Compositions and methods for the treatment of androgenetic alopecia

Abstract

Methods and compositions for stimulating hair growth are disclosed. The compositions for stimulating hair growth include hyaluronic acid. Methods and compositions for treating androgenetic alopecia (AGA) are also provided herein. The methods for stimulating hair growth and / or for treating AGA include the step of administering such compositions to the skin of a patient.

Description

[Technical Field]

[0001] Reference to related applications This application claims the benefits of U.S. Provisional Application No. 63 / 457,928, filed on April 7, 2023, which is incorporated by reference. [Background technology]

[0002] Hair loss often has negative social and psychological impacts on the individual suffering from it. Many factors, including genetics, hormones, environmental exposure, medication, psychological stress, and nutrition, are thought to contribute to hair loss. One known treatment is hair transplantation, which requires anesthesia, is expensive, time-consuming, and sometimes painful. Other approaches include massage and acupuncture, but these have not been shown to be effective. Hormones and other drugs have been used to treat hair loss, but these treatments often cause undesirable side effects (e.g., hair growth in undesirable areas).

[0003] Therefore, an effective treatment to stimulate hair growth is needed. [Overview of the project]

[0004] This specification provides a method for treating androgenetic alopecia (AGA) in patients in need. In some embodiments, the method may include administering the composition described herein to the skin of the patient. In some embodiments, the method may include administering the composition of this disclosure to the skin of the patient via intradermal injection. In some embodiments, the composition may contain up to about 1% by weight of hyaluronic acid. For example, the composition may contain about 0.2% to about 0.4% by weight of hyaluronic acid. In some embodiments, the composition may be administered to the subject at least twice a week. In some embodiments, the composition may be administered about three times a week. In some embodiments, the composition may contain uncrosslinked hyaluronic acid. In some embodiments, the average molecular weight of the hyaluronic acid may be up to about 100 kDa.

[0005] In some embodiments, a method for treating AGA may include administering a composition to a patient on consecutive days of the week. In some embodiments, the composition may be administered for three consecutive days of the week. In some embodiments, the composition may be injected into the skin to a depth of about 0.1 mm or more. In some embodiments, the composition may be injected into the skin to a depth of about 0.6 mm to about 0.8 mm. In some embodiments, the injection area may be about 4 cm 2 The above may be the case. In some embodiments, the composition may be administered to or proximal to the stem cell region of the hair follicle in the target scalp.

[0006] In some embodiments, the composition may be administered to one or more areas of skin from the frontotemporal region and the parietal region of the patient's scalp.

[0007] In some embodiments, treatment with the composition can improve or increase the number of hairs in the target area (TAHC), the width of hairs in the target area (TAHW), and / or the blackness of the hair.

[0008] In some embodiments, the composition is administered to patients who have experienced hair loss for approximately 3 to 5 years prior to administration of the composition. In some embodiments, the composition is administered to patients who have experienced hair loss for approximately 10 years prior to administration of the composition. In some embodiments, the patient has previously undergone a hair transplant. In some embodiments, the patient has undergone a hair transplant approximately 1 to 2 months prior to administration of the composition. In some embodiments, the patient is a male patient.

[0009] In some embodiments, the compositions of the present disclosure may be used to treat mild or moderate androgenetic alopecia (AGA). In some embodiments, the compositions of the present disclosure may be used to treat patients with a modified Norwood-Hamilton scale score of III or IV. In some embodiments, improvement or increase in TAHC, TAHW, and / or hair blackness is measured about 10 to 160 days after administration of the composition.

[0010] In some embodiments, the patient has previously experienced hair loss.

[0011] In some embodiments, the compositions of the present disclosure can stimulate hair growth in the frontotemporal region of the patient's scalp and / or the parietal region of the patient's scalp.

[0012] Methods for stimulating hair growth in a patient's skin are also provided herein. These methods may include administering the compositions of the disclosure to the patient's skin. In some embodiments, the compositions may be administered to the patient via intradermal injection. In some embodiments, the compositions of the disclosure may contain up to 1% by weight of hyaluronic acid, for example, about 0.2% to about 0.4% by weight of hyaluronic acid. In some embodiments, the compositions of the disclosure may be administered at least twice a week. For example, the compositions may be administered about three times a week. In some embodiments, the compositions may contain uncrosslinked hyaluronic acid. In some embodiments, the average molecular weight of the hyaluronic acid may be up to about 100 kDa.

[0013] This disclosure provides a method for administering a hair growth composition to a patient in need thereof. The method may include administering the composition of this disclosure to the patient's skin. In some embodiments, the composition may be administered by intradermal injection. In some embodiments, the composition may contain up to about 1% by weight of hyaluronic acid (e.g., about 0.2% to about 0.4% by weight of hyaluronic acid). The composition may be administered at least twice a week, for example, about three times a week. In some embodiments, the composition may contain uncrosslinked hyaluronic acid. In some embodiments, the average molecular weight of the hyaluronic acid may be up to about 100 kDa.

