provides no enabling disclosure regarding the specific particle sizes, molecular weights, or concentration ranges necessary to achieve a reliable therapeutic effect and furthermore is directed to threads of PLLA. Likewise, U.S. Patent No. 10,980,865 (Chang) and International Application Pub. No. WO2022 / 066845 (Tabor) mention PLLA and microneedling among a list of various general aesthetic modalities but do not teach the specific combination of a uniquely formulated PLLA composition administered to a targeted depth to achieve synergistic activation of hair follicle stem cells.

[0006] However, the use of PLLA, if not administered properly and / or at a specific dosage, can cause alopecia. (Alopecia secondary to poly-L-lactic acid dermal fillers. Nguyen, Kim T. et al.. JAAD Case Reports, Volume 58, 49 - 51).

[0007] Thus, known disclosures, taken as a whole, consistently fail to appreciate or teach the use of PLLA as a primary therapeutic agent for hair growth. The existing disclosures are limited to using PLLA for unrelated purposes such as dermal filling, as an inert delivery vehicle for other drugs. There remains a significant and unmet need for a PLLA-based composition and method that is specifically formulated, dosed, and administered for the purpose of effectively and reliably stimulating hair growth and treating alopecia.

[0008] The present disclosure addresses the growing demand for hair loss treatments by administering PLA or derivative particles to affected areas as a stand-alone agent or in combination with adjunctive regenerative treatments to modulate the follicular microenvironment and stimulate hair regrowth through both mechanical and paracrine mechanisms.SUMMARY

[0009] The present disclosure addresses the growing demand for hair loss treatments by administering PLA or derivative particles to affected areas as a stand-alone agent or in combination with adjunctive regenerative treatments to modulate the follicular microenvironment and stimulate hair regrowth through both mechanical and paracrine mechanisms.

[0010] In one aspect, the disclosure may broadly comprise a composition for treating hair loss and stimulating hair growth, the composition comprising polylactic acid (PLA) particles or derivatives thereof, in a pharmaceutically acceptable carrier; where the composition further comprises bacteriostatic or deionized water (bacteriostatic water contains .9% benzyl alcohol) and at least one excipient, where the PLA particles or derivatives thereof are suspended in the carrier.Attorney Docket No. DRIP101WOThe objective to provide compositions and methods for promoting hair growth and treating hair loss.

[0011] A unique and distinctive feature of this aspect is the use of a specifically formulated poly-L-lactic acid (PLLA) composition as the primary therapeutic agent. Disclosed is a formulation of PLLA that when administered at appropriate concentrations and delivery depths, initiates a localized regenerative response that unexpectedly increases follicular activity and restores hair density.

[0012] In another aspect, the disclosure may broadly comprise a composition for treating hair loss and stimulating hair growth, the composition comprising polylactic acid PLA particles or derivatives thereof, in a pharmaceutically acceptable carrier; where the composition further comprises bacteriostatic or deionized or sterile water and at least one excipient; where the PLA particles or derivatives thereof are suspended in the carrier.

[0013] In another exemplary aspect of the disclosure, provided is a system for treating hair loss or stimulating hair growth on a scalp of a subject, the system comprising: (a) a therapeutic composition comprising PLLA particles, in a pharmaceutically acceptable carrier, and the therapeutic composition comprising bacteriostatic or deionized water and at least one excipient; wherein the PLLA particles are suspended in the carrier, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling; and, (b) a set of instructions directing that the composition be administered to the scalp and that microneedling be performed on the scalp in a manner that provides enhancement of hair growth.

[0014] In another aspect, a method for promoting hair growth or treating hair loss in a subject in need thereof is provided, the method comprising, administering to the subject a therapeutic composition comprising PLLA particles, in a pharmaceutically acceptable carrier; and, the therapeutic composition comprising bacteriostatic or deionized water and at least one excipient, wherein the PLLA particles are suspended in the carrier, wherein the PLLA particles function as a pro-drug by degrading in situ to provide a sustained release of lactic acid, thereby modulating mitochondrial metabolism in hair follicle mesenchymal stem cells and dermal white fat tissues to stimulate hair follicle growth in follicular cells to stimulate hair growth, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

[0015] In one aspect, the disclosure provides a device for treating hair loss or stimulating hair growth on a scalp, the device comprising: (a) a therapeutic composition comprising PLLA particles suspended in a pharmaceutically acceptable carrier, wherein the therapeutic composition comprisesAttorney Docket No. DRIP101WObacteriostatic or deionized water and at least one excipient; (b) an apparatus for administering the therapeutic composition; and, (c) a set of instructions for use, the instructions directing an operator to use the apparatus to administer the composition and / or an adjunct topical ingredient to the scalp; wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

[0016] In one aspect, a composition for stimulating hair growth is provided, the composition comprising: (a) PLLA particles, in a pharmaceutically acceptable carrier; (b) one or more excipients; and, (c) bacteriostatic or deionized water; wherein the PLLA particles are suspended in the carrier, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling, wherein the particles are formulated as a sustained-release depot for lactic acid.

[0017] In one aspect, the disclosure provides a composition comprising PLLA particles for use in a method of stimulating hair growth on a scalp of a subject, wherein the PLLA particles are suspended in a pharmaceutically acceptable carrier, wherein the composition comprises bacteriostatic or deionized water and at least one excipient, wherein the PLLA particles function as a pro-drug that degrades in situ to provide a sustained release of lactic acid to follicular cells.

[0018] In one aspect, the disclosure provides a system for treating hair loss or stimulating hair growth on a scalp of a subject, the system comprising: (a) a therapeutic composition comprising PLLA particles, in a pharmaceutically acceptable carrier, and comprising bacteriostatic or deionized water and at least one excipient; wherein the PLLA particles are suspended in the carrier, wherein the therapeutic composition is formulated to function as a pro-drug for lactic acid wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling; and, (b) a set of instructions directing that the composition be administered to the scalp and that microneedling be performed on the scalp in a manner that provides enhancement of hair growth.

[0019] In one aspect, the disclosure provides a composition for stimulating hair growth, the composition comprising: (a) PLLA particles, in a pharmaceutically acceptable carrier; (b) one or more excipients; and, (c) bacteriostatic or deionized water; wherein the PLLA particles are suspended in the carrier, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling, wherein the particles are formulated as a sustained-release depot for lactic acid.

[0020] PLLA can be administered to promote hair growth on the scalp, particularly for treating pattern baldness through subdermal injection into the frontal and temporal regions. This effect is observed in both male and female patients. Even more unexpectedly, the therapeutic benefit isAttorney Docket No. DRIP101WOhighly dependent on precise injection of the PLLA formulation; improper placement or technique may diminish efficacy or, in some cases, contribute to additional hair loss.

[0021] The disclosure provides compositions and methods that address these challenges and reliably elicit the desired hair-promoting effect. Histologic and clinical studies of poly-L-lactic acid have demonstrated dermal fibroblast activation, collagen deposition, and gradual neocollagenesis. These processes contribute to improved dermal support and follicular environment stability without reliance on volumetric filling effects. Clinical observations demonstrate increased follicular density within several weeks, consistent with neocollagenesis; induced fibroblast activation and type I / III collagen synthesis and improved dermal matrix structure. Treatment enhances dermal structure and supports follicular anchoring through collagen remodeling.

[0022] The use of poly-L-lactic acid (PLLA) as a biostimulatory agent is based on its ability to induce a controlled inflammatory response and subsequent tissue remodeling. Following injection, PLLA particles are encapsulated by fibroblasts and immune cells, triggering the upregulation of key signaling molecules such as transforming growth factor-P (TGF-P) and collagen type I (COL1A1) (Brady et al., 1973; Oh et al., 2023). While this process has been traditionally utilized for gradual volumization in aesthetic applications, aspects of the disclosure are based on the discovery of its novel application in hair follicle regeneration, improving angiogenesis, fibroblast senescence, ECM remodelings, and scalp health.

[0023] Preclinical studies suggest that PLLA administration influences the gene expression of molecules critical to hair biology, including hepatocyte growth factor (HGF) (Waibel et al., 2024). HGF is a pivotal signaling molecule that extends the anagen (growth) phase of the hair cycle, promotes keratinocyte proliferation, and activates the Wnt / p-catenin pathway via its c-Met receptor (Xu et al., 2016; Shimaoka et al., 2001). The anatomical depth targeted by the methods of the present disclosure, is where the dermal papilla and dermal white adipose tissue (dWAT) reside. These structures are essential for hair cycling and are known to secrete HGF, suggesting that PLLA's biostimulatory effect directly enhances the natural regenerative signaling within the follicular niche (Nicu et al., 2021; Zhang et al., 2021). Accordingly, various aspects and embodiments of the disclosure leverage the aforementioned.

[0024] In one aspect, the therapeutic effect of PLLA is further potentiated by combining its administration with adjunctive regenerative techniques, such as microneedling. Microneedling has been shown to induce a controlled micro-injury that triggers a wound-healing cascade and the release of endogenous growth factors, including platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF) (English Jr. et al., 2022). This controlled inflammatory response enhances perifollicular vascularity and creates an optimized microenvironment for theAttorney Docket No. DRIP101WObiostimulatory action of PLLA.

[0025] The method may be further enhanced by performing the microneedling procedure with a glide medium containing additional bioactive agents. In one aspect, the glide medium comprises PDGF, which is a potent mitogen for dermal fibroblasts and endothelial cells that promotes the neovascularization and tissue remodeling critical for sustaining anagen-phase follicles (Mehta et al., 2025). In another aspect, the glide medium comprises polynucleotides (PN). PNs have been shown to enhance fibroblast proliferation, protect against oxidative stress, and stimulate collagen synthesis through adenosine A2 receptor signaling, mechanisms which may synergize with the delayed biostimulatory effects of PLLA (Lee et al., 2024; Abuyousif et al., 2025).

[0026] The foregoing, and later recited aspects or aspects, are important as hair loss is a common and progressive condition affecting both men and women. Among women, female pattern hair loss (FPHL) is the most prevalent form and is characterized by follicular miniaturization, reduced hair density, and disrupted anagen-to-telogen ratios. Normal scalp hair exhibits an anagen-to-telogen ratio of approximately 12:1 to 14:1, while androgenic alopecia can reduce this ratio to as low as 5:5. FPHL affects over 55% of women during their lifetime, with prevalence increasing from approximately 12% in women aged 20-29 years to more than 50% of women over age 80. Hair loss has substantial psychosocial consequences, including emotional distress, diminished self-esteem, and decreased quality of life. The described aspects and aspects of the present disclosure at least mitigate these consequences.

[0027] In addition to FPHL, many individuals’ experience alopecia areata and other alopecia subtypes, which can result in patchy, diffuse, or total hair loss. Alopecia areata is believed to arise from genetic, hormonal, or autoimmune factors, and may be triggered by psychological stress or illness. In severe cases, patients may develop alopecia totalis or alopecia universalis. All hair loss conditions ultimately reflect disruptions in the hair cycle, which consists of anagen (growth), catagen (regression), and telogen (resting) phases. Some descriptions of the hair growth cycle include the exogen phase to describe hair shedding. Under normal conditions, approximately 88% of scalp hairs are in anagen and only about 1% in catagen. With progressive alopecia, an increasing proportion of follicles transition to telogen or miniaturize from terminal to vellus morphology, producing clinically visible thinning. Approximately 50% hair loss is required before thinning becomes apparent. Aging and androgenic hair loss are increasingly linked to mitochondrial dysfunction, altered NAD / NADH balance, and impaired pyruvate metabolism, contributing to follicular miniaturization and stem cell exhaustion.

[0028] Despite the high prevalence of hair loss, current therapeutic options remain limited. Treatments such as topical minoxidil, oral finasteride or dutasteride, platelet-rich plasma (PRP),Attorney Docket No. DRIP101WOlow-level laser therapy, and anti androgenic agents often provide inconsistent, partial, or temporary benefit and generally require ongoing use to maintain results. Attempts to modify hormonal pathways, including the systemic or topical administration of androgen-modulating agents, have produced variable and often disappointing outcomes. More invasive approaches such as hair transplantation can yield cosmetic improvement but are costly, painful, and capable of replacing only a fraction of the hair density present on a healthy scalp. As a result, there remains a significant unmet need for safe, effective, and durable treatments for hair loss, which is addressed by the described aspects and aspects of the present disclosure.

[0029] Any feature or combination of features described herein are included within the scope of the present disclosure, or aspects thereof, provided that the features included in any such combination are not mutually inconsistent as will be apparent from the context, this specification, and the knowledge of one of ordinary skill in the art. Additional advantages and aspects of the present disclosure are apparent in the following detailed description and claims.

[0030] An advantage of the various embodiments or aspects of the present disclosure is the provision of a safe, effective, and durable treatment for hair loss that addresses the shortcomings of the prior art. The specifically formulated PLA or derivative polymer composition provides an unexpected biological advantage at the cellular level of the hair follicle, leading to a potent and efficient stimulation of the hair cycle, a mechanism fundamentally different from the volumizing foreign body response of known dermal fillers. A system distributing PLA or derivative polymer overcomes significant technical problems including uniformly delivering a particle suspension.

[0031] A key advantage is that PLLA, when administered at appropriate concentrations and delivered to the correct depth, advantageously initiates a localized regenerative response that increases follicular activity and restores hair density. This method provides a more durable and comprehensive improvement in hair health compared to current treatments by addressing the underlying structural integrity of the scalp itself, rather than relying solely on hormonal modulation or temporary vasodilation. The biostimulatory effect of PLLA induces long-lasting neocollagenesis, rebuilding the dermal matrix and increasing collagen density around the hair follicles, uniformly delivering a particle suspension with potential sustained delayed release. This restored dermal framework provides enhanced structural and metabolic support to the follicle, creating a healthier and more robust foundation from which the hair can grow. None of the presently known references or works teach the use of PLLA to achieve this unique therapeutic outcome.

[0032] These and other objects, features, and advantages of the present disclosure will become readily apparent upon a review of the following detailed description of the present disclosure, inAttorney Docket No. DRIP101WOview of the drawings and appended claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Various embodiments or aspects are disclosed, by way of example only, with reference to the accompanying schematic drawings in which corresponding reference symbols indicate corresponding parts, in which:Figure la and lb are diagrams illustrating the chemical structures of L-lactic acid and D-lactic acid monomers;Figure 2a is a cross-section view of human skin layers;Figure 2b is an anatomic illustration;Figure 3 is a chart defining hair type categories;Figure 4a and 4b provide results showing a comparison of a scalp treatment area before administration and after administration of a composition in accordance with an aspect of the present disclosure;Figure 5s and 5b provide results showing a comparison of a scalp treatment area before administration and after administration of a composition in accordance with an aspect of the present disclosure;Figure 6a and 6b provide results showing a comparison of a scalp treatment area before administration and after administration of a composition in accordance with an aspect of the present disclosure;Figure 7a and 7b provide results showing a comparison of a scalp treatment area before administration and after administration of a composition in accordance with an aspect of the present disclosure; and,Figure 8a and 8b provide results showing a comparison of a scalp treatment area before administration and after administration of a composition in accordance with an aspect of the present disclosure.Figures 9a-9e provide before and after photos of human patients administered PLLA according to aspects of the present disclosure; and,Figures 10a and 10b a PLA or derivative composition delivery device.DETAILED DESCRIPTION

[0034] At the outset, it is to be understood that the claims are not limited to the disclosed aspects. Furthermore, it is understood that this disclosure is not limited to the particular methodology, materials and modifications described and as such may, of course, vary. It is also understood that the terminology used herein is for the purpose of describing aspects only and is not intended to limit the scope of the claims.Attorney Docket No. DRIP101WO

[0035] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one having skill in the art to which this disclosure pertains. Thus, certain terms that are used to describe the disclosure are discussed below, or elsewhere in the specification, to provide additional guidance to the practitioner regarding the description of the disclosure. It will be appreciated that the same thing can be said in more than one way. In this same breadth, any methods, devices, materials, elements, compounds, similar or equivalent to those described herein can be used in the practice or testing of the example embodiments or aspects.

[0036] Consequently, alternative language and synonyms may be used for any one or more of the terms discussed herein. Nor is any special significance to be placed upon whether a term is elaborated or discussed herein. Synonyms for certain terms are provided. A recital of one or more synonyms does not exclude the use of other synonyms.

[0037] The word “example” or “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any implementation described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other implementations. Likewise, the disclosure is not limited to the various embodiments or aspects given in this specification.

[0038] Therefore, reference in this specification to "one embodiment / aspect" or "an embodiment / aspect" means that a particular feature, structure, or characteristic described in connection with the embodiment / aspect is included in at least one embodiment / aspect of the disclosure. The use of the phrase "in one embodiment / aspect" or "in another embodiment / aspect" in various places in the specification does not necessarily all refer to the same embodiment / aspect, nor are separate or alternative embodiments / aspects mutually exclusive of other embodiments / aspects. Moreover, various features are described that may be exhibited by some embodiments / aspects and not by others. Similarly, various requirements are described, which may be requirements for some embodiments / aspects but not others embodiments / aspects. Embodiment and aspect can, in certain instances, be used interchangeably.

[0039] If the specification states a component, element, or feature “may,” “can,” “could,” “should,” “would,” “preferably,” “possibly,” “typically,” “optionally,” “for example,” “often,” or “might” (or other such language) be included or have a characteristic, that a specific component or feature is not required to be included or to have the characteristic. Such a component, element, or feature may be optionally included in some embodiments, or it may be excluded.

[0040] It should be noted that the terms “including”, “includes”, “having”, “has”, “contains”, and / or “containing”, should be interpreted as being substantially synonymous with the terms “comprising” and / or “comprises”.Attorney Docket No. DRIP101WO

[0041] It should be appreciated that the term “substantially” is synonymous with terms such as “nearly,” “very nearly,” “about,” “approximately,” “around,” “bordering on,” “close to,” “essentially,” “in the neighborhood of,” “in the vicinity of,” etc., and such terms may be used interchangeably as appearing in the specification and claims. It should be appreciated that the term “proximate” is synonymous with terms such as “nearby,” “close,” “adjacent,” “neighboring,” “immediate,” “adjoining,” etc., and such terms may be used interchangeably as appearing in the specification and claims. The term “approximately” is intended to mean values within ten percent of the specified value.

[0042] It should be understood that use of “or” in the present application is with respect to a “nonexclusive” arrangement, unless stated otherwise. For example, when saying that “item x is A or B,” it is understood that this can mean one of the following: (1) item x is only one or the other of A and B; (2) item x is both A and B. Alternately stated, the word “or” is not used to define an “exclusive or” arrangement. For example, an “exclusive or” arrangement for the statement “item x is A or B” would require that x can be only one of A and B. Furthermore, as used herein, “and / or” is intended to mean a grammatical conjunction used to indicate that one or more of the elements or conditions recited may be included or occur. For example, a compound comprising a first element, a second element and / or a third element, is intended to be construed as any one of the following structural arrangements: a compound comprising a first element; a compound comprising a second element; a compound comprising a third element; a compound comprising a first element and a second element; a compound comprising a first element and a third element; a compound comprising a first element, a second element and a third element; or, a compound comprising a second element and a third element.

[0043] Moreover, as used herein, the phrases “comprises at least one of’ and “comprising at least one of’ in combination with an element is intended to mean that the element includes one or more of the elements listed after the phrase. For example, a compound comprising at least one of: a first element; a second element; and, a third element, is intended to be construed as any one of the following arrangements: a compound comprising a first element; a compound comprising a second element; a compound comprising a third element; a compound comprising a first element and a second element; a compound comprising a first element and a third element; a compound comprising a first element, a second element and a third element; or, a compound comprising a second element and a third element. A similar interpretation is intended when the phrase “used in at least one of:” is used herein.

[0044] Without intent to further limit the scope of the disclosure, examples of instruments, apparatus, methods, and their related results according to the embodiments of the present disclosureAttorney Docket No. DRIP101WOare given below. Note that titles or subtitles may be used in the examples for the convenience of a reader, which in no way should limit the scope of the disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. In the case of conflict, the present document, including definitions, will control.

[0045] As used herein, the terms “subject” and “patient” are used interchangeably. As used herein, a subject can be a mammal such as a non-primate (e.g., cows, pigs, horses, cats, dogs, rats, etc.) or a primate (e.g., monkey and human). In specific embodiments, the subject is a human. As the patients and subjects of the disclosure method are, in addition to humans, veterinary subjects, formulations suitable for these subjects are also appropriate.

[0046] The term “supplements”, as used herein, refers to products intended for oral ingestion that contain one or more dietary ingredients to supplement the diet and support overall health, including the health of hair, skin, and nails. These ingredients may include, but are not limited to, vitamins, minerals, herbs or other botanicals, amino acids, and other substances such as enzymes, organ tissues, glandulars, and metabolites. Supplements can be provided in various forms, such as tablets, capsules, softgels, gelcaps, liquids, or powders. In the context of the present invention, supplements are agents that provide essential nutrients and bioactive compounds that support the cellular processes involved in hair follicle cycling and hair shaft production, thereby complementing the localized biostimulatory effects of the PLLA composition.

[0047] The term “subdermal” refers to the area below the skin, including the subcutaneous region. Similarly, the term “intradermal” refers to regions within the dermis, which lies beneath the epidermis and may be further divided into the superficial dermis, mid dermis, and deep dermis. The superficial dermis is located immediately below the epidermis, the mid dermis is the intermediate layer, and the deep dermis is the layer adjacent to the dermal-fat junction, which is the interface between the deep dermis and the underlying subcutaneous fat. For example, an intradermal injection delivers fluid into one or more of these dermal layers. The term “hypodermal” refers to or of the hypodermis, which is the innermost layer of skin. It can also mean lying beneath the epidermis, the outer layer of the skin.

[0048] The term “medicament,” “active agent,” or “active ingredient” refers to a substance, compound, or molecule that is biologically active or otherwise, induces a biological or physiological effect on a subject to which it is administered. In other words, “active agent” or “active ingredient” refers to a component or components of a composition to which the whole or part of the effect of the composition is attributed. An active agent can be a primary active agent, or, in other words, the component(s) of a composition to which the whole or part of the effect ofAttorney Docket No. DRIP101WOthe composition is attributed. An active agent can be a secondary agent, or in other words, the component(s) of a composition to which an additional part and / or other effect of the composition is attributed.

[0049] It should be understood that a “pharmaceutical composition” is intended to include the combination of an active agent with a carrier, inert or active, in a sterile composition suitable for diagnostic or therapeutic use in vitro, in vivo, or ex vivo. In one aspect, the pharmaceutical composition is substantially free of endotoxins or is non-toxic to recipients at the dosage or concentration employed. The pharmaceutical composition may be a coating, a powder, a compound, a time-release agent, a paste, a pill, a tablet, a chewable, a dragee, a pellet, a granulate, a liquid, an aerosol, an injectable, a suppository, a dissolvable tablet, or any other known formulation for delivery. The pharmaceutical composition may be contained within a vial, a blister pack, a capsule, a cartridge, a carpule, a reservoir, a container, or within any form of transdermal tape, applicator, needled apparatus or needle-free delivery devices. Other known formulations and methods of delivery that are known in the art are inherently contemplated by the disclosure of the present disclosure.

[0050] As used herein, the terms “treating,” “treatment,” and the like are used to mean obtaining a desired pharmacologic and / or physiologic effect. The effect may be prophylactic in terms of completely or partially preventing a disorder or sign or symptom or spread of infection thereof, and / or may be therapeutic in terms of amelioration of the symptoms of the disease or spread of infection, or a partial or complete cure for a disorder and / or adverse effect attributable to the disorder or infection.

[0051] The term “bioavailability” refers to the fraction of an administered dose of unchanged drug that reaches the systemic circulation. For example, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes (such as orally), its bioavailability generally decreases due to incomplete absorption and first-pass metabolism. Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration.

[0052] The term “compound” or “formulation” refers to a combined mixture of multiple ingredients. A compound or formulation may further refer to a customized formulation of ingredients designed for therapeutic, prophylactic, preventative, and aseptic purposes.

[0053] The term “an effective amount” refers to the amount of the defined component sufficient to achieve the desired chemical composition or the desired therapeutic result. The desired result is the alleviation or amelioration of the signs, symptoms, or causes of a skin disease, or any otherAttorney Docket No. DRIP101WOdesired alteration of a biological system, including promoting hair growth. When the desired result is a therapeutic response, the effective amount will, without limitation, vary depending upon the specific disease or symptom to be treated or alleviated, the age, gender, sex and weight of the subject to be treated, the dosing regimen of the formulation, the severity of the disease condition, the manner of administration and the like, all of which can be determined readily by one of skill in the art. A desired effect may, without necessarily being therapeutic, also be a cosmetic effect, for hair growth as described herein.

[0054] An "effective concentration" refers to enough of an agent to produce an intended effect. The amount will vary for each compound and upon known factors such as pharmaceutical characteristics, the type of medical device, age, sex, health, and weight of the recipient, and the use and length of use. It is within the skilled artisan's ability to relatively easily determine an effective concentration for each compound.

[0055] The term “cosmeceutical” refers to a substance that includes a cosmetic with one or more "biologically active ingredients." Products which are similar in perceived benefits but ingested orally are known as nutricosmetics.

[0056] The term “chemical permeation enhancer” or “CPE” refers to a molecule that interacts with the constituents of skin's outermost layer, the stratum comeum (SC), and increases its permeability.

[0057] The term “dermal filler” (also referred to as injectable implants, soft tissue fillers, lip and facial fillers, or wrinkle fillers) a medical device implant for use in helping to create a smoother and / or fuller appearance in the face, including nasolabial folds. Dermal fillers can help diminish facial lines and restore volume and fullness in the face. Common dermal fillers include Hyaluronic acid (Restylane®), calcium hydroxylapatite (Radiesse®), poly-L-Iactic acid (Sculptra®) and polymethylmethacrylate (PMMA) (Bellafill®).

[0058] The term “microneedling” refers to a minimally invasive procedure for skin. A healthcare provider uses thin needles to make tiny holes in the top layer of the skin. The damage helps stimulate your skin's healing process, so it produces more collagen and elastin. It can be used to treat a variety of skin conditions that cause depressions in the skin such as acne scarring, surgical scars, other scars, burns, enlarged pores, wrinkles and stretch marks.

[0059] The term “microneedle fractional radiofrequency” or “MFRF” refers to a minimally invasive cosmetic procedure that uses tiny needles to deliver radiofrequency (RF) energy directly into the deeper layers of the skin, stimulating collagen production and remodeling to improve skin texture, reduce wrinkles, acne scars, and address other signs of aging, all while causing minimal downtime; essentially, it combines the micro- injury effect of traditional microneedling with theAttorney Docket No. DRIP101WOheating power of radiofrequency to achieve deeper skin rejuvenation.

[0060] The term "micro thread hair growth" refers to a hair restoration treatment where tiny, absorbable threads made of polydioxanone (PDO) are inserted into the scalp to stimulate hair growth by promoting blood circulation, collagen production, and activating dormant hair follicles, essentially creating a supportive environment for new hair to grow; this is considered a minimally invasive procedure that can help with thinning hair or mild hair loss.

[0061] The term “finasteride", sold under the brand names Proscar and Propecia among others, is a medication used to treat pattern hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair growth in women. It is usually taken orally, but there are formulations for patients with hair loss, designed to minimize systemic exposure by acting specifically on hair follicles. Finasteride is a 5a-reductase inhibitor and therefore an antiandrogen. It works by decreasing the production of dihydrotestosterone (DHT) by about 70%. In addition to DHT, finasteride also inhibits the production of several anticonvulsant neurosteroids including allopregnanolone, androstanediol, and tetrahydrodeoxycorticosterone.

[0062] The term “minoxidil” refers to a medication used for the treatment of high blood pressure and pattern hair loss. It is an antihypertensive and a vasodilator. It is available as a generic medication by prescription in oral tablet form and over the counter as a topical liquid or foam. The mechanism by which minoxidil promotes hair growth is not fully understood. Minoxidil is an adenosine 5'-triphosphate-sensitive potassium channel opener, causing hyperpolarization of cell membranes. Theoretically, by widening blood vessels and opening potassium channels, it allows more oxygen, blood, and nutrients to the follicles. Moreover, minoxidil contains a nitric oxide moiety and may act as a nitric oxide agonist. This may cause follicles in the telogen phase to shed, which are then replaced by thicker hairs in a new anagen phase.

[0063] The term “Aldactone®” or “spironolactone” refers to a diuretic that can be used to treat high blood pressure and heart failure. It can also reduce swelling related to heart, kidney or liver disease.

[0064] The term “Sculptra®” refers to a proprietary formulation of poly-L-lactic acid (PLLA) that is an FDA-approved dermal filler. PLLA was approved by the FDA for the treatment of facial fat loss (also called facial lipoatrophy).

[0065] All numerical designations, e.g., pH, temperature, time, concentration, and molecular weight, including ranges, are to be understood as approximations in accordance with common practice in the art. When used herein, the term “about” may connote variation (+) or (-) 1%, 5% or 10% of the stated amount, as appropriate given the context. It is to be understood, although not always explicitly stated, that the reagents described herein are merely exemplary and thatAttorney Docket No. DRIP101WOequivalents of such are known in the art.

[0066] Many known and useful compounds and the like can be found in Remington's Pharmaceutical Sciences (13th Ed), Mack Publishing Company, Easton, PA, a standard reference for various types of administration. As used herein, the term “formulation(s)” means a combination of at least one active ingredient with one or more other ingredients, also commonly referred to as excipients, which may be independently active or inactive. The term “formulation” may or may not refer to a pharmaceutically acceptable composition for administration to humans or animals and may include compositions that are useful intermediates for storage or research purposes.

[0067] In some aspects, the present disclosure features compositions for treating hair loss or stimulating hair growth. In some aspects, the composition comprises polylactic acid (PLA) or a derivative thereof and a pharmaceutically acceptable carrier. In other aspects, the composition comprises poly-L-lactic acid (PLLA) and a pharmaceutically acceptable carrier. In further aspects, the composition comprises poly-D-lactic acid (PDLA) and a pharmaceutically acceptable carrier. In some aspects, the composition may further comprise one or more excipients, such as carriers, stabilizers, or bulking agents (e.g., carboxymethylcellulose, mannitol).

[0068] An important feature of the various aspects is the use of a specifically formulated PLLA polymer composition as a primary therapeutic agent for stimulating hair growth. This polymer composition is defined by critical parameters, including a PLLA polymer average molecular weight, particle size, and concentration range. Another key feature is a method of use wherein this specific PLLA polymer composition is administered to a targeted subdermal depth (See Figure 3), to reach the hair follicle bulge region, and is optionally performed in synergistic combination with microneedling to enhance hair follicle stem cell activation. A further feature includes incorporation into a device comprising a microneedle array and a reservoir specifically engineered to uniformly dispense the PLLA particle suspension without clogging or settling.

[0069] In some aspects, derivatives of PLA may include but are not limited to PLLA, PDLA, and poly-D, L-lactic acid (PDLLA). Figure 1 shows the chemical structure of either enantiomer of lactic acid, on the left the S, (+), L lactic acid, or on the right the R, (-), or D lactic acid. Figure 2 depicts the general structure of L polylactic acid to PLLA.

[0070] Aspects include dermatologic compositions and methods utilizing polylactic PLA, including PLLA to treat hair loss and stimulate hair growth, particularly in cases where conventional methods of promoting hair growth are ineffective.

[0071] In some aspects, the PLA or a derivative particle used in the composition may have a weight-average molecular weight (MW) selected from different commercially available grades or may be a blend of two or more PLA or derivative polymers having different molecular weights toAttorney Docket No. DRIP101WOachieve desired viscosity, injectability, and degradation characteristics.

[0072] PLA or derivative particles hydrolyze in aqueous solution, leading to the release of lactic acid monomers and lower MW polymers from bulk polymer particles as well as to fragmentations of bulk polymer particles, where the process is self-catalyzed by the presence of degradation products.

[0073] PLA or a derivative particle may function as a localized, sustained-release depot for lactic acid. Recent findings, such as those described in International Application No. PCT / US2023 / 086052 suggest that enhancing local lactate production can promote hair growth, potentially by inhibiting mitochondrial pyruvate oxidation (MPO) and the mitochondrial pyruvate carrier (MPC) in follicular cells. By delivering a steady and prolonged supply of lactic acid directly to the hair follicle microenvironment in situ, the present disclosure modulates cellular metabolism to stimulate hair growth. This supports a novel mechanism of action, using PLA or a derivative as a pro-drug for lactic acid to modulate cellular metabolism in follicular cells, and represents a significant departure from the prior art's use of PLA or a derivative as a simple structural filler and explains the unexpected efficacy of the present disclosure for stimulating hair growth.

[0074] The compositions and methods of the present invention are specifically directed to the new use of PLA or a derivative for stimulating hair growth and are expressly distinguished from prior art uses of PLA or a derivative for dermal volume augmentation or wrinkle filling. The formulations described herein are intentionally prepared in a manner that makes them optimized for biostimulation of the follicular niche and, consequently, suboptimal for providing the bulk structural support required of a dermal filler.

[0075] The hydrogel and PLA, or a derivative particle ratio, can be changed. Such a formulation, combined with the natural hydrolysis of PLA or a derivative in an aqueous carrier, preferentially favors the creation or bioavailability of different molecular weight PLA or a derivative particle. These different particles have a higher surface-area-to-volume ratio, which facilitates more cellular interaction at the follicular level, but provides poor and unpredictable volume. This less-concentrated, lower-viscosity formulation, which is unsuitable for its known purpose of dermal filling, produces the unexpected and potent result of stimulating hair growth for treating hair loss and not for dermal volume augmentation or wrinkle filling.

[0076] In some aspects, the average MW of the PLA or derivative particles are about 40kDa to 50kDa. In some aspects, the average MW of the PLA or a derivative particles are about lOkDa to about lOOkDa, about lOkDa to about 90kDa, about lOkDa to about 80kDa, about lOkDa to about 70kDa, about IkDa to about 30kDa, about 50kDa to about lOOkDa, about 60kDa to about 120kDa, and about 80kDa to about 140kDa or more.Attorney Docket No. DRIP101WO

[0077] It is an aspect of the disclosure that the PLA or derivative particles have a low average molecular weight and / or small particle size, which can provide unexpected bioavailability and efficacy for stimulating hair follicle stem cells. Commercially available PLLA for dermal fillers, such as that disclosed in U.S. Patent Nos. 7,731,758 and 11,235,087, typically have a high molecular weight (e.g., 70-200 kDa, or between 70 and 500 kDa) and larger particle size (e.g., greater than 20 pm, greater than 40 pm, and between 40 and 100 pm) engineered for structural support and long-lasting volume. Original designs of this particle utilized sieving of the microparticles on a 100 pm stain-less steel sieve, shifting the distribution of species of PLA or derivative particles lower than 100 pm. High MW, large-particle PLA or derivative particles may or may not be suboptimal for stimulating the cellular pathways of the hair follicle. Specific proportions of additional chemicals (inert ingredients) are utilized to maintain larger particle sizes over smaller particle sizes, changing the equilibrium between larger particles over smaller particles. Dilution of inert ingredients such as carboxymethylcellulose and nonpyrogenic mannitol is taught against by the prior art.

[0078] PLA or derivative particles are subject to natural hydrolysis in an aqueous environment. The present disclosure contemplates this low molecular weight, small-particle-size fraction. This can be achieved, for example, by subjecting a standard PLA or a derivative particle composition to a process of controlled hydrolysis, or by using separation techniques such as size-exclusion filtration or ultracentrifugation gradients to isolate low molecular weight particles. Hydrolyzed or selected higher or lower MW fractions of PLA or a derivative particle may exhibit unexpectedly high bioavailability at the cellular level of the hair follicle bulge, distinguishing from same purposed for and relating to commercially available PLLA for dermal fillers.

[0079] In some aspects, the average MW of the PLA or a derivative is about 5 to 50 kDA. In some aspects, the average MW of the PLA or a derivative is about 5 to 30 kDA. In some aspects, the average MW of the PLA or a derivative is about 5 to 10 kDA. In some aspects, the average MW of the PLA or a derivative is about 10 to 50 kDA. In some aspects, the average MW of the PLA or a derivative is about 10 to 30 kDA. In some aspects, the average MW of the PLA or a derivative is less than 10 kDA.

[0080] In some aspects, the PLA or a derivative thereof (e.g., PLLA) is formulated as a nanoparticle or a microparticle. In certain aspects, the particles have an average size of less than 10 pm, preferably less than 5 pm, and more preferably less than 1 pm. In some aspects, the particles are nanoparticles with an average size between 50 nm and 500 nm. In certain aspects, the particles have an average size of less than 10 pm. In some aspects, the particles have an average size of about 10 pm. In some aspects, the particles have an average size of about 15 pm. In some aspects,Attorney Docket No. DRIP101WOthe particles have an average size of about 20 pm. In some aspects, the particles have an average size of about 10 to 20 pm. In some aspects, the particles have an average size of about 10 to 15 pm.

[0081] In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 15 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 14 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 13 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 12 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 11 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 10 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 10 to 15 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 12 to 15 mg / mL. In certain aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 1 to 20 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 1 to 10 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 5 to 20 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 5 to 10 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of less than 5 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 15 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 14 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 13 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 12 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration of about 11 mg / mL. In some aspects, the composition may comprise PLA or a derivative thereof at a concentration less than 10 mg / mL, preferably less than 5 mg / mL, and more preferably less than 1 mg / mL.

[0082] The compositions of the present disclosure comprise PLA or derivative particles suspended in a pharmaceutically acceptable carrier. The primary carrier component is typically a physiologically acceptable solvent that provides the bulk of the formulation's volume. Non-limiting examples of suitable solvents include sterile water, saline, buffered saline, Ringer's solution (e.g., lactated Ringer’s solution), and dextrose solutions.

[0083] To achieve the desired physical properties for injectability and stability, the compositionAttorney Docket No. DRIP101WOfurther comprises one or more excipients. These excipients can modify viscosity, enhance stability of the suspension, and act as bulking agents or cryoprotectants in lyophilized formulations.

[0084] In some aspects, a viscoelastic or hydrogel-forming carrier is included to increase viscosity and ensure a uniform suspension of the PLA or derivative particles. Suitable hydrogelforming polymers include, but are not limited to, carboxymethylcellulose (such as sodium carboxymethylcellulose), hydroxypropyl methylcellulose, hyaluronic acid, poloxamers, collagen-based hydrogels, albumin-based hydrogels, and plasma gels.

[0085] In other aspects, a bulking agent is included, which can be useful in formulations prepared by lyophilization. Non-limiting examples of such excipients include mannitol, trehalose, sorbitol, and sucrose, and appropriate analogues thereof.

[0086] Optimizing the scalp’s microenvironment plays a critical role in promoting healthy hair growth. The scalp provides a dynamic framework that supports follicular function, and its condition directly influences the anagen-telogen balance within the hair cycle. Enhancing vascular perfusion and oxygenation improves nutrient delivery to the dermal papilla, while reducing inflammation, oxidative stress, and microbial dysbiosis helps preserve the integrity of the perifollicular environment. Restoration of the scalp barrier and maintenance of adequate hydration further support epithelial cell turnover and signaling pathways essential for follicular regeneration. Collectively, these factors improve the overall quality of the scalp tissue and create physiologically favorable conditions that promote robust, sustained hair growth.

[0087] In certain aspects, the compositions described herein may be enhanced by the inclusion of one or more optional additives that provide a complementary therapeutic effect. These additives can be co-formulated with the PLA or derivative particles or administered in conjunction with the primary treatment. In one aspect, the composition further comprises a conventional hair-loss therapeutic. Non-limiting examples of such therapeutics include 5 -alpha-reductase inhibitors such as minoxidil, finasteride, and dutasteride. The inclusion of these agents can provide a multi-modal approach to treating alopecia by combining the biostimulatory effect of PLA or derivative particles with established hormonal or vasodilatory pathways.

[0088] The compositions of the present disclosure comprise the active poly-lactic acid (PLA) particles suspended in a pharmaceutically acceptable carrier system. This system is formulated with specific excipients to ensure the stability, injectability, and efficacy of the final product. The primary component of the carrier is a physiologically acceptable aqueous solvent, such as bacteriostatic or deionized water, sterile water for injection, saline, buffered saline, or a balanced electrolyte solution like Lactated Ringer’s solution. To ensure the PLA particles or derivatives thereof remain uniformly suspended, the composition includes a gelling agent to form a hydrogel.Attorney Docket No. DRIP101WOSuitable hydrogel-forming polymers include cellulose derivatives such as Carboxymethylcellulose (CMC) and hydroxypropyl methylcellulose (HPMC), as well as more complex hydrogels like collagen-based hydrogels, albumin-based hydrogels, and plasma gels. The composition may further comprise a bulking agent, which is particularly useful in lyophilized formulations to provide structure and to act as a cryoprotectant. Non-limiting examples of such agents include sugar alcohols such as mannitol, trehalose, and sorbitol. Glycerol may also be included as a humectant and tonicity agent.

[0089] In other aspects, the PLLA composition may be administered in conjunction with, or coformulated with, one or more additional hair growth-promoting products or bioactive agents to potentiate the regenerative environment of the scalp. These agents can work synergistically with the PL A particles or derivatives thereof to support follicular health. For example, the composition may include established pharmaceutical agents for treating alopecia, such as potassium channel openers like Minoxidil (which may be formulated for topical, oral, or injectable use) and 5 alphareductase inhibitors like Finasteride (oral or topical) and dutasteride.

[0090] The composition may also include advanced biologies to enhance the regenerative effect. This class of agents includes purified growth factors, such as Fibroblast Growth Factor (FGF), Platelet-Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), and Insulin-like Growth Factor (IGF-1). It also encompasses therapies based on autologous preparations like Platelet-Rich Plasma (PRP), which is a source of these endogenous growth factors. In other aspects, the composition may include Exosomes, which are nanovesicles that facilitate intercellular communication and deliver regenerative signals. Further examples of advanced agents include those targeting various cellular pathways, such as topical JAK-STAT inhibitors, chemokine-inducing oligosaccharide biomaterials, and botanical-derived compounds like Berberine.

[0091] To further support a healthy scalp microenvironment and protect follicular cells from oxidative stress, the composition may additionally comprise a wide range of antioxidants, vitamins, and beneficial plant extracts. To further support a healthy scalp microenvironment and protect follicular cells from oxidative stress, the composition may additionally comprise one or more antioxidants. Non-limiting examples of suitable antioxidants include Vitamin C, Vitamin E, proanthocyanidin, a-lipoic acid, glutathione, coenzyme Q10, resveratrol, curcumin, caffeic acid, ferulic acid, niacinamide, ferulic acid, silymarin, gallic acid and Vitamin B3. Suitable vitamins for inclusion include Vitamin A, Vitamin C, and Vitamin B Complex which may comprise niacinamide (B3), B6, B12, and folic acid. Vitamin B7 (Biotin) is a particularly preferred vitamin. Potent antioxidants may also be included, such as Ergothioneine. The composition may alsoAttorney Docket No. DRIP101WOinclude trace minerals that support hair health, such as selenium, which may be provided in combination with Vitamin E. In various aspects where these antioxidant and vitamin agents are included, their total concentration may range from about 0.1% to about 2.5% by weight of the composition.

[0092] In other aspects, the composition may further comprise one or more advanced bioactive agents to potentiate the regenerative environment of the scalp. These agents can work synergistically with PLA or derivative particles to support follicular health. Non-limiting examples of such bioactive agents include: (a) Growth factors, such as platelet-derived growth factors (PDGF) or those found in platelet-rich plasma (PRP); (b) Polynucleotides (PN) or polydeoxyribonucleotide (PDRN), which are known to enhance fibroblast activity and tissue repair; (c) Peptides and amino acids, which serve as building blocks for hair proteins; (d) Nicotinamide adenine dinucleotide (NAD) boosters and precursors, such as quercetin, Houttuynia cordata and 1-MNA, which support cellular metabolism and resilience; (e) Exosomes, which are nanovesicles that facilitate intercellular communication and can deliver regenerative signals to follicular cells; (f) rapamycin or an equivalent modulator of mammalian target of rapamycin (MTOR) inhibitor; and, (g) Amniotic fluid biologies, which contain a complex mixture of growth factors and anti-inflammatory molecules.

[0093] As used herein, NAD boosters, and precursors, refer to agents that enhance cellular nicotinamide adenine dinucleotide (NAD+) availability. These agents may promote hair growth by increasing NADPH production, which is crucial for antioxidant defense and anabolic processes within follicular cells. Non-limiting examples of NAD boosters include P-nicotinamide mononucleotide (NMN) and botanical extracts known to support NAD+ synthesis, such as quercetin and Houttuynia cordata (e.g., quercitrin).

[0094] The methods of the present disclosure may also be performed as part of a multi-step treatment regimen. In one aspect, the method further comprises a step of applying an additional topical serum to the scalp in conjunction with the microneedling procedure. Such serums may contain the bioactive agents or antioxidants and can be applied after the micro-channels have been created to facilitate their penetration.

[0095] The total concentration of the one or more antioxidants in the composition is selected to be therapeutically effective without compromising the stability of the formulation. In various aspects, the total concentration of antioxidants may be in the range of about 0.1% to about 2.5% by weight of the composition. In other aspects, the concentration may be in a narrower range, such as about 0.1% to 1.5% by weight, or about 0.5% to 1.0% by weight. In certain exemplary aspects, the concentration of the one or more antioxidants is about 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, or 2.5%Attorney Docket No. DRIP101WOby weight.

[0096] The methods of the present disclosure may further encompass a multi-step therapeutic regimen that includes the application of an additional topical serum to the scalp, particularly when used in conjunction with microneedling. The micro-channels created by the microneedling procedure provide a temporary and direct pathway for enhanced delivery of active agents into the dermis.

[0097] In one such aspect, the method comprises the steps of: first, administering the primary PLA or derivative particles composition as described herein; second, performing microneedling on the treated scalp region; and third, applying a separate topical serum to the micro-perforated skin. This topical serum may be formulated to contain bioactive agents that are desired for topical delivery or may not be stable when co-formulated with the injectable PLA or a derivative particles composition. Non-limiting examples of active agents that may be included in this separate topical serum include growth factors, polynucleotides (PN), NAD+ boosters, exosomes, minoxidil, finasteride, or the antioxidants listed previously. This multi-step approach allows for a highly customizable, multi-modal treatment paradigm that leverages the synergistic effects of PLA or a derivative particles bio stimulation, mechanical stimulation from microneedling, and the enhanced delivery of targeted topical agents. The present disclosure is not limited to the foregoing compositions and may further encompass the use of additional topical serums that are applied to the scalp in conjunction with microneedling.

[0098] The primary component of the carrier is a physiologically acceptable aqueous solvent. This solvent provides the volume for the suspension. Non-limiting examples of suitable aqueous solvents include bacteriostatic or deionized water, sterile water for injection, saline (e.g., a 0.9% sodium chloride solution), and buffered saline solutions such as phosphate-buffered saline (PBS).

[0099] A primary excipient in the composition is a gelling agent, also known as a viscositymodifying agent. The primary functions of this agent are to increase the viscosity of the aqueous carrier to form a hydrogel, which serves to keep the PLA or a derivative particle uniformly suspended, prevent their rapid sedimentation, and ensure a smooth and consistent extrusion during injection. Suitable gelling agents are typically cellulose derivatives.

[0100] In one aspect, the gelling agent is carboxymethylcellulose (CMC), such as sodium carboxymethylcellulose. In another aspect, the gelling agent is hydroxypropyl methylcellulose (HPMC). The present disclosure also contemplates the use of analogues and other suitable hydrogel-forming polymers. Non-limiting examples of such agents include methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, ethylhydroxyethylcellulose, hyaluronic acid, poloxamers, and other similar biocompatible polymers known in the art to formAttorney Docket No. DRIP101WOhydrogels.

[0101] The concentration of the gelling agent is selected to achieve a target viscosity that balances suspension stability with injectability. In various aspects, the gelling agent is present in a concentration of about 0.5% to about 4.0% by weight of the composition. In one aspect, the gelling agent is present at a concentration of about .8 to 1 % by weight of the composition.

[0102] The composition may further comprise a bulking agent. In a particular aspect, the bulking agent is mannitol. Other suitable analogues include, but are not limited to, trehalose, sorbitol, and sucrose. In various aspects, the bulking agent is present in a concentration of about 0.5% to about 5% by weight of the composition. In one aspect, the bulking agent is present at a concentration of about 1.2 to 1.4% by weight of the composition.

[0103] The formulations of the present disclosure may be prepared using standard pharmaceutical compounding techniques. In a typical aspect, the components of the formulation, including the PLA or derivative particles, the aqueous carrier, and any selected excipients, are simply combined and mixed in the required amounts to achieve a homogenous suspension.

[0104] Alternatively, a multi-step preparation method may be used. For example, a subset of components, such as a gelling agent and the aqueous carrier, may be premixed to form a stable hydrogel. Subsequently, the PLA or derivative particles and any remaining components can be added to this hydrogel, either simultaneously or sequentially, and mixed until uniformity is achieved. The precise manner of preparing the formulation will depend on the specific PLA or derivative particles and excipients chosen and their desired final concentrations.

[0105] The final concentration of the aqueous carrier, such as bacteriostatic or deionized or sterile water, is a key parameter of the formulation.

[0106] The formulations described herein may also include more than one therapeutic compound, as desired for the particular indication being treated. It is preferable to select compounds with complementary activities that do not adversely interact with each other or compromise the stability of the overall formulation.

[0107] For in vivo administration, particularly via injection, the final formulation must be sterile. Sterility can be achieved by methods well known in the art. For instance, the composition can be prepared using aseptic techniques and its components can be passed through sterile filtration membranes (e.g., a 0.22 pm filter) prior to mixing. Alternatively, terminal sterilization methods such as pasteurization, autoclaving, or gamma irradiation may be employed, provided the chosen method does not adversely affect the physical or chemical properties of the PLLA particles or other formulation components.

[0108] In one aspect, the other components of the composition, excluding the active agent,Attorney Docket No. DRIP101WOincluding pharmaceutically acceptable carriers and excipients, are present at a combined concentration of about 20 mg / mL. In some aspects, the other components of the composition are at a concentration of about 21 mg / mL. In some aspects, the other components of the composition are at a concentration of about 22 mg / mL. In some aspects, the other components of the composition are at a concentration of about 23 mg / mL. In some aspects, the other components of the composition are at a concentration of about 24 mg / mL. In some aspects, the other components of the composition are at a concentration of about 25 mg / mL. In some aspects, the other components of the composition are at a concentration of about 20 to 25 mg / mL. In some aspects, the other components of the composition are at a concentration of about 20 to 23 mg / mL. The ratio of active agents to excipient in these compositions in an aspect is about 1 :5, in another aspect is about 2:5, in another aspect is about 2.5:4.5, in another aspect is about 2.9:4.4, and in another aspect about 1:1.

[0109] In another aspect, the other components of the composition are at a concentration of about 15 to 20 mg / mL, 10 to 15 mg / mL, 5 to 10 mg / mL, or 1 to 5 mg / mL. The ratio of active agents to excipients in these compositions would be about 1:1; 2:1, 3:1, 4:1, or between 4:1 and 15:1. The active agent of the present invention comprises particles of polylactic acid (PLA) or a derivative thereof. As used herein, PLA derivatives include various stereoisomers of polylactic acid, such as poly-L-lactic acid (PLLA), poly-D-lactic acid (PDLA), and poly-D, L-lactic acid (PDLLA), which is a racemic mixture of the L- and D-isomers. The choice of stereoisomer can be used to control the physical properties of the particles, such as their crystallinity and degradation rate. PLLA is a semi-crystalline polymer, while PDLA is its enantiomer. PDLLA is an amorphous polymer and typically degrades more rapidly than its semi-crystalline counterparts.

[0110] In another aspect, the composition comprises particles made substantially of a single stereoisomer, such as PLLA. In another aspect, the composition comprises particles made from a blend of two or more PLA derivatives. For example, a composition may comprise a blend of PLLA and PDLLA particles. By adjusting the ratio of these polymers, the degradation profile and resulting biostimulatory effect of the composition can be precisely tailored. In various aspects, the composition may comprise a PLLA to PDLLA ratio of about 90:10, 80:20, 70:30, 60:40, 50:50 40:60, 30:70, 20:80, or 10:90 by weight.[OHl] In another aspect, a composition comprises about 7.5 mg / mL (approximately .735% by weight), contemplating + / -1.5 mg / mL, of PLA or derivative particles, about 4.5 mg / mL (approximately 0.442 % by weight, or adjusted per "+ / -") of carboxymethylcellulose, and about 6.38 mg / mL (approximately .627 % by weight, or adjusted per "+ / -") of mannitol, all suspended in bacteriostatic or deionized water or sterile water for injection. This results in a total excipientAttorney Docket No. DRIP101WOconcentration of about 10.88 mg / mL (approximately 1.07% by weight or adjusted perThis specific formulation provides a PLA or derivative particles concentration and an excipient profile that is different from prior formulations intended for dermal filling. Accordingly, in all aspects, the compositions of the present disclosure are specifically formulated for administration to the scalp to stimulate hair growth or treat hair loss and are not for the purpose of dermal volume augmentation or wrinkle filling.

[0112] In another aspect, a composition comprises about 15 mg / mL (approximately 1.45% by weight), contemplating + / -1.5 mg / mL, of PLA or derivative particles, about 9 mg / mL (approximately 0.87% by weight, or adjusted per "+ / -") of carboxymethylcellulose, and about 12.75 mg / mL (approximately 1.23% by weight, or adjusted per "+ / -") of mannitol, all suspended in bacteriostatic or deionized water or sterile water for injection. This results in a total excipient concentration of about 21.75 mg / mL (approximately 2.1% by weight or adjusted per "+ / -"). This specific formulation provides a PLA or derivative particles concentration and an excipient profile that is different from prior formulations intended for dermal filling. Accordingly, in all aspects, the compositions of the present disclosure are specifically formulated for administration to the scalp to stimulate hair growth or treat hair loss and are not for the purpose of dermal volume augmentation or wrinkle filling.

[0113] In another aspect, a composition comprises about 30 mg / mL (approximately 2.85% by weight), contemplating + / -1.5 mg / mL, of PLA or derivative particles, about 12.75 mg / mL (approximately 1.21% by weight, or adjusted per "+ / -") of carboxymethylcellulose, and about 12.75 mg / mL (approximately 1.21% by weight, or adjusted per "+ / -") of mannitol, all suspended in bacteriostatic or deionized water or sterile water for injection. This results in a total excipient concentration of about 25.5 mg / mL (approximately 2.42% by weight or adjusted per "+ / -"). This specific formulation provides a PLA or derivative particles concentration and an excipient profile that is different from prior formulations intended for dermal filling. Accordingly, in all aspects, the compositions of the present disclosure are specifically formulated for administration to the scalp to stimulate hair growth or treat hair loss and are not for the purpose of dermal volume augmentation or wrinkle filling.

[0114] In another aspect, a composition comprises about 45 mg / mL (approximately 4.27% by weight), contemplating + / -1.5 mg / mL, of PLA or derivative particles, about 5 mg / mL (approximately 0.47% by weight, or adjusted per "+ / -") of carboxymethylcellulose, and about 5 mg / mL (approximately 0.47% by weight, or adjusted per "+ / -") of mannitol, all suspended in bacteriostatic or deionized water or sterile water for injection. This results in a total excipient concentration of about 10 mg / mL (approximately 0.94% by weight or adjusted per "+ / -"). ThisAttorney Docket No. DRIP101WOspecific formulation provides a PLA or derivative particles concentration and an excipient profile that is different from prior formulations intended for dermal filling. Accordingly, in all aspects, the compositions of the present disclosure are specifically formulated for administration to the scalp to stimulate hair growth or treat hair loss and are not for the purpose of dermal volume augmentation or wrinkle filling.

[0115] In another aspect, the PLA or derivative thereof is at a concentration of about 1.5% (w / v). In some aspects, the PLA or a derivative thereof is at a concentration of about 1.4% (w / v). In some aspects, the PLA or a derivative thereof is at a concentration of about 1.3% (w / v). In some aspects, the PLA or a derivative thereof is at a concentration of about 1.2% (w / v). In some aspects, the PLA or a derivative thereof is at a concentration of about 1.1% (w / v). In some aspects, the PLA or a derivative thereof is at a concentration of about 1.0% (w / v). In some aspects, the PLA or a derivative thereof is at a concentration of about 1.0% to 1.5% (w / v). In some aspects, the PLA or a derivative thereof is at a concentration of below 1.0% (w / v).

[0116] Table 1 shows non-limiting formulations of the compositions described herein:Table 1:

[0117] In another aspect, the compositions described herein comprises about 1.5% (w / v) PLA or a derivative thereof (e.g., PLLA (w / v)), about 0.9% carboxymethylcellulose (e.g., sodium carboxymethylcellulose (CMC)), and 1.3% of mannitol (e.g., nonpyrogenic mannitol). In certain aspects, the compositions described herein comprises between 1.2% and 1.6% PLA or a derivative thereof (e.g., PLLA) (w / v), and between 2.1 and 2.2% excipient (w / v). In certain aspects, the compositions described herein comprise lower than 1.5 % PLA or a derivative thereof (e.g., PLLA) (w / v), and less than 2.2% excipient (w / v). In some aspects, excipients carboxymethylcellulose and mannitol are inert ingredients and may promote stability of the microparticles as well as swelling mitigation after injection.

[0118] In other aspects, the compositions described herein may be used alone or in combinationAttorney Docket No. DRIP101WOwith one or more adjunctive hair-restoration modalities. Such combination approaches may enhance follicular stimulation, improve dermal penetration, or potentiate the biological activity of the administered composition. The combinations may be performed sequentially, concurrently, or according to any clinically appropriate schedule.

[0119] In a primary aspect of the disclosure, the compositions are specifically formulated for administration by injection, including subcutaneous, intradermal, deep dermal, mid-dermal, and subdermal delivery. A key technical consideration in formulating the composition is its nature as a suspension of particles, which presents unique challenges for injectability compared to a simple solution. Accordingly, the formulation is prepared to have specific physical properties to ensure consistent, reliable, and uniform delivery through a fine-gauge needle, a cannula, or the microneedles of a delivery device as described herein.

[0120] These physical properties include optimized viscosity, stability, and particle characteristics. They include pharmaceutically acceptable excipients such as viscosity -modifying agents (e.g., carboxymethylcellulose, hyaluronic acid), tonicity agents, and stabilizers that ensure both the physical stability of the suspension and its suitability for injection. The particle size of the PLA or a derivative thereof (e.g., PLLA) is also controlled to be significantly smaller than the inner diameter of the intended delivery apparatus to prevent clogging.

[0121] In other aspects, the compositions described herein may be formulated for topical use, particularly in conjunction with a microneedling procedure. In this configuration, the composition may be applied to the scalp as a glide medium during microneedling, allowing the PLA or a derivative thereof (e.g., PLLA) particles to penetrate the micro-channels created by the needles. Alternatively, the composition may be applied as a topical serum after the microneedling procedure is complete, taking advantage of the temporarily increased permeability of the skin to deliver the PLA or a derivative thereof (e.g., PLLA) particles into the dermis. For such topical applications, the formulation may have a different viscosity profile, optimized for surface application and penetration rather than for the specific rheological demands of injection.

[0122] In some aspects, the compositions described herein are not for dermal volume augmentation or wrinkle filling.

[0123] In some aspects, transdermal delivery of the compositions described herein may be enhanced by a variety of means. For example, the formulation may also include penetrants including either or both chemical penetrants (CPEs) and peptide-based cellular penetrating agents (CPPs) to facilitate passage through the skin barrier. Alternatively, transdermal delivery may be improved by mechanically disrupting the surface of the skin, such as by microneedles, dermabrasion, or other methods that create microchannels. In other aspects, the composition mayAttorney Docket No. DRIP101WOsimply be applied under an occlusive patch to increase absorption through the stratum comeum. These approaches may be used alone or in combination to optimize delivery of the active agent to target tissues.

[0124] The compositions and methods described herein alter the scalp's microenvironment, which is critical for healthy follicular function. As skin ages or is damaged, the dermis can undergo atrophy, leading to a reduction in structural components like collagen and elastin. Dermal atrophy on the scalp can compromise integrity of the hair follicle roots and associated structures, such as dermal papilla and hair follicle bulges. In response to administration of PLA or derivative particles composition as described, a localized regenerative response is initiated, which can promote extracellular matrix remodeling and increases in the density of structural proteins. This rejuvenation of the scalp dermis can counteract atrophy, creating a healthier and more robust environment for hair follicles. Improved dermal structure provides better physical support and vascular supply to the hair follicle roots, supporting healthier and more resilient follicular function and promoting the growth of hair.

[0125] The pH of the formulation is selected to ensure biocompatibility and minimize injection site reactions. The physiological pH of the dermal and subdermal tissue is approximately 7.4. Injectable formulations with a pH close to this physiological neutral value are generally preferred.

[0126] Accordingly, in various aspects, the composition is formulated to have a pH in a range of about 4.5 to about 8.5 in comprising bacteriostatic or deionized water. Bacteriostatic water contains .9% benzyl alcohol. In some aspects, to better balance stability and patient comfort, the pH is in a range of about 6.0 to about 8.0. In other aspects, the pH is between about 6.5 and 7.5. In an aspect thereof, the final pH of the composition is adjusted to be substantially physiologically neutral, for example, about 7.0 to about 7.4. In one aspect the presence of lidocaine in the bacteriostatic or deionized water provides an acidic range between 5 and 6.5.

[0127] The desired pH of the composition may be achieved and maintained using one or more pharmaceutically acceptable buffering agents known in the art. Non-limiting examples of suitable buffers include, but are not limited to, phosphate buffers (e.g., phosphate-buffered saline or PBS), citrate buffers, acetate buffers, or Tris buffers. The buffering agent is included in a concentration sufficient to maintain the pH of the composition within the desired range during storage and administration.

[0128] The pH of the therapeutic composition is carefully controlled to ensure the stability of the active agent, the biocompatibility of the formulation, and the comfort of the subject upon administration. The selection of an appropriate pH range balances the chemical stability of the PLA or derivatives thereof (PLLA) particle with the physiological requirements of the target tissue. PLAAttorney Docket No. DRIP101WOor derivatives thereof (PLLA) particle, as a polyester, is susceptible to degradation via hydrolysis. This degradation process is known to be catalyzed by both acidic and alkaline conditions. In some aspects pH may be adjusted to facilitate hydrolysis. In some aspects, it may be desirable to adjust the pH of the compositions PLA or derivatives thereof (PLLA) particle compositions herein to facilitate permeation or to modulate the properties of the target compounds in the subject or on the applied device. In certain instances, the pH may be adjusted to a range of about 9-11, or more specifically about 10-11, using appropriate buffering agents or by direct addition of a suitable acid or base.

[0129] A formulation can include other components that act as excipients or serve purposes other than for promoting hair growth. For example, preservatives like antioxidants (e.g., ascorbic acid or a-lipoic acid) and anti-inflammatory agents may be included. Other components apart from therapeutically active ingredients and components that are the primary effectors of dermal penetration may include those provided for aesthetic purposes such as menthol or other aromatics, and components that affect the physical state of the composition such as emulsifiers, for example, Durosoft®. Typically, these ingredients are present in very small percentages of the compositions. It is understood that these latter ancillary agents are neither therapeutic ingredients nor are they components that are primarily responsible for penetration of the skin. The components that primarily affect skin penetration have been detailed as described above.

[0130] The formulation can also include alternative gelling components. Suitable alternative gelling components may include but are not limited to isopropyl palmitate, ethyl laurate, ethyl myristate and isopropyl myristate. In some aspects, the gelling component in the composition is at a concentration of about 1 to 10% (v / v). In some aspects, the formulation includes Siligel™ at a concentration of about 1 to 5% (w / v) or about 5 to 15% (w / v) or an equivalent mixture of xanthan gum, sclerotium gum, and pullulan. In some aspects, the formulation may include a mixture of caprylic triglycerides and capric triglycerides in an amount of less than about 2%, 8%, or 10% (w / v) of the total formulation. In certain aspects, the formulation may include Myritol® 312 at a concentration of about 0.5-10% (w / w), or an equivalent mixture of caprylic and capric triglycerides.

[0131] In some aspects, an additional component of the formulations described herein may be an alcohol, such as benzyl alcohol or related aromatic alcohols. The alcohol may be present at a concentration of about 0.5-20% (v / v) of the total composition, including intermediate concentrations such as 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% (v / v), or any other concentration within this range.

[0132] The formulation described in this specification may also include more than oneAttorney Docket No. DRIP101WOtherapeutic compound as desired for the particular indication being treated, preferably those with complementary activities that do not adversely affect the other proteins. A formulation to be used for in vivo administration can be sterile. This can be accomplished, for instance, without limitation, by filtration through sterile filtration membranes, prior to, or following, preparation of a formulation or other methods known in the art, including, without limitation, pasteurization.

[0133] A formulation of the disclosure may be prepared in several ways. Typically, the components of a formulation are simply mixed in the required amounts.

[0134] Alternatively, some subsets of these components can first be mixed and then "topped off with the remaining components either simultaneously or sequentially. The precise manner of preparing a formulation will depend on the choice of carbonates and the percentages of the remaining components that are desirable with respect to that carbonate salt. In some aspects, the water is in an amount between about 10-85% (w / w), 15-50 % (w / w), or 15-45 % (w / w) of the formulation

[0135] In another aspect, formulations of the disclosure can be administered or co- administered with one or more additional agents that promote hair growth. For example, the formulation can be co-administered with finasteride, minoxidil, dutasteride, spironolactone, platelet-rich plasma (PRP) or topical steroids.

[0136] In some aspects, the present disclosure features methods for promoting hair growth or treating hair loss in a subject in need thereof. In some aspects, the method comprises administering a composition as described herein. For example, the composition may comprise: PLA or a derivative thereof (e.g., PLLA, PDLA, or PDLLA) in a pharmaceutically acceptable carrier. In other aspects, the method involves administering a composition comprising poly-L-lactic acid (PLLA) and a pharmaceutically acceptable carrier. In some aspects, the methods further comprise microneedling.

[0137] A key feature of the disclosed methods is the targeted administration of PLA or a derivative thereof (e.g., PLLA, PDLA, or PDLLA) composition to a specific depth within the skin of the scalp. The objective is to deliver the PLA or derivative particles directly to the anatomical region of the hair follicle that is critical for hair growth and regeneration. As illustrated in Figure 3A of skin layers, the hair follicle is a complex structure that extends from the Epidermis down through the Dermis and into the Hypodermis (also known as the subcutaneous fat layer). The regenerative components of the follicle, including the hair follicle bulge stem cells and the dermal papilla, are located deep within the dermis and near the dermal-hypodermal junction.

[0138] To achieve the desired biostimulatory effect, the composition is administered to a depth sufficient to reach these key follicular structures. Incorrect injection depth or angle of insertion canAttorney Docket No. DRIP101WOlead to alopecia. In various aspects, the composition is delivered into the Dermis, a practice referred to as intradermal administration. In other aspects, the composition is delivered into the Hypodermis, which may be referred to as hypodermal or subcutaneous administration. As used herein, the term "subdermal administration" broadly refers to delivering the composition to a plane beneath the epidermis, encompassing delivery into the mid-dermis, deep dermis, and / or the upper portion of the hypodermis, to ensure the PLLA particles are placed in proximity to the hair follicle bulge and bulb.

[0139] While the optimal depth can be defined by the targeted anatomical layer, it can also be described by a numerical depth of administration. Figure 3B indicates experimentation leading to one aspect demonstrating the injection technique on a cadaver. The thickness of the scalp skin can vary depending on the individual and the specific location on the head. Accordingly, in some aspects, the composition is administered to a depth of about 1 mm to about 8 mm. In some aspects, the depth of administration is between about 2 mm and about 6 mm. In a particular aspect, the composition is administered to a depth of about 3 mm to 5 mm, which has been found to be highly effective for targeting the hair follicle bulge and associated regenerative structures in most subj ects.

[0140] Administration of PLLA particles to a targeted depth in the scalp differs over the prior art. Compositions intended for superficial cosmetic effects remain in the epidermis or superficial dermis, while prior art PLLA fillers are often placed for bulk volume in the deep dermis or subcutaneous fat without specific targeting of follicular structures. The methods of the present disclosure, by contrast, teach the intentional and precise placement of the uniquely formulated PLLA composition into the deep dermal and subdermal planes that house the regenerative machinery of the hair follicle, thereby initiating a targeted biostimulatory response stimulating hair growth.

[0141] The methods of the present disclosure involve the administration of the therapeutic PLLA compositions described herein to the scalp of a subject to treat hair loss or stimulate hair growth. Administration is performed in a manner that ensures the targeted and effective delivery of the PLLA particles to the regenerative structures of the hair follicle.

[0142] In various aspects, the composition is administered via injection into or beneath the skin. Suitable routes of administration include, but are not limited to, transdermal, intradermal, subdermal, or subcutaneous injection. The primary target for administration is tissue on the scalp associated with hair follicles.

[0143] In various aspects, the composition is administered to a depth of about 1 mm to 8 mm. In a particular aspect, the depth is between about 2 mm and 6 mm. In some aspect, the composition is administered at a depth of about 3 mm to 5 mm, which has been found to be highly effective forAttorney Docket No. DRIP101WOreaching the hair follicle bulge stem cells in most subjects.

[0144] In some aspects, the composition is administered at a depth sufficient to reach the hair follicle bulb (e.g., about 5 to 6 mm). For example, in some aspects, the composition is administered at a depth of about 2 to 5 mm or about 2 to 6 mm. In some aspects, the composition is administered at a depth of about 3 to 5 mm. In some aspects, the composition is administered at a depth of about 3 to 6 mm. In some aspects, the composition is administered at a depth of about 1 to 8 mm, about 1 to 7, about 1 to 6 mm, about 1 to 5 mm, about 1 to 4 mm, about 1 to 3 mm, or about 1 to 2 mm. However, the present disclosure is not limited to the injection depths, and the exact depth may be adjusted based on the subject, injection site, and method of administration to optimize follicular delivery. Incorrect depth of injection can lead to alopecia.

[0145] The angle of administration may be adjusted to accommodate patient anatomy and optimize comfort and delivery. In some aspects, the composition is administered at an angle of about 10° to 90° relative to the skin surface. In one aspect as determined through experimentation as in Figure 3B, the composition is administered at a shallower angle to facilitate placement in the correct subdermal plane, for example, at an angle of about 10° to 30°, and more preferably at an angle of about 15° to 20° relative to the skin surface. Without wishing to limit the present disclosure to any theory or mechanism it is believed that treatment efficacy is independent of the injection angle. The angle of administration may be adjusted as needed to accommodate patient anatomy and optimize comfort. Incorrect plane due to incorrect angle of injection can lead to alopecia.

[0146] The total volume and dosage of the PLLA composition administered per treatment session can be adjusted based on the extent of hair loss and the size of the treatment area. In some aspects, a total volume of about 5 mL to 15 mL of the composition is administered across all sites on the scalp, with a favored total volume being about 8 mL to 12 mL. In another aspect, a total of about 10 mL of the composition is administered per session. The concentration of PLLA administered at these volumes is at a concentration of about 14 to 16 mg / mL.

[0147] In some aspects, the composition is administered transdermally, intradermally, or via a subcutaneous injection. In certain aspects, the composition is administered by an injection (e.g., intradermal injection) at one or more sites of the scalp. For example, the composition may be administered to tissue associated with hair follicles. In some aspects, the composition is administered at or near a hair follicle. In certain aspects, the composition is administered at or near hair follicle bulge stem cells.

[0148] In some aspects, the composition is administered using a single introduction site followed by multiple retrograde linear passes with a cannula to distribute the formulation throughout the targeted region. In certain aspects, a single-entry point is created using a guide needle for eachAttorney Docket No. DRIP101WOtreatment site. Thereafter, a cannula is introduced through the guide entry point and advanced using a fanning technique to disperse a uniform amount of the composition across the treatment area. In some aspects, this method enables controlled, even placement of the formulation while reducing the number of skin punctures and improving patient comfort.

[0149] In some aspects, the composition may be administered using any cannula suitable for precise delivery, including cannulas of varying lengths and diameters. In some aspects, the composition is administered with a blunt-tip cannula. In certain aspects, the blunt tip cannula may have various gauges, for example, 23G, collage, or 27G and its length may be selected based on the treatment site and tissue depths. In some aspects, a 1.5 inch (38 mm) blunt tip cannula is used. In other aspects, a 36 mm blunt tip cannula is used. The present disclosure is not limited to a particular gauge or length; one of ordinary skill in the art may select a cannula of suitable size depending on the treatment site and depth required for the methods described herein. Additionally, other cannula types suitable for administering the composition may also be used in accordance with the methods of the disclosure.

[0150] In some aspects, the composition is administered at a depth sufficient to reach the hair follicle bulb (e.g., about 5 to 6 mm). For example, in some aspects, the composition is administered at a depth of about 2 to 5 mm or about 2 to 6 mm. In some aspects, the composition is administered at a depth of about 3 to 5 mm. In some aspects, the composition is administered at a depth of about 3 to 6 mm. In some aspects, the composition is administered at a depth of about 1 to 8 mm, about 1 to 7, about 1 to 6 mm, about 1 to 5 mm, about 1 to 4 mm, about 1 to 3 mm, or about 1 to 2 mm. However, the present disclosure is not limited to the injection depths, and the exact depth may be adjusted based on the subject, injection site, and method of administration to optimize follicular delivery.

[0151] In some aspects, the composition is administered at an angle of about 15 to 20° relative to the skin surface. In some aspects, the composition is administered at an angle of about 10 to 30° relative to the skin surface. In some aspects, the composition is administered at an angle of about 15 to 25° relative to the skin surface. In some aspects, the composition is administered at an angle of about 10 to 20° relative to the skin surface. In some aspects, the composition is administered at an angle of about 10 to 30° relative to the skin surface. In some aspects, the composition is administered at an angle of about 10 to 45° relative to the skin surface. In some aspects, the composition is administered at an angle of about 10 to 90° relative to the skin surface. In some aspects, the composition is administered at an angle of about 45 to 90° relative to the skin surface. Without wishing to limit the present disclosure to any theory or mechanism it is believed that treatment efficacy is independent of the injection angle. The angle of administration may beAttorney Docket No. DRIP101WOadjusted as needed to accommodate patient anatomy and optimize comfort.

[0152] In some aspects, about 5 to 20 mg of PLA or a derivative thereof (e.g., PLLA) is administered at each of the one or more sites. In other aspects, about 5 to 15 mg of PLA or a derivative thereof (e.g., PLLA) is administered at each of the one or more sites. In some aspects, about 10 to 20 mg of PLA or a derivative thereof (e.g., PLLA) is administered at each of the one or more sites. In other aspects, about 10 to 15 mg of PLA or a derivative thereof (e.g., PLLA) is administered at each of the one or more sites. In certain aspects, about 15 mg of PLA or a derivative thereof (e.g., PLLA) is administered at each of the one or more sites.

[0153] In some aspects, a total of about 10 mLs of the composition is administered across the one or more sites of the scalp treatment sites. In some aspects, a total of about 8 mLs of the composition is administered across the one or more sites of the scalp treatment sites. In some aspects, a total of about 5 mLs of the composition is administered across the one or more sites of the scalp treatment sites. In some aspects, a total of about 12 mLs of the composition is administered across the one or more scalp treatment sites. In some aspects, a total of about 15 mLs of the composition is administered across the one or more sites of the scalp treatment sites. In some aspects, a total of about 5 to 15 mLs of the composition is administered across the one or more scalp treatment sites. In some aspects, a total of about 8 to 12 mLs of the composition is administered across the one or more scalp treatment sites. However, the present disclosure is not limited to the volumes and may also include other suitable volumes, as determined by the extent of hair loss and the specific treatment areas.

[0154] In some aspects, the composition is administered in region-specific volumes to optimize coverage of the targeted scalp areas. For example, in certain aspects, about 1 to 5 mLs of the composition are administered to each temporal region. In some aspects, about 2 to 4 mLs of the composition are administered to each temporal region. In some aspects, about 3 mLs of the composition are administered to each temporal region. In some aspects, about 2 mLs of the composition are administered to each temporal region. In some aspects, about 4 mLs of the composition are administered to each temporal region. In other aspects, about 2 to 6 mLs are administered to the frontal midline region. In other aspects, about 3 to 10 mLs of the composition are administered to each temporal region. In other aspects, about 5 to 15 mLs of the composition are administered to each temporal region. This total volume may be distributed in region-specific volumes to optimize coverage. For example, in certain aspects, about 1 mL to 5 mL of the composition is administered to each temporal region, and about 2 mL to 6 mL is administered to the frontal midline region. The administration is not limited to these regions and may include any scalp area showing hair loss, such as the crown or parietal ridge. In some aspects, about 3 to 5 mLsAttorney Docket No. DRIP101WOare administered to the frontal midline region. In some aspects, about 4 mLs are administered to the frontal midline region. In some aspects, about 5 mLs are administered to the frontal midline region. In some aspects, about 3 mLs are administered to the frontal midline region. For example, in certain aspects, about 1 mL to 5 mL of the composition is administered to each temporal region, and about 2 mL to 6 mL is administered to the frontal midline region. In other aspects, about 3 to 10 mLs of the composition are administered to the frontal midline. In other aspects, about 5 to 15 mLs of the composition are administered to the frontal midline. The administration is not limited to these regions and may include any scalp area showing hair loss, such as the crown or parietal ridge. The present disclosure is not limited to the specifically mentioned regions and may include any scalp regions showing hair loss, such as the crown and parietal ridge. In some aspects, the total volume per treatment session may be adjusted based on the extent of thinning, scalp anatomy, or clinical judgment.

[0155] In some aspects, the methods comprise administering one or more doses of the composition described herein to a subject. In certain aspects, the methods include administering at least two doses of the composition. In some aspects, the methods comprise administering two or more doses of the composition described herein to a subject. In some aspects, the methods comprise administering three or more doses of the composition described herein to a subject. In some aspects, the methods comprise administering four or more doses of the composition described herein to a subject. The doses may be administered at intervals of about 4 to 6 weeks. In some aspects the doses may be administered at 8 to 12 weeks. In some aspects the doses may be administered at 14-24 weeks. In some aspects, the doses may be administered at intervals of about 2 to 4 weeks. The present disclosure is not limited to the administration intervals, and the dosing schedule may be adjusted based on patient response. In some aspects, subsequent doses may be administered to the same regions of the scalp or to different areas to further enhance hair growth and coverage.

[0156] In one aspect of the method, a subject receives two treatment sessions spaced approximately 4 to 6 weeks apart. In some aspects the doses may be administered at 8 to 12 weeks. In some aspects the doses may be administered at 14-24 weeks. Prior to administration, local anesthesia may be achieved, for example by injecting 1% lidocaine into the treatment zone. The PLLA composition is then administered into the deep dermis, at a depth of approximately 3 mm to 5 mm, to target the anatomic location of the hair follicle bulge and dermal papilla.

[0157] In one aspect, the composition is administered via a 25-gauge, 1.5-inch blunt-tip cannula. Within each treatment zone, the product is distributed radially around a pre-marked point to encompass an approximate area of 2 cm x 2 cm. During each session, a volume of approximatelyAttorney Docket No. DRIP101WO3 mL of the composition is injected into each temporal zone, and approximately 4 mL is injected into the frontal midline zone, for a total volume of about 10 mL per session. Following injection, subjects may massage treated areas for a period, such as one week, to promote even product distribution.

[0158] In certain aspects, the compositions described herein may be used alone or in combination with one or more adjunctive hair-restoration modalities. Such combination approaches may enhance follicular stimulation, improve dermal penetration, or potentiate the biological activity of the administered composition. The combinations may be performed sequentially, concurrently, or according to any clinically appropriate schedule. For example, in some aspects, the methods described herein may further comprise ministering one or more additional medicaments, e.g., finasteride, minoxidil, spironolactone, platelet-rich plasma (PRP), or topical steroids.

[0159] The efficacy of the treatment can be assessed by measuring these hair attributes at one or more time points following administration of the composition and comparing them to baseline measurements taken from the same scalp region prior to treatment. In certain embodiments or aspects, improvements in hair attributes are observed at about six months after administration. In other aspects, such improvements may be evaluated at time points between about six and eight months, or between about six and twelve months, following the initiation of treatment, as the biostimulatory effects of PLLA particles can manifest progressively over time.

[0160] The methods described herein may comprise administering one or more doses of the composition to a subject over a course of treatment. In one aspect, a subject receives at least two treatment sessions. For example, a treatment course may comprise two, three, or four doses. These doses are typically administered at intervals of about 2 to 6 weeks. In one aspect, the doses are administered at intervals of about 4 to 6 weeks. The dosing schedule can be adjusted by a clinician based on patient response, and subsequent doses may be administered to the same or different regions of the scalp to further enhance hair growth.

[0161] The administration of the compositions and the performance of the methods described herein result in improvement in health and appearance of the hair and scalp. The primary therapeutic outcome is the stimulation of hair growth and the treatment of hair loss conditions such as alopecia. This outcome can be quantified by measuring the change in one or more hair attributes.

[0162] In various aspects, administration of the composition to the scalp results in a measurable increase in hair thickness, which can be observed as an increase in the mean fiber diameter of individual hair shafts. In other aspects, the treatment results in an increase in hair length over a defined period. In further aspects, the treatment can lead to an increase in hair pigmentation, resulting in darker, more richly colored hair.Attorney Docket No. DRIP101WO

[0163] Additional non-limiting hair attributes that are improved by the present disclosure include an increase in hair density (measured, for example, as hairs per cm2), an improvement in follicular unit composition (e.g., an increase in the proportion of follicular units containing multiple hair shafts), an improvement in the terminal-to-vellus hair ratio (indicating a shift from fine, miniaturized vellus hairs to thick, mature terminal hairs), and a decrease in the interfollicular distance.

[0164] To demonstrate the efficacy and safety of the methods and compositions described herein, an exemplary clinical study was conducted involving female subjects with clinically diagnosed, stable female pattern hair loss (FPHL). The study employed an intra-patient control design, wherein three predefined areas of thinning, the frontal midline and bilateral temporal regions, were treated while a posterior mid-scalp area served as an untreated control. Each subject received two treatment sessions, spaced 4-6 weeks apart, during which a freshly reconstituted PLLA composition was administered. A subset of patients received adjunctive microneedling with either platelet-derived growth factors (PDGF) or polynucleotides (PN) immediately following the PLLA injection. Clinical outcomes were documented using standardized photography and assessments at follow-up visits conducted at post-treatment. 5 patients from the study are discussed herein.

[0165] Hair metrics were quantified using the HairMetrix® VISIOMED D200EVO dermatoscope (Canfield Scientific, Parsippany, NJ, USA) and its associated software. Parameters included hair density, (hairs / cm2), mean fiber diameter (pm), follicular unit composition, terminal-to-vellus hair ratio, and interfollicular distance. Standardized 2D photographs were captured at each in-person visit (superior, lateral, crown, and parted views) with a digital single-lens reflex camera under consistent lighting and positioning conditions. Patient satisfaction, perceived efficacy, and hair-related confidence were evaluated with structured questionnaires, including the Hair-Q Satisfaction Questionnaire and a Hair Life Quality Index. Responses were collected at each visit. Safety evaluations were conducted at each visit, including documentation of local side effects (erythema, edema, bruising, tenderness, nodules, and irregular product dispersion) and systemic symptoms.

[0166] Figure 4a provides percentages for patient 1 based on HairMetrix®, relative to each visit, and are calculated relative to zone as between each visit and incorporated into a Table, additionally comparing to control zone of injection. Figure 4b indicates raw numbers for patient 1 plotted as a bar graph for each site of injection. Figure 4b indicates for patient 1 of the study, HairMetrix® at the Control Site: Large Terminal Hair decrease from Visit 1 to Visit 3, Intermediate Terminal Hair decrease from Visit 1 to Visit 3, Small Terminal Hair reduction from Visit 1 to Visit 3, Vellus (Miniaturized) Hair increase from Visit 1 to Visit 3; Frontal Midline Site: Large Terminal HairAttorney Docket No. DRIP101WOincrease from Visit 1 to Visit 3, Intermediate Terminal Hair decrease from Visit 1 to Visit 3, Small Terminal Hair increase from Visit 1 to Visit 3, Vellus (Miniaturized) Hair no difference between Visit 1 and Visit 3; The Right Parietal Site: Large Terminal Hair no difference between Visit 1 and Visit 3, Intermediate Terminal Hair no difference from Visit 1 to Visit 3, Small Terminal Hair increase from Visit 1 to Visit 3, Vellus (Miniaturized) Hair increase from Visit 1 to Visit 3; and, Left Parietal Site: Large Terminal Hair no difference between Visit 1 and Visit 3, Intermediate Terminal Hair increase from Visit 1 to Visit 3, Small Terminal Hair increase from Visit 1 to Visit 3, Vellus (Miniaturized) Hair slight increase from Visit 1 to Visit 3. Percentages for patient 1 based on HairMetrix® are provided, relative to each visit, and are calculated relative to zone as between each visit and incorporated into a Table as compared to control.

[0167] Figure 5a provides percentages for patient 2 based on HairMetrix®, relative to each visit, and are calculated relative to zone as between each visit and incorporated into a Table, additionally comparing to control zone of injection. Figure 5b indicates raw numbers for patient 2 plotted as a bar graph for each site of injection. Figure 5b indicates for patient 2 of the study, HairMetrix® at the Control Site: Large Terminal Hair increase from Visit 1 to Visit 3, Intermediate Terminal Hair increase from Visit 1 to Visit 3, Small Terminal Hair no difference from Visit 1 to Visit 3, Vellus (Miniaturized) Hair no difference from Visit 1 to Visit 3; Frontal Midline Site: Large Terminal Hair decrease from Visit 1 to Visit 3, Intermediate Terminal Hair increase from Visit 1 to Visit 3, Small Terminal Hair no difference from Visit 1 to Visit 3, Vellus (Miniaturized) Hair increase between Visit 1 and Visit 3; The Right Parietal Site: Large Terminal Hair decrease between Visit 1 and Visit 3, Intermediate Terminal Hair increase from Visit 1 to Visit 3, Small Terminal Hair slight increase from Visit 1 to Visit 3, Vellus (Miniaturized) Hair no difference Visit 1 to Visit 3; and, Left Parietal Site: Large Terminal Hair no difference between Visit 1 and Visit 3, Intermediate Terminal Hair increase from Visit 1 to Visit 3, Small Terminal Hair increase from Visit 1 to Visit 3, Vellus (Miniaturized) Hair slight increase from Visit 1 to Visit 3.

[0168] Figure 6a provides percentages for patient 3 based on HairMetrix®, relative to each visit, and are calculated relative to zone as between each visit and incorporated into a Table, additionally comparing to control zone of injection. Figure 6b indicates raw numbers for patient 3 plotted as a bar graph for each site of injection. Figure 6b indicates for patient 3 of the study, HairMetrix® at the Control Site: Large Terminal Hair slight increase from Visit 1 to Visit 2, Intermediate Terminal Hair decrease from Visit 1 to Visit 2, Small Terminal Hair no difference from Visit 1 to Visit 2, Vellus (Miniaturized) Hair no difference from Visit 1 to Visit 2; Frontal Midline Site: Large Terminal Hair increase from Visit 1 to Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 2, Small Terminal Hair no difference from Visit 1 to Visit 2, Vellus (Miniaturized) HairAttorney Docket No. DRIP101WOno difference between Visit 1 and Visit 2; The Right Parietal Site: Large Terminal Hair decrease between Visit 1 and Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 2, Small Terminal Hair increase from Visit 1 to Visit 2, Vellus (Miniaturized) Hair no difference from Visit 1 to Visit 2; and, Left Parietal Site: Large Terminal Hair increase between Visit 1 and Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 2, Small Terminal Hair increase from Visit 1 to Visit 2, Vellus (Miniaturized) Hair increase from Visit 1 to Visit 2.

[0169] Figure 7a provides percentages for patient 4 based on HairMetrix®, relative to each visit, and are calculated relative to zone as between each visit and incorporated into a Table, additionally comparing to control zone of injection. Figure 7b indicates raw numbers for patient 4 plotted as a bar graph for each site of injection. Figure 7b indicates for patient 4 of the study, HairMetrix® at the Control Site: Large Terminal Hair increase from Visit 1 to Visit 2, Intermediate Terminal Hair reduction from Visit 1 to Visit 2, Small Terminal Hair reduction from Visit 1 to Visit 2, Vellus (Miniaturized) Hair slight increase from Visit 1 to Visit 2; Frontal Midline Site: Large Terminal Hair decrease from Visit 1 to Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 2, Small Terminal Hair increase from Visit 1 to Visit 2, Vellus (Miniaturized) Hair no difference between Visit 1 and Visit 2; The Right Parietal Site: Large Terminal Hair increase between Visit 1 and Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 3, Small Terminal Hair slight increase from Visit 1 to Visit 2, Vellus (Miniaturized) Hair large increase from Visit 1 to Visit 2; and, Left Parietal Site: Large Terminal Hair no difference between Visit 1 and Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 2, Small Terminal Hair large increase from Visit 1 to Visit 2, Vellus (Miniaturized) Hair slight decrease from Visit 1 to Visit 2.

[0170] Figure 8a provides percentages for patient 5 based on HairMetrix®, relative to each visit, and are calculated relative to zone as between each visit and incorporated into a Table, additionally comparing to control zone of injection. Figure 8b indicates raw numbers for patient 5 plotted as a bar graph for each site of injection. Figure 8b provides percentages for patient 5 based on HairMetrix® are provided, relative to each visit, and are calculated relative to zone as between each visit and incorporated into a Table, additionally comparing to control zone of injection. Figure 8B indicates raw numbers for patient 5 plotted as a bar graph for each site of injection. Figure 8B indicates for patient 5 of the study, HairMetrix® at the Control Site: Large Terminal Hair slight increase from Visit 1 to Visit 2, Intermediate Terminal Hair decrease from Visit 1 to Visit 2, Small Terminal Hair increase from Visit 1 to Visit 2, Vellus (Miniaturized) Hair decrease from Visit 1 to Visit 2; Frontal Midline Site: Large Terminal Hair decrease from Visit 1 to Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 2, Small Terminal Hair increase from Visit 1 to Visit 2, Vellus (Miniaturized) Hair decrease between Visit 1 and Visit 2; The Right Parietal Site: LargeAttorney Docket No. DRIP101WOTerminal Hair decrease between Visit 1 and Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 2, Small Terminal Hair increase from Visit 1 to Visit 2, Vellus (Miniaturized) Hair increase from Visit 1 to Visit 2; and, Left Parietal Site: Large Terminal Hair increase between Visit 1 and Visit 2, Intermediate Terminal Hair increase from Visit 1 to Visit 2, Small Terminal Hair no difference from Visit 1 to Visit 3, Vellus (Miniaturized) Hair slight increase from Visit 1 to Visit 2.

[0171] Results from are summarized for each patient with respect to Figure 4a, Figure 5a, Figure 6a, Figure 7a, and Figure 8a per visit where % change is given as between Visit 1 and Visit 2 as well as between Visit 1 and Visit 3 for the four (4) regions of injection. These values were calculated from images in Figure 4b, Figure 5b, Figure 6b, Figure 7b, and Figure 8b, respectively. Further, for the four (4) hair categories provided as output by HairMetrix®, there are individualized percentage changes calculated, as well as summaries across all four (4) hair categories: Large Terminal Hair, Intermediate Terminal Hair, Small Terminal Hair and Vellus (Miniaturized) Hair based on the photos by the bar graphs present in Figures 4b, 5b, 6b, 7b, and 8b. In Figure 4a the left-parietal and right parietal zones showed summary percentage increases across hair types over percentage increases in the control zone. In Figure 5a there were summary percentage increases in the left parietal zones at both Visit 2 and Visit 3 over the control zone. In Figure 6a there were summary percentage increases in the frontal zone, as well as in the right and left parietal greater than percentage increases in the control zone. In Figure 7a, there were percentage increases in all three test zones over the percentage increases in the control zone at Visit 2 as compared to Visit 1. In Figure 8a there were percentage increases in all test zones over control percentage increases in the control zone from Visit 2 over Visit 1. Different patients from the same trials where quantification was performed are provided in Figures 9a-9e. Before photos are on the left and after photos are on the right for treatments provided in a similar fashion as in Figures 4-8, indicating qualitative increases in hair growth before and after treatment with compositions of PLLA according to the aspects of the disclosure.Additional Aspects

[0172] In some aspects, administering the composition to the scalp results in an increase in one or more hair attributes including but not limited to hair length, thickness and pigmentation. Additional non-limiting hair attributes that may be measured may include hair density, mean fiber diameter, follicular unit composition, terminal to vellus hair ratio and interfollicular distance. In certain aspects, these hair attributes may be measured both prior to and following treatment with a composition described herein, for example, six months after administration. Improvements in hair attributes may be determined by comparing measurements taken before treatment to those obtainedAttorney Docket No. DRIP101WOafter treatment in the same region of the scalp. For example, improvements in hair attributes may be assessed about six months after treatment. In other aspects, such improvements may be evaluated between about six and eight months, or between about six and twelve months, following administration of the composition.

[0173] In aspects, the improves the rate / extent of hair growth in a patient by about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99%, about 100%.

[0174] In certain aspects, the present invention is not limited by the method of applying or administering the composition. The composition may be applied to the scalp, skin surface, or other target tissue, and the route of delivery does not materially affect the underlying biological mechanism of action. Without limitation thereto, the composition may be delivered by topical application, transdermal absorption, injection, or other dermal administration techniques.

[0175] In some aspects, when the composition is applied topically or transdermally, it may be advantageous to prepare the treatment area by cleansing, exfoliation, or adjustment of the local pH prior to application. The formulation may be massaged into the skin manually, delivered using devices such as syringes, pumps, rollers, or micro dispensing systems, or incorporated into a patch, gel, lotion, or transdermal delivery system. In certain aspects, the treated area may be covered to reduce evaporation and promote absorption. Regardless of the mode of administration, the efficacy of the treatment is primarily attributable to the composition itself rather than the delivery method.

[0176] Where the application area is essentially skin, it is helpful to seal-off the area of application after supplying a formulation and allowing the penetration to occur to restore the skin barrier. A convenient way to do this is to apply a composition comprising linoleic acid which effectively closes the entrance pathways that were provided by the penetrants of the disclosure. This application, too, is done by straightforward smearing onto the skin area or can be applied more precisely in measured amounts.

[0177] In some aspects, the methods include administering the composition in conjunction with microneedling. Microneedling, also known as collagen induction therapy, involves creating microscopic punctures in the skin to stimulate the body’s natural healing processes. Facial microneedling triggers collagen and elastin production, leading to improved skin texture and reduced fine lines. While this procedure is known to trigger collagen and elastin production for improving skin texture, the present disclosure utilizes it in a novel combination to enhance the delivery and efficacy of the PLLA composition for hair growth.

[0178] In some aspects the composition of PLLA can be administered to patients receivingAttorney Docket No. DRIP101WOtestosterone therapy or dihydrotestosterone (DHT) blockers and may be optimized for hormonally balanced or androgen-mediated hair loss populations. In certain aspects, the composition is used as part of a multimodal therapeutic regimen integrating biologies, pharmacologic agents, physical stimulation techniques, or controlled delivery devices to enhance overall hair growth outcomes.

[0179] In some aspects microneedling technique may be incorporated as described above. In some aspects, a glide medium is used to allow the microneedling device to move smoothly across the skin, minimizing friction, reducing discomfort, and ensuring consistent needle depth. The glide medium often contains hyaluronic acid.

[0180] The microneedling procedure may optionally be performed with or without an auxiliary bioactive agent contained in the glide medium. Non-limiting examples include microneedling with bioactives such as platelet-derived growth factors (PDGF), polynucleotides (PN), NAD boosters, exosomes, minoxidil, finasteride, or dutasteride. In some aspects, the composition is used together with a device engineered to deliver agents at a depth greater than that achieved by standard microneedling.

[0181] Microneedling creates micro-channels in the skin of a specific depth and width. PLA or derivative particles can penetrate micro-channels and reach the hair follicle bulge. This interaction is synergistic as the microneedling "primes" the follicle by creating a direct path for delivery, and the specific PLA or derivative particles composition provides a potent biostimulatory signal directly to the stem cell niche.

[0182] This synergy also arises from the PLA or derivative particles composition of the present disclosure, which is formulated with a low molecular weight and / or small particle size, which can penetrate and effectively reach the targeted hair follicle bulge region. This is a result that would not be achievable with conventional, larger PLLA particles used for dermal filling. The direct delivery of this PLLA composition to the follicular stem cell niche results in therapeutic activation.

[0183] In another aspect, the present invention provides a specialized delivery device, as depicted in the exemplary aspect of Figure 10a, engineered to provide uniform and repeatable delivery of a PLA or derivative particle suspension. The device is designed to solve the significant technical challenges associated with administering such suspensions, including particle sedimentation, aggregation, and clogging of fine microneedles, thereby enabling more consistent and predictable clinical outcomes.

[0184] As shown in Figure 10a, the device comprises a main housing with an ergonomic HAND grip for stable, single-handed operation. The device integrates several key systems: a multichamber reservoir system, an internal delivery mechanism, an energy application unit, and an electronic user interface.Attorney Docket No. DRIP101WO

[0185] The device includes a multi-chamber reservoir system, illustrated by CHAMBER 1 and CHAMBER 2. This dual-chamber design allows for versatile formulation handling. In one aspect, a first chamber holds a lyophilized powder of PL A particles or derivatives thereof, while a second chamber holds a sterile diluent or carrier. An internal mechanism may be activated to mix the components prior to administration, ensuring a fresh composition. In another aspect, the chambers can hold two different therapeutic compositions, allowing for sequential or simultaneous administration. The reservoirs are configured as replaceable, single-use cartridges to ensure sterility and accurate dosing. To address the problem of particle sedimentation, one or both chambers may include a micro-agitator, such as a small, low-power vibratory element or an oscillating paddle, which operates during use to continuously keep the PLA particles or derivatives thereof suspended uniformly within the carrier.

[0186] The methods of the present invention may be performed using an apparatus for administering the therapeutic composition to the scalp. As used herein, an "apparatus for administering" or a "PLLA dispensing means" refers to any device or system configured to deliver the PLLA particle suspension to the targeted dermal or subdermal layer of the scalp. This dispensing means can be broadly categorized into needle-based systems and needle-free systems.

[0187] Needle-Based Dispensing Means: In some aspects, the dispensing means comprises one or more needles for physically penetrating the epidermis. In one aspect, the apparatus is a standard medical syringe coupled with a needle or, preferably, a blunt-tip cannula. The cannula, for example a 25-gauge, 1.5-inch cannula, is used to create a channel in the deep dermis or subcutaneous plane, through which the PLLA composition is injected. In another aspect, the apparatus comprises a microneedle array, which includes a plurality of fine, hollow needles. The PLLA composition is dispensed from an integrated reservoir through these hollow needles directly into the dermis, as described previously.

[0188] In one aspect of the invention, the PLLA dispensing device utilizes a detachable and disposable treatment head as shown in Figure 10b. As illustrated at the distal end of the device in the figure, the treatment head is a self-contained unit that houses the components that come into direct contact with the subject's skin. This modular design is critical for ensuring sterility, preventing cross-contamination between patients, and maintaining the performance of the device.

[0189] The treatment head comprises a housing that mechanically and fluidically couples to the main body of the dispensing device. It incorporates a microneedle array at its distal end, which may include a single, central hollow needle or a plurality of hollow microneedles. These needles are fluidically connected to an internal manifold within the treatment head. When the head is attached to the device, this manifold forms a sterile fluidic connection with the delivery mechanismAttorney Docket No. DRIP101WOof the main device body, allowing the PLLA composition to be dispensed from the reservoir, through the treatment head, and out of the hollow needles.

[0190] In aspects that include an energy application unit, the treatment head is also configured to work in conjunction with this feature. For example, the housing of the treatment head may be partially transparent to sonic or light energy, allowing the energy generated by an emitter in the main device body (such as an ultrasound emitter) to pass through the head and be applied to the scalp tissue surrounding the needles. In another aspect, the treatment head itself may contain the energy-emitting components, which are electrically coupled to the main device body when attached.

[0191] The treatment head is designed to be single use. After the treatment session is complete, the entire head assembly can be detached from the main device body and safely discarded. A new, sterile treatment head can then be attached to the next patient. This ensures that the needles are always sharp and sterile, and that the internal fluidic pathways are free from any residual composition that could clog or contaminate the system, thereby guaranteeing the safety and efficacy of every treatment.

[0192] In other aspects, the dispensing means is a needle-free system that delivers the PLLA composition into the skin without requiring sharp, percutaneous needles. These systems utilize high-energy or high-pressure forces to propel the composition through the stratum comeum.

[0193] To overcome the high risk of clogging associated with simple positive pressure, the delivery mechanism is configured to generate a controlled, pulsatile flow. In one aspect, the mechanism comprises a micro-peristaltic pump or a piezoelectric pump that generates oscillating pressure pulses. This action prevents particle packing at the needle inlets and ensures a consistent, uniform flow rate through each hollow microneedle.

[0194] The device may further comprise an energy application unit integrated into the device head. As shown in Figure 10a, this unit can be a HALO ULTRASOUND EMITTER that surrounds the microneedle array. This configuration allows for the simultaneous application of sonic energy to the scalp tissue as the composition is being delivered. The application of this physical energy field is configured to facilitate enhanced distribution, permeation, and biostimulatory effect of the PLLA composition within the scalp. In other aspects, the energy field may be selected from electrical energy (e.g., radiofrequency) or thermal energy.

[0195] The device includes an electronic control system and user interface (UI), illustrated by the display screen and the ILLUMINATED UI RING. The screen may display key parameters such as remaining treatment time, dosage delivered, or battery life. The illuminated ring may provide visual feedback to the operator, indicating device status such as "ready," "delivering," or "error."Attorney Docket No. DRIP101WO

[0196] The device may be included as part of a kit, which may further comprise one or more cartridges pre-filled with the PLA composition or its components, disposable microneedle array tips, a charging station, and a set of instructions for use.

[0197] A micro-needling apparatus may be included in the kit and is configured for creating micro-channels in the skin of the scalp to the appropriate depth to enhance delivery and stimulate the follicular microenvironment. The apparatus is provided to be used in conjunction with the administration of the PLA or derivative particles composition to facilitate the synergistic method of the disclosure.

[0198] The kit further comprises a set of instructions for use. The instructions are a tangible component of the kit and may be provided as a printed paper insert, a label on the packaging, or via electronic means, such as a QR code or web address linking to a website with text, diagrams, or video instructions. Critically, the instructions will specify that steps are to be performed in a manner that achieves a uniform distribution of PLA or derivative particles resulting in a synergistic enhancement of hair follicle stem cell activation, an outcome not achievable by either step alone.

[0199] Alternatively, or in conjunction with the aspects described above, the devices provided herein may be used to deliver topical follicle-stimulating peptides, growth factors, vitamins, or other bioactive agents in combination with the compositions described herein. For example, the device may facilitate the infusion of an auxiliary therapeutic agent. Non-limiting examples of such agents include platelet-derived growth factors (PDGF), polynucleotides (PN), NAD boosters, exosomes, minoxidil, finasteride, or dutasteride.

[0200] In an alternative to administering via a syringe, the surface of the skin can be disrupted mechanically by the use of spring systems, laser powered systems, use of iontophoresis, systems propelled by Lorentz force or by gas or shock waves including ultrasound and may employ microdermabrasion such as by the use of sandpaper or its equivalent or using microneedles or electroporation devices. Simple solutions of the agent(s) as well as the above-listed transdermal delivery formulations that penetrate intact skin may be applied using occlusive patches, such as those in the form of micro-patches. External reservoirs of the formulations for extended administration may also be employed.

[0201] Accordingly, in certain aspects alternative methods of administering one or more therapeutic compounds or agents (e.g., medicaments) through intact skin are provided. As nonlimiting examples, these alternative methods might be selected from the following lists: on basis of working mechanism, spring systems, laser powered, energy-propelled, Lorentz force, gas / air propelled, shock wave (including ultrasound), on basis of type of load, liquid, powder, projectile, on basis of drug delivery mechanism, nano-patches, sandpaper (microdermabrasion),Attorney Docket No. DRIP101WOiontophoresis enabled, microneedles, on basis of site of delivery, intradermal, intramuscular, and subcutaneous injection.

[0202] Other suitable delivery mechanisms include, without limitation, microneedle drug delivery, such as 3M Systems, Glide SDI (pushes drug as opposed to “firing” drug), MIT low pressure injectors, micropatches (single use particle insertion device), microelectro mechanical systems (MEMS), dermoelectroporation devices (DEP), transdermal ionto system, TTS transdermal therapeutic systems, membrane-moderated systems (drug reservoir totally encapsulated in a shallow compartment), adhesive diffusion-controlled system (drug reservoir in a compartment fabricated from drug-impermeable metallic plastic backing), matrix dispersion type system (drug reservoir formed by homogeneously dispersing drug solids in a hydrophilic or lipophilic polymer matrix molder into medicated disc), and microreservoir system (combination of reservoir and matrix dispersion-type drug delivery system).

[0203] In some aspects, delivery may be achieved using devices suitable for home use, which may additionally incorporate follicle stimulation and / or red-light therapy to enhance hair growth. In other aspects, medical-grade devices intended for professional administration may be employed to deliver the composition under controlled conditions.

[0204] A formulation can be applied in a single, one-time application, once a week, once a biweek, once a month, or from one to twelve times daily, for a period of time sufficient to alleviate a condition, disease, disorder, symptoms, for example, for a period of time of one week, from 1 to 12 weeks or more, from 1 to 6 weeks, from 2 to 12 weeks, from 2 to 8 weeks, from 2 to 6 weeks, from 2 to 4 weeks, from 4 to 12 weeks, from 4 to 8 weeks, or from 4 to 6 weeks. The present compositions can be administered, for example, at a frequency of once per day to hourly if needed. The presently described formulations can be topically administered once or more per day for a period from 1 week to 4 weeks, or from 1 week to 2 weeks, for 1 week, for 2 weeks, for 3 weeks, or for 4 weeks or more. In some instances, it may also be desirable to continue treatment indefinitely, for example, to inhibit recurring inflammation. A suitable administration for a formulation comprising a skin cream, lotion or ointment, for example is once, twice, three, four times daily, or hourly if needed

[0205] As described above, if desired, other therapeutic agents can be employed in conjunction with those provided in the above-described compositions. The amount of active ingredients that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treatment, the nature of the disease, disorder, or condition, and the nature of the active ingredients.

[0206] It is understood that the specific dose of the composition administered to the scalp mayAttorney Docket No. DRIP101WOvary depending on factors such as the activity of the active agent(s) in the composition, the severity and pattern of hair loss, and the regions of the scalp being treated. One of ordinary skill in the art would recognize the influence of these factors and could determine suitable administration volumes or dosing regimens for individual patients using no more than routine experimentation.

[0207] Pharmacokinetic parameters such as bioavailability, absorption rate constant, apparent volume of distribution, unbound fraction, total clearance, fraction excreted unchanged, first-pass metabolism, elimination rate constant, half-life, and mean residence time can be determined by methods well known in the art.

[0208] A formulation in accordance with the subject matter described herein may be a topical dosage form packaged in, for example, a multi-use or single-use package, including for example, a tube, a bottle, a pump, a container or bottle, a vial, a jar, a packet, a blister package, or any other disposable or reusable container

[0209] Single dosage kits and packages containing a once-per-day amount of the formulation may be prepared. Single dose, unit dose, and once-daily disposable containers of the formulation are also provided.

[0210] Single coating application kits and packages containing a once per day amount of the coating may be prepared. Single dose, unit dose, and once-daily disposable containers of the coating are also provided.

[0211] It is understood that a specific dose level for any particular patient will vary depending upon a variety of factors, including the activity of the specific active agent; the age, body weight, general health, sex and diet of the patient; the time of administration; the rate of excretion; possible drug combinations; the severity of the particular condition being treated; the area to be treated and the form of administration. One of ordinary skill in the art would appreciate the variability of such factors and would be able to establish specific dose levels using no more than routine experimentation.

[0212] Pharmacokinetic parameters such as bioavailability, absorption rate constant, apparent volume of distribution, unbound fraction, total clearance, fraction excreted unchanged, first-pass metabolism, elimination rate constant, half-life, and mean residence time can be determined by methods well known in the art.

[0213] A formulation in accordance with the subject matter described herein may be a topical dosage form packaged in, for example, a multi-use or single-use package, including for example, a tube, a bottle, a pump, a container or bottle, a vial, a jar, a packet, or a blister package.

[0214] Dosing can be single dosage or cumulative (serial dosing), and can be readily determined by one skilled in the art. A formulation of the present disclosure may be administered once, twice,Attorney Docket No. DRIP101WOthree, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more times to a subject. For instance, treatment of a disease may comprise a one-time administration of an effective dose of a formulation as disclosed herein. Alternatively, treatment of a disease may comprise multiple administrations of an effective dose of a formulation as carried out over a range of time periods, such as, e.g., once daily, twice daily, thrice daily, once every few days, or once weekly. The timing of administration can vary from individual to individual, depending upon such factors as the severity of an individual's symptoms. For example, an effective dose of a formulation as disclosed herein can be administered to an individual once daily for an indefinite period, or until the individual no longer requires therapy. In one aspect, a formulation as disclosed herein is capable of decreasing the time to resolve the symptoms of a disease, including in an individual suffering from a disease by, e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95% as compared to a patient not receiving the same treatment.

[0215] The present formulation remains stable in storage for periods including up to about 5 years, between about 3 months and about 5 years, between about 3 months and about 4 years, between about 3 months and about 3 years, and alternately any time period between about 6 to about 12 months, 12 to about 18 months, 18 to about 24 months, 24 months to about 30 months, and 30 to about 3 years.

[0216] The formulation described herein remains stable for up to at least three years at a temperature of less than or equal to 40° C. In an aspect, the presently described formulation remains stable for at least two years at a temperature of less than or equal to 40° C. In an aspect, the presently described formulation remains stable for at least three years at a temperature of less than or equal to 40° C and at a humidity of up to 75% RH, for at least two years at a temperature of less than or equal to 40° C and at a humidity of up to 75% RH, or for at least three years at a temperature of less than or equal to 30°C. and at a humidity of up to 75% RH. In a further aspect, the presently described formulation remains stable for an extended period when packaged in a multi-use container such as a bottle dispenser or the like and exhibits equal to or even greater stability when packaged in a single-use package.

[0217] In a further aspect, a formulation and its derivatives have half-lives of 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, one month, two months, three months, four months or more.Attorney Docket No. DRIP101WO

[0218] In other aspects, the coating and its derivatives have half-lives of 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, one month, two months, three months, four months, five months, six months, one year, two years, three years, four years, five years or more.

[0219] In one aspect, the period of administration of a formulation is for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or more. In a further aspect, a period of during which administration is stopped is for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or more

[0220] The present disclosure may also feature kits for promoting hair growth or treating hair loss in a subject in need thereof. In some aspects, the kit comprises a composition as described herein. For example, the composition may comprise: PLA or a derivative thereof (e.g., PLLA, PDLA, or PDLLA) and a pharmaceutically acceptable carrier. In other aspects, the composition comprises PLLA and a pharmaceutically acceptable carrier.

[0221] In certain aspects, kits can comprise, without limitation, one or more creams or lotions comprising one or more formulations described herein.EXAMPLES

[0222] The following non-limiting examples illustrate methods of treating hair loss and promoting hair growth using compositions according to the present disclosure. It is to be understood that said examples are not intended to limit the present disclosure in any way. Equivalents or substitutes are within the scope of the present disclosure.Example 1

[0223] 1.1 PLLA administered in conjunction with Finasteride: Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat pattern hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair loss in women. It is usually taken orally but there are formulations for patients with hair loss, designed to minimize systemic exposure by acting specifically on hair follicles. Finasteride is a 5a-reductase inhibitor and therefore an antiandrogen. It works by decreasing the production of dihydrotestosterone (DHT) by about 70%. In addition to DHT, finasteride also inhibits the production of several anticonvulsantAttorney Docket No. DRIP101WOneurosteroids including allopregnanolone, androstanediol, and tetrahydrodeoxycorticosterone. In this example, PLLA injections as described above. After the initial treatment, the patient notes a gradual and significant improvement in the thickness of her hair. Treatments thereafter are continued every six months.

[0224] 1.2 PLLA administered with Microneedling and PDGF: A subject diagnosed with androgenetic alopecia receives a subcutaneous injection of a composition comprising PLLA along the affected scalp regions. Immediately following injection, the treated area undergoes microneedling at a depth of 1.5-2.0 mm, after which a PDGF-containing solution is applied topically. The combination of PLLA biostimulation and PDGF signaling is expected to enhance perifollicular vascularity and promote anagen initiation.

[0225] 1.3 PLLA administered with Microneedling and Polynucleotides (PN): A subject with diffuse hair thinning receives an injection of PLLA into the deep dermis at a standard dosing regimen. Following the injection, the treated scalp is subjected to microneedling, after which a polynucleotide (PN) formulation is applied topically. The combination of PLLA and PN is anticipated to enhance the extracellular matrix environment, increase fibroblast proliferation and activation, and synergistically support follicular regeneration.

[0226] 1.4 PLLA administered with Microneedling and NAD Boosters: A patient exhibiting progressive reductions in hair density receives PLLA injections across the frontal scalp. Immediately following injection, microneedling is performed, and a topical NAD-boosting solution is applied to the treated area. The patient returns six weeks later for a second identical treatment session. After approximately eight months, the patient reports increased hair thickness and overall improvement in scalp coverage. A subsequent treatment cycle is administered, and no adverse effects are observed

[0227] 1.5 PLLA administered with Microneedling and Exosomes: A subject with early-stage FPHL receives PLLA injections at 4-6-week intervals. After each of the first two injection sessions, microneedling is performed and a purified exosome preparation is applied topically to the treated regions. No further treatment is administered. Over the following year, the patient observes progressive improvement in hair density, thickness, and overall scalp coverage. No adverse effects are observed

[0228] 1.6 PLLA administered with Microneedling and Minoxidil: A patient with temple recession receives PLLA injection throughout the thinning regions. The scalp is then micro needled and a minoxidil solution is applied immediately afterward. Microneedling is expected to increase minoxidil penetration, while the PLLA injection provides a regenerative scaffold that supports more durable anagen induction.Attorney Docket No. DRIP101WO

[0229] 1.7 PLLA administered with Microneedling and Finasteride: A male subject with vertex thinning receives PLLA injections followed by microneedling and topical finasteride application. The combined therapy is expected to enhance transdermal delivery of finasteride — reducing local DHT levels while PLLA promotes remodeling of the extracellular matrix to support follicular recovery. The subject undergoes two treatment sessions spaced four weeks apart. Over the next six months, the patient observes progressive thickening of hair in the treated area. No adverse effects are observed

[0230] 1.8 PLLA administered with Microneedling and Dutasteride: A patient with rapidly progressing androgenetic alopecia receives PLLA injections, followed by microneedling and topical application of a dutasteride solution. This combined approach is expected to reduce perifollicular DHT activity while enhancing the collagen-stimulating effects of PLLA. The patient undergoes three treatment sessions spaced six weeks apart. Six months after the final session, the patient notes visible improvement in hair density, with no adverse effects observed.

[0231] 1.9 PLLA administered with Deep-Delivery Device: A subject receives PLLA injections followed by treatment with a device capable of delivering therapeutic agents deeper than conventional microneedling (e.g. jet-injection, micro-infusion, or hollow-microcone delivery). Application of an adjunct hair-growth serum is expected to reach deeper follicular structures and enhance synergy with PLLA-induced tissue remodeling. The subject undergoes two treatment sessions. Nine months after the final treatment, the patient reports noticeable improvement in hair density.

[0232] 1.10 PLLA administered in Patients Taking Testosterone / DHT Blockers: A subject already using systemic testosterone or DHT-blocking medications (e.g., finasteride, dutasteride, spironolactone) undergoes PLLA injection. The combination of hormonal modulation and localized biostimulation produces improved follicular density compared to hormonal therapy alone.

[0233] 1.11 PLLA administered with Topical Rapamycin: A subject presenting with age-related hair thinning receives subcutaneous injections of a composition comprising PLLA according to the methods described herein. Immediately following the injections, a topical formulation containing rapamycin, an mTOR pathway inhibitor, is applied to the treated areas of the scalp. This combination therapy is designed to amplify tissue remodeling and dermal papilla cell activation. The PLLA injection provides localized regenerative stimuli to enhance the extracellular matrix, while the topical rapamycin modulates intracellular pathways to delay cellular senescence, promote autophagy, and restore stem cell function, thereby maintaining a more metabolically efficient follicular microenvironment.Attorney Docket No. DRIP101WO

[0234] 1.12 PLLA administered with Red-light Therapy: A subject with FPHL undergoes a treatment protocol comprising injections of a PLLA composition into the thinning regions of the scalp. Each treatment session is immediately followed by the application of red-light therapy, delivered at wavelengths between 630 and 670 nm. This combination therapy is intended to enhance mitochondrial activity, modulate reactive oxygen species, and reduce local inflammation. The red-light therapy is expected to optimize cellular metabolism and enhance tissue responsiveness to the bioactive factors and biostimulatory effects of the PLLA injection, fostering a more robust scalp environment conducive to sustained hair growth.Example 2

[0235] The following is a non-limiting example of the present invention. It is to be understood that said example is not intended to limit the present invention in any way. Equivalents or substitutes are within the scope of the present invention.

[0236] For the purposes of consistency and replicability, treatments were previously administered to standardized scalp zones, specifically the frontal midline and bilateral temporal regions. These areas were selected based on their propensity to exhibit early thinning in female patients, a pattern consistently observed within our patient population. Each treatment zone measured approximately 2 cm x 2 cm and was demarcated with a micro-tattoo to standardize photography and subsequent treatment sessions. Previously, treatment was offered broadly to any patient seeking therapy for hair thinning. In future aspects, patient selection will be refined to include screening for factors that may influence hair growth outcomes, such as androgen activity, DHT modulation, and menopausal status, to optimize treatment efficacy across different physiologic conditions. Furthermore, treatment will be expanded to include additional areas of thinning, including the crown and posterior scalp, to comprehensively address varying patterns of hair loss.

[0237] Predefined areas of the scalp exhibiting hair loss are identified. In one aspect, three treatment zones are selected: the frontal midline and the bilateral temporal regions of thinning. To ensure precise localization for treatment and for photographic documentation in subsequent sessions, each treatment zone is demarcated, for example with a micro-tattoo of about 1 mm or less in diameter. An additional site, for example the posterior mid-scalp, may be similarly marked but left untreated to serve as an intra-patient control site for evaluating efficacy.

[0238] A group of subjects with clinically diagnosed female pattern hair loss were selected for treatment with a PLLA composition as described herein. Subjects may have experienced stable hair loss to exclude cases of transient or stress-induced shedding. Subjects underwent treatment targeting three predefined areas of the scalp: the frontal midline and bilateral temporal regions of thinning. Each treatment zone was demarcated with a micro-tattoo (<1 mm diameter) to standardizeAttorney Docket No. DRIP101WOphotographic documentation and precise localization for subsequent sessions. The posterior midscalp was similarly marked but left untreated to serve as an intra-patient control site.

[0239] Prior to each treatment session, local anesthesia was achieved by injecting about 0.5 to 2% lidocaine injected into each treatment zone. The composition comprising PLLA was then administered into the deep dermis. Within each treatment zone, the composition was distributed radially around the micro-tattoo. The composition was prepared immediately prior to injection by reconstituting the composition with 1 cc of 1% lidocaine and 9 cc of sterile water. During each session, this solution was injected into each temporal zone and 4 mL into the frontal midline zone.

[0240] In some aspects, subjects receiving the composition may also undergo microneedling immediately following PLLA injection in the same treated regions of the scalp. In certain examples, microneedling may be performed using platelet-derived growth factors (PDGF) or polynucleotides (PN) as a glide medium. Without wishing to limit the present disclosure to any theory or mechanism it is believed that the inclusion of PDGF or PN is intended to enhance the regenerative environment of the scalp by delivering bioactive molecules that support follicular health and promote hair growth.

[0241] Each subject received two treatment sessions, spaced 4-6 weeks apart. Subjects were instructed to massage the treated areas for 1 week following injection to promote even product distribution. Subjects were also advised to limit sun exposure and strenuous activity for 24 hours. Follow-up visits were conducted during four and six months to document treatment outcomes using standardized photography and clinical assessments.

[0242] Hair growth and quality were assessed using dermatoscopic imaging and associated analytical software. Non-limiting metrics include hair density, fiber diameter, follicular unit composition, terminal-to-vellus hair ratio, and interfollicular distance. Standardized photographs of the scalp may be captured from multiple angles (e.g., superior, lateral, crown, and parted views) under consistent lighting and positioning conditions. Subject-reported outcomes, such as satisfaction, perceived efficacy, and hair-related confidence, were also evaluated using structured questionnaires.

[0243] As used herein, the term “about” refers to plus or minus 10% of the referenced number.

[0244] Although there has been shown and described the preferred aspect of the present disclosure, it will be readily apparent to those skilled in the art that modifications may be made thereto which do not exceed the scope of the appended claims. Therefore, the scope of the disclosure is only to be limited by the following claims. In some aspects, the figures presented in this patent application are drawn to scale, including the angles, ratios of dimensions, etc. In some aspects, the figures are representative only and the claims are not limited by the dimensions of theAttorney Docket No. DRIP101WOfigures. In some aspects, descriptions of the disclosures described herein using the phrase “comprising” includes aspects that could be described as “consisting essentially of’ or “consisting of’, and as such the written description requirement for claiming one or more aspects of the present disclosure using the phrase “consisting essentially of’ or “consisting of’ is met.

[0245] Thus, the embodiments or aspects shown and described are merely exemplary and various alternatives, combinations, omissions, of specific components, or foreseeable alternative components, understood by one having ordinary skill in the art, described in the present disclosure or within the field of the present disclosure, are intended to fall within the scope of the appending claims. In this breadth, any combination of claims and claim dependencies, viable within the scope of this disclosure and in accordance with the technology of the disclosure, is explicitly contemplated within the scope of the appending claims.

[0246] Lastly, it will be appreciated that various aspects of the disclosure and / or aspects and other features and functions, or alternatives thereof, may be desirably combined into many other different systems or applications. Various presently unforeseen or unanticipated alternatives, modifications, variations, or improvements therein may be subsequently made by those skilled in the art which are also intended to be encompassed by the claims.

Claims

Attorney Docket No. DRIP101WOCLAIMSWhat is Claimed is:

1. A composition for treating hair loss and stimulating hair growth, the composition comprising polylactic acid (PLA) particles or derivatives thereof, in a pharmaceutically acceptable carrier; wherein the composition further comprises bacteriostatic or deionized water and at least one excipient; wherein the PLA particles or derivatives thereof are suspended in the carrier.

2. The composition of Claim 1, wherein the PLA or a derivative is selected from the group consisting of: poly-L-lactic acid (PLLA), poly-D-lactic acid (PDLA), and poly-D, L-lactic acid (PDLLA).

3. The composition of Claim 2, comprising PLLA particles.

4. The composition of Claim 3, wherein PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both.

5. The composition of Claim 3, wherein PLLA particles have an average molecular weight between 10 kDa and 30 kDa, or an average particle size of less than 10 pm, or both; and, wherein the PLA particles or derivatives thereof are suspended in the carrier at a concentration of about 0.1% to about 2% by weight.

6. The composition of Claim 3, wherein PLLA particles have an average molecular weight between 5 kDa and 30 kDa, or an average particle size of less than 5 pm, or both; and, wherein the poly-L-lactic acid particles are suspended in the carrier at a concentration of about 0.1% to about 2% by weight.

7. The composition of Claim 4, wherein PLLA particles are suspended in the carrier at a concentration of between .1% and 2% by weight, wherein at least one excipient is at a concentration between .5 and 3% by weight.

8. The composition of Claim 4, wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

9. The composition of Claim 4, wherein PLLA particles are suspended in the carrier at about 1.4 to 1.6 % by weight, wherein at least one excipient is at a concentration at about 2 to 2.3% by weight.

10. The composition of Claim 4, wherein PLLA particles are suspended in the carrier at a concentration of less than 1.3 to 1.6% by weight, and wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

11. The composition of Claim 5, wherein PLLA particles are suspended in the carrier at aAttorney Docket No. DRIP101WOconcentration of between .1 and 2% by weight, wherein at least one excipient is at a concentration between .5 and 3%.

12. The composition of Claim 5, wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

13. The composition of Claim 5, wherein PLLA particles are suspended in the carrier at about 1.3 to 1.6% by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3% by weight.

14. The composition of Claim 5, wherein PLLA particles are suspended in the carrier at a concentration of less than 1.3 to 1.6% by weight.

15. The composition of Claim 6, wherein PLLA particles are suspended in the carrier at a concentration of between .1 and 2% by weight, wherein at least one excipient is at a concentration between .5 and 3% by weight.

16. The composition of Claim 6, wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

17. The composition of Claim 6, wherein PLLA particles are suspended in the carrier at about 1.3 to 1.6% by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3% by weight.

18. The composition of Claim 6, wherein PLLA particles are suspended in the carrier at a concentration of less than 1.3 to 1.6% by weight.

19. The composition of any of Claims 3-18, wherein the composition is administered transdermally, intradermally, or via a subcutaneous injection.

20. The composition of any of Claims 3-19, wherein the composition is administered by subcutaneous injection at one or more sites of the scalp, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

21. The composition of any of Claims 3-20, wherein the composition is administered to tissue associated with hair follicles, and / or wherein the composition is administered at and / or near a hair follicle, or wherein the composition is administered at or near hair follicle bulge stem cells.

22. The composition of any of Claims 3-21, wherein the composition has a pH in a range of about 4.5 to about 8.5.

23. The composition of any of Claims 3-22, wherein the composition has a pH in a range of about 6.5 to about 7.5.Attorney Docket No. DRIP101WO24. The composition of any of Claims 3-23, wherein the composition is administered at a depth of about 1 to 3 mm, 3 to 5 mm, or 5 to 7 mm.

25. The composition of any of Claims 3-24, wherein the composition is administered at an angle of about 10 to 15°, 15 to 20°, or 20 to 25° relative to the skin surface.

26. The composition of any of Claims 3-25, wherein the composition is administered with a blunt-tip cannula.

27. The composition of any of Claims 3-26, further comprising composition administration with a step of microneedling.

28. The composition of any of Claims 3-27, wherein the composition further comprises one or more additives, wherein the one or more additives comprise minoxidil, finasteride, or dutasteride.

29. The composition of any of Claims 3-28, wherein the composition further comprises one or more bioactive agents, wherein the one or more bioactive agents include growth factors, polynucleotides, Nicotinamide Adenine Dinucleotide (NAD) boosters, or exosomes.

30. The composition of any of Claims 3-29, further comprising lidocaine.

31. The composition of any of Claims 3-30, wherein the lidocaine provides a pH in a range of about 5.0 to about 6.

532. A system for treating hair loss or stimulating hair growth on a scalp of a subject, the system comprising:(a) a therapeutic composition comprising poly-L-lactic acid (PLLA) particles, in a pharmaceutically acceptable carrier, and the therapeutic composition comprising bacteriostatic or deionized water and at least one excipient; and,(b) a set of instructions directing that the composition be administered to the scalp and that microneedling be performed on the scalp in a manner that provides enhancement of hair growth.

33. The system according to any of Claims 32, wherein the therapeutic composition further comprises lidocaine.

34. The system of Claim 32 or 33, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles in the therapeutic composition are suspended in the carrier at a concentration of between .1% and 2% by weight, and wherein at least one excipient is at a concentration between .5 and 3%.Attorney Docket No. DRIP101WO35. The system of Claim 32 or 33, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles in the therapeutic composition are suspended in the carrier at a concentration of between 14 and 16 mg / mL, and wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

36. The system of Claim 32 or 33, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles in the therapeutic composition are suspended in the carrier at about 1.3 to 1.6% by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3 % by weight.

37. The system of Claim 32 or 33, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles in the therapeutic composition are suspended in the carrier at a concentration of less than 1.3 to 1.6% by weight.

38. The system according to any of Claims 32-37, wherein the therapeutic composition is administered transdermally, intradermally, or via a subcutaneous injection.

39. The system according to any of Claims 32-38, wherein the therapeutic composition is administered by subcutaneous injection at one or more sites of the scalp, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

40. The system according to any of Claims 32-39, wherein the therapeutic composition is administered to tissue associated with hair follicles, and / or wherein the composition is administered at and / or near a hair follicle, or wherein the composition is administered at or near hair follicle bulge stem cells.

41. The system according to any of Claims 32-40, wherein the therapeutic composition has a pH in a range of about 4.5 to about 8.5.

42. The system according to any of Claims 32-41, wherein the therapeutic composition has a pH in a range of about 6.5 to about 7.5.

43. The system according to any of Claims 32-42, wherein the therapeutic composition is administered at a depth of about 1 to 3 mm, 3 to 5 mm, or 5 to 7 mm.

44. The system according to any of Claims 32-43, wherein the therapeutic composition is administered at an angle of about 10 to 15°, 15 to 20°, or 20 to 25° relative to the skin surface.

45. The system according to any of Claims 32-44, wherein the therapeutic composition is administered with a blunt-tip cannula.Attorney Docket No. DRIP101WO46. The system according to any of Claims 32-45, further comprising therapeutic composition administration with a step comprising microneedling.

47. The system according to any of Claims 32-46, wherein the therapeutic composition further comprises one or more additives, wherein the one or more additives comprise minoxidil, finasteride, or dutasteride.

48. The system according to any of Claims 32-47, wherein the therapeutic composition further comprises one or more bioactive agents, wherein the one or more bioactive agents include growth factors, polynucleotides, Nicotinamide Adenine Dinucleotide (NAD) boosters, or exosomes.

49. The system according to any of Claims 32-48, wherein the therapeutic composition has a pH in a range of about 6.5 to 7.5.

50. The system according to any of Claims 32-49, wherein the lidocaine provides a pH in a range of about 5 to about 6.

51. The system according to any of Claim 32-50, wherein the instructions direct the therapeutic composition to be administered at a subdermal depth specifically targeting the hair follicle bulge region, wherein the instructions are provided on a printed insert within a package containing the composition.

52. The system according to any of Claim 46-51, wherein the instructions direct the therapeutic composition to be administered at a subdermal depth specifically targeting the hair follicle bulge region, wherein the instructions are provided on a printed insert within a package containing the composition and a microneedling apparatus, and wherein the instructions direct administration of the therapeutic composition and microneedling to be performed in a uniform fashion across a treatment area to enhance hair follicle stem cell activation53. A composition comprising poly-L-lactic acid (PLLA) particles in a pharmaceutically acceptable carrier, for use in a method of treating hair loss or stimulating hair growth in a subject; and, comprising bacteriostatic or deionized water and at least one gelling agent; wherein the PLLA particles are suspended in the carrier.

54. The composition of PLLA particles of Claim 53, having an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, comprising bacteriostatic or deionized water and at least one excipient; wherein PLLA particles are suspended in the carrier at a concentration of between .1% and 3% by weight, wherein at least one excipient is at a concentration between .5 and 3% by weight.Attorney Docket No. DRIP101WO55. The composition of PLLA particles Claim 53, having an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, comprising bacteriostatic or deionized water and at least one excipient; wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL by weight, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

56. The composition of PLLA particles Claim 53, having an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, comprising bacteriostatic or deionized water and at least one excipient; wherein PLLA particles are suspended in the carrier at about 1.3 to 1.6% by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3% by weight.

57. The composition of PLLA particles Claim 53, having an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, comprising bacteriostatic or deionized water and at least one excipient, wherein PLLA particles are suspended in the carrier at a concentration of less than 1.3 to 1.6% by weight.

58. The composition of any of Claims 53-57, wherein the composition is administered transdermally, intradermally, or via a subcutaneous injection at one or more sites of the scalp, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

59. The composition of any of Claims 53-58, wherein the composition is administered to tissue associated with hair follicles, and / or wherein the composition is administered at and / or near a hair follicle, or wherein the composition is administered at or near hair follicle bulge stem cells.

60. The composition of any of Claims 53-59, wherein the composition has a pH in a range of about 4.5 to about 8.5.

61. The composition of any of Claims 53-60, wherein the composition has a pH in a range of about 6.5 to about 7.5.

62. The composition of any of Claims 53-61, wherein the composition is administered at a depth of about 1 to 3 mm, 3 to 5 mm, or 5 to 7 mm.

63. The composition of any of Claims 53-62, wherein the composition is administered at an angle of about 10 to 15°, 15 to 20°, or 20 to 25° relative to the skin surface.

64. The composition of any of Claims 53-63, wherein the composition is administered with a blunt-tip cannula.

65. The composition of any of Claims 53-64, further comprising composition administration with a step of microneedling.Attorney Docket No. DRIP101WO66. The composition of any of Claims 53-65, wherein the composition further comprises one or more additives, wherein the one or more additives comprise minoxidil, finasteride, or dutasteride.

67. The composition of any of Claims 53-66, wherein the composition further comprises one or more bioactive agents, wherein the one or more bioactive agents include growth factors, polynucleotides, Nicotinamide Adenine Dinucleotide (NAD) boosters, or exosomes.

68. The composition of any of Claims 53-67, further comprising lidocaine.

69. The composition of any of Claims 53-68, wherein the lidocaine provides a pH in a range of about 5.0 to about 6.5.

70. A method for promoting hair growth or treating hair loss in a subject in need thereof, the method comprising, administering to the subject a therapeutic composition comprising poly-L-lactic acid (PLLA) particles, in a pharmaceutically acceptable carrier; and, the therapeutic composition comprising bacteriostatic or deionized water and at least one excipient, wherein the PLLA particles are suspended in the carrier, wherein the PLLA particles function as a pro-drug by degrading in situ to provide a sustained release of lactic acid, thereby modulating cellular metabolism in follicular cells to stimulate hair growth.

71. The method of Claim 70, wherein the therapeutic composition of PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles are suspended in the carrier at a concentration of between .1% and 3% by weight, wherein at least one excipient is at a concentration between .5 and 3% by weight.

72. The method of Claim 70, wherein the therapeutic composition of PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL by weight, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

73. The method of Claim 70, wherein the composition of PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles are suspended in the carrier at about 1.3 to 1.6% by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3% by weight.

74. The method of Claim 70, wherein the composition of PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at a concentration of less than 1.3 to 1.6% by weight.Attorney Docket No. DRIP101WO75. The method of any of Claims 70-74, wherein the therapeutic composition is administered by subcutaneous injection at one or more sites of the scalp, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

76. The method of any of Claims 70-75, wherein the therapeutic composition is administered to tissue associated with hair follicles.

77. The method of any of Claims 70-76, wherein the therapeutic composition is administered to tissue associated with hair follicles, and / or wherein the composition is administered at and / or near a hair follicle, or wherein the composition is administered at or near hair follicle bulge stem cells.

78. The method of any of Claims 70-77, wherein the therapeutic composition has a pH in a range of about 4.5 to about 8.5.

79. The method of any of Claims 70-78, wherein the therapeutic composition has a pH in a range of about, 5.5 to about 6.5, 6.5 to about 7.5, or 7.5 to about 8.5.

80. The method of any of Claims 70-79, wherein the therapeutic composition is administered at an angle of about 10 to 15°, 15 to 20°, or 20 to 25° relative to the skin surface.

81. The method of any of Claims 70-80, wherein the therapeutic composition is administered with a blunt-tip cannula.

82. The method of any of Claims 70-81, comprising a step of microneedling.

83. The method of any of Claims 70-82, wherein the therapeutic composition further comprises one or more additives, wherein the one or more additives comprise minoxidil, finasteride, or dutasteride.

84. The method of any of Claims 70-83, wherein therapeutic composition further comprises one or more bioactive agents, wherein the one or more bioactive agents include growth factors, polynucleotides, Nicotinamide Adenine Dinucleotide (NAD) boosters, or exosomes.

85. The method of any of Claims 70-84, wherein the therapeutic composition further comprises lidocaine.

86. The method of any of Claims 70-85, wherein the lidocaine provides a pH in a range of about 5.0 to about 6.5.Attorney Docket No. DRIP101WO87. A device for stimulating hair growth on a scalp, the device comprising:(a) a housing with a hand grip;(b) a reservoir system contained within the housing, the reservoir system configured to hold a therapeutic composition comprising poly-L-lactic acid (PLLA) particles suspended in a pharmaceutically acceptable carrier;(c) a PLLA dispensing means at a distal end of the housing operably coupled to the reservoir, the dispensing means configured to deliver the PLLA particles from the reservoir into a dermal or subdermal layer of the scalp.

88. The device of Claim 87, wherein the reservoir system comprises at least two separate chambers.

89. The device of Claim 87 or 88, wherein the reservoir system includes a micro-agitator configured to maintain a uniform suspension of the PLLA particles.

90. The device of any one of Claims 87-89, wherein the delivery mechanism comprises a pump configured to generate a pulsatile flow to dispense the composition.

91. The device of any one of Claims 87-90, the housing is configured to removably couple to a main body of the handheld device.

92. The device of Claim 91, wherein the energy application unit is an ultrasound emitter configured as a halo, surrounding the PLLA dispensing means.

93. The device of any one of Claims 87-92, wherein the PLLA dispensing means comprises at least one needle for physically penetrating an epidermis of the scalp, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

94. The device of any one of Claims 87-93, wherein the PLLA dispensing means is a needle-free system.

95. The device according to any of Claims 87-94, wherein the therapeutic composition of PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, comprising bacteriostatic or deionized water and at least one excipient; wherein PLLA particles are suspended in the carrier at a concentration of between .1% and 3% by weight, wherein at least one excipient is at a concentration between .5 and 3% by weight.

96. The device according to Claim 95, wherein the therapeutic composition comprises PLLA particles having an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, comprising bacteriostatic or deionized water and at least one excipient; wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL by weight, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.Attorney Docket No. DRIP101WO97. The device according to Claim 95, wherein the therapeutic composition comprises PLLA particles having an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, comprising bacteriostatic or deionized water and at least one excipient; wherein PLLA particles are suspended in the carrier at about 1.3 to 1.6% by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3% by weight.

98. The device according to Claim 95, wherein the therapeutic composition comprises PLLA particles having an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, comprising bacteriostatic or deionized water and at least one excipient, wherein PLLA particles are suspended in the carrier at a concentration of less than 1.45% by weight.

99. A composition for stimulating hair growth, the composition comprising: (a) poly-L-lactic acid (PLLA) particles, in a pharmaceutically acceptable carrier; (b) one or more excipients; and, (c) bacteriostatic or deionized water; wherein the PLLA particles are suspended in the carrier, wherein the particles are formulated as a sustained-release depot for lactic acid.

100. The composition of Claim 99, wherein the composition is not for use as a dermal filler or for wrinkle reduction.

101. The composition of Claim 99 or 100, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles are suspended in the carrier at a concentration of between .1% and 2% by weight, wherein at least one excipient is at a concentration between .5 and 3% by weight.

102. The composition of Claim 99 or 100, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL by weight, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

103. The composition of Claim 99 or 100, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles are suspended in the carrier at about 1.3 to 1.6 % by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3% by weight.

104. The composition of Claim 99 or 100, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both; wherein PLLA particles are suspended in the carrier at a concentration of less than 1.3 to 1.6% by weight.

105. The composition of any of Claims 99-104, wherein the composition is administered transdermally, intradermally, or via a subcutaneous injection.Attorney Docket No. DRIP101WO106. The composition of any of Claims 99-105, wherein the composition is administered by subcutaneous injection at one or more sites of the scalp, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

107. The composition of any of Claims 99-106, wherein the composition is administered to tissue associated with hair follicles, and / or wherein the composition is administered at and / or near a hair follicle, or wherein the composition is administered at or near hair follicle bulge stem cells.

108. The composition of any of Claims 99-107, wherein the composition has a pH in a range of about 4.5 to about 8.5.

109. The composition of any of Claims 99-108, wherein the composition has a pH in a range of about 5.5 to about 6.5, 6.5 to about 7.5, 7.5 to about 8.5.

110. The composition of any of Claims 99-109, wherein the composition is administered at a depth of about 1 to 3 mm, 3 to 5 mm, or 5 to 7 mm.

111. The composition of any of Claims 99-110, wherein the composition is administered at an angle of about 10 to 15°, 15 to 20°, or 20 to 25° relative to the skin surface.

112. The composition of any of Claims 99-111, wherein the composition is administered with a blunt-tip cannula.

113. The composition of any of Claims 99-112, further comprising composition administration with a step of microneedling.

114. The composition of any of Claims 99-113, wherein the composition further comprises one or more additives, wherein the one or more additives comprise minoxidil, finasteride, or dutasteride.

115. The composition of any of Claims 99-114, wherein the composition further comprises one or more bioactive agents, wherein the one or more bioactive agents include growth factors, polynucleotides, Nicotinamide Adenine Dinucleotide (NAD) boosters, or exosomes.

116. The composition of any of Claims 99-115 further comprising lidocaine.

117. The composition of any of Claims 99-116, wherein the lidocaine provides a pH in a range of about 4 to about 5, 5.0 to about 6.5, or 6.5 to about 7.

118. A composition comprising poly-L-lactic acid (PLLA) particles for use in a method of stimulating hair growth on a scalp of a subject, wherein the PLLA particles are suspended in a pharmaceutically acceptable carrier, wherein the composition comprises bacteriostatic or deionized water and at least one excipient, wherein the PLLA particles function as a pro-drug that degrades in situ to provide a sustained release of lactic acid to follicular cells.Attorney Docket No. DRIP101WO119. The composition according to Claim 118, wherein the PLLA particles function as a sustained-release depot for lactic acid.

120. The composition according to Claim 118, wherein the PLLA particles function as a sustained-release depot for lactic acid.wherein the sustained-release depot releases lactic acid into the target tissue over a period of at least 30 days.

121. The composition according to Claim 118, wherein the PLLA particles function as a sustained-release depot for lactic acid.

122. The composition according to Claim 118, wherein the PLLA particles function as a sustained-release depot for lactic acid, wherein the PLLA particles form a bioresorbable matrix upon administration that provides the sustained release of lactic acid.

123. The composition according to Claim 118, wherein the sustained release of lactic acid provides a durable biostimulatory signal to follicular cells for a period of at least four weeks.

124. The composition of Claim 118, wherein the composition is not for use as a dermal filler or for wrinkle reduction.

125. The composition according to any of Claims 118 to 124, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at a concentration of between .1% and 2% by weight, wherein at least one excipient is at a concentration between .5 and 3%.

126. The composition according to any of Claims 118 to 124, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL by weight, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

127. The composition according to any of Claims 118 to 124, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at about 1.3 to 1.6% by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3% by weight.

128. The composition according to any of Claims 118 to 124, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at a concentration of less than 1.45% by weight.Attorney Docket No. DRIP101WO129. The composition of any of Claims 118-128, wherein the composition is administered by subcutaneous injection at one or more sites of the scalp, wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling.

130. The composition of any of Claims 118-129, wherein the composition is administered to tissue associated with hair follicles, and / or wherein the composition is administered at and / or near a hair follicle, or wherein the composition is administered at or near hair follicle bulge stem cells.

131. The composition of any of Claims 118-130, wherein the composition has a pH in a range of about 4.5 to about 8.5.

132. The composition of any of Claims 118-131, wherein the composition has a pH in a range of about 5.5 to about 6.5, 6.5 to about 7.5, 7.5 to about 8.5.

133. The composition of any of Claims 118-132, wherein the composition is administered at a depth of about 1 to 3 mm, 3 to 5 mm, or 5 to 7 mm.

134. The composition of any of Claims 118-133, wherein the composition is administered at an angle of about 10 to 15°, 15 to 20°, or 20 to 25° relative to the skin surface.

135. The composition of any of Claims 118-134, wherein the composition is administered with a blunt-tip cannula.

136. The composition of any of Claims 118-135, further comprising composition administration with a step of microneedling.

137. The composition of any of Claims 118-136, wherein the composition further comprises one or more additives, wherein the one or more additives comprise minoxidil, finasteride, or dutasteride.

138. The composition of any of Claims 118-137, wherein the composition further comprises one or more bioactive agents, wherein the one or more bioactive agents include growth factors, polynucleotides, Nicotinamide Adenine Dinucleotide (NAD) boosters, or exosomes.

139. The composition of any of Claims 118-138, further comprising lidocaine.

140. The composition of any of Claims 118-139, wherein the lidocaine provides a pH in a range of about 4 to about 5, 5.0 to about 6.5, 6.5 to about 7.5.Attorney Docket No. DRIP101WO141. A system for treating hair loss or stimulating hair growth on a scalp of a subject, the system comprising:(a) a therapeutic composition comprising poly-L-lactic acid (PLLA) particles, in a pharmaceutically acceptable carrier, and comprising bacteriostatic or deionized water and at least one excipient; wherein the PLLA particles are suspended in the carrier, wherein the therapeutic composition is formulated to function as a pro-drug for lactic acid wherein the composition is formulated for administration to the scalp to stimulate hair growth or treat hair loss, but not for dermal volume augmentation or wrinkle filling; and,(b) a set of instructions directing that the composition be administered to the scalp and that microneedling be performed on the scalp in a manner that provides enhancement of hair growth.

142. The system according to Claim 141, wherein the therapeutic composition comprising PLLA is formulated to function as a pro-drug that degrades in situ to provide a sustained release of lactic acid to follicular cells.

143. The system according to Claim 141, wherein the therapeutic composition comprising PLLA particles is formulated function as a sustained-release depot for lactic acid.

144. The system according to Claim 141, wherein the therapeutic composition comprising PLLA particles function as a sustained-release depot for lactic acid.

145. The system according to Claim 141, wherein the therapeutic composition comprising PLLA particles is formulated for sustained-release depot releases lactic acid into the target tissue over a period of at least 30 days.

146. The system according to Claim 141, wherein the therapeutic composition comprising PLLA particles form a bioresorbable matrix upon administration that provides the sustained release of lactic acid.

147. The system according to Claim 141, wherein the therapeutic composition comprising PLLA particles sustained release of lactic acid provides a durable biostimulatory signal to follicular cells for a period of at least four weeks.

148. The therapeutic composition of Claim 141, wherein the composition is not for use as a dermal filler or for wrinkle reduction.

149. The therapeutic composition according to any of Claims 141 to 148, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at a concentration of between .1% and 2% by weight, wherein at least one excipient is at a concentration between .5 and 3% by weight.Attorney Docket No. DRIP101WO150. The therapeutic composition according to any of Claims 141 to 149, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at a concentration of between 14 and 16 mg / mL by weight, wherein at least one excipient is at a concentration between 20 and 22 mg / mL.

151. The therapeutic composition according to any of Claims 141 to 150, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at about 1.3 to 1.6% by weight, wherein at least one excipient is at a concentration at about 1.9 to 2.3% by weight.

152. The therapeutic composition according to any of Claims 141 to 151, wherein the PLLA particles have an average molecular weight less than 70 kDa, or an average particle size of less than 20 pm, or both, wherein PLLA particles are suspended in the carrier at a concentration of less than 1.3 to 1.6% by weight.

153. The therapeutic composition of any of Claims 141-152, wherein the therapeutic composition is administered by subcutaneous injection at one or more sites of the scalp.

154. The therapeutic composition of any of Claims 141-153, wherein the therapeutic composition is administered to tissue associated with hair follicles, and / or wherein the composition is administered at and / or near a hair follicle, or wherein the composition is administered at or near hair follicle bulge stem cells.

155. The therapeutic composition of any of Claims 141-154, wherein the therapeutic composition has a pH in a range of about 4.5 to about 8.5.

156. The therapeutic composition of any of Claims 141-155, wherein therapeutic composition has a pH in a range of about 5.5 to about 6.5, 6.5 to about 7.5, or 7.5 to about 8.5.

157. The therapeutic composition of any of Claims 141-156, wherein the therapeutic composition is administered at a depth of about 1 to 3 mm, 3 to 5 mm, or 5 to 7 mm.

158. The therapeutic composition of any of Claims 141-157, wherein the therapeutic composition is administered at an angle of about 10 to 15°, 15 to 20°, or 20 to 25° relative to the skin surface.

159. The therapeutic composition of any of Claims 141-158, wherein the therapeutic composition is administered with a blunt-tip cannula.

160. The therapeutic composition of any Claims 141-159, further comprising composition administration with a step of microneedling.Attorney Docket No. DRIP101WO161. The therapeutic composition of any of Claims 141-160, wherein the therapeutic composition further comprises one or more additives, wherein the one or more additives comprise minoxidil, finasteride, or dutasteride.

162. The therapeutic composition of any of Claims 141-161, wherein the therapeutic composition further comprises one or more bioactive agents, wherein the one or more bioactive agents include growth factors, polynucleotides, Nicotinamide Adenine Dinucleotide (NAD) boosters, or exosomes.

163. The therapeutic composition of any of Claims 141-162, further comprising lidocaine.

164. The therapeutic composition of any of Claims 141-163, wherein the lidocaine provides a pH in a range of about 5.0 to about 6.5.

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