[0014] In some embodiments, the method for hair growth may include administering the composition to the patient on consecutive days. In one embodiment, the composition may be administered for three consecutive days per week. In some embodiments, the composition may be injected into the skin to a depth of about 0.1 mm or more, for example, about 0.6 mm to about 0.8 mm. In some embodiments, the injection area may be about 4 cm 2 The above may be true. In some embodiments, the compositions of the present disclosure may be administered to or proximal to the stem cell region of a hair follicle.

[0015] In some embodiments, the hair growth composition may be administered to one or more areas of skin from the frontotemporal region of the patient's scalp and the parietal region of the patient's scalp.

[0016] In some embodiments, treatment with the composition can improve or increase the number of hairs in the target area (TAHC), the width of hairs in the target area (TAHW), and / or the blackness of the hair.

[0017] In some embodiments, the composition is administered to patients who have experienced hair loss for approximately 3 to 5 years prior to administration of the composition. In some embodiments, the composition is administered to patients who have experienced hair loss for approximately 10 years prior to administration of the composition. In some embodiments, the patient has previously undergone a hair transplant. In some embodiments, the patient has undergone a hair transplant approximately 1 to 2 months prior to administration of the composition. In some embodiments, the patient is a male patient.

[0018] In some embodiments, the composition may be used for hair regrowth in patients with AGA. AGA may be mild or moderate. In some embodiments, the composition of the present disclosure may be used to treat hair loss in patients with a modified Norwood Hamilton scale score of III or IV. In some embodiments, improvement or increase in TAHC, TAHW, and / or hair blackness is measured about 10 to about 160 days after administration of the composition. [Brief explanation of the drawing]

[0019] The following detailed description of embodiments of compositions and methods for stimulating hair growth will be better understood when read in conjunction with the accompanying drawings. However, it should be understood that the present invention is not limited to the exact arrangement shown.

[0020] The drawing is as follows:

[0021] [Figure 1] This figure shows the characteristics associated with each modified Norwood Hamilton scale score. [Modes for carrying out the invention]

[0022] I. Composition In some embodiments, the hair growth stimulating composition includes hyaluronic acid. In some embodiments, compositions described in U.S. Patent No. 11,337,993 may be used in this disclosure (the contents thereof are incorporated herein by reference in their entirety).

[0023] 1. Hyaluronic acid (HA) HA is an endogenous, naturally occurring glycosaminoglycan. HA is found in the extracellular matrix and is widely distributed throughout the body, most abundantly present in the skin (approximately 50%). HA is primarily produced by mesenchymal cells, and its functions in the body include water retention; involvement in skin hydration and viscoelasticity; promotion of ionic solute and nutrient transport; and protection of the skin from free radical damage (Erickson & Stern, 2012).

[0024] In some embodiments, compositions useful for stimulating hair growth include hyaluronic acid. Hyaluronic acid is a natural ligand for CD44, is pro-inflammatory, and is currently known to stimulate hair growth. Hyaluronic acid is a natural linear polymer containing repeating disaccharide units of β-1,4-D-glucuronic acid and β-1,3-N-acetyl-D-glucosamine, as shown in formula (I) below.

[0025] [ka]

[0026] These units link together to form long, linear molecules, which, as they lengthen, form random coils. At concentrations higher than 0.1%, the HA chains form a continuous network. HA can be chemically reinforced to form crosslinks between HA molecules for the purpose of modifying the physical properties of the product.

[0027] HA has been studied in a variety of medical applications, including aesthetic (i.e., dermal fillers), ophthalmic (viscoelastic), and osteoarthritis applications. Several commercially available HA products are available in the United States, including dermal fillers such as Juvederm and Restylane; viscoelastic products such as Healon and NuVisc; and osteoarthritis products such as Hyalgan and Orthovisc. HA-based mesotherapy (small intradermal injections) is well documented in the literature as a safe treatment for skin rejuvenation. Reported adverse events associated with HA have been mild and transient and have included injection site pain, itching, stinging, erythema, edema, petechiae, purpura, bruising, swelling, hematoma, dark circles under the eyes, petechiae, skin scratching, and pinpoint bleeding, allergic reactions, urticaria, and papulogenesis. The risks associated with HA dermal fillers are generally mild and transient, but in rare cases, serious complications have occurred due to vascular occlusion, including infection, embolism, and tissue necrosis. These events are associated with deep injection of cross-linked HA products. The present invention provides a non-cross-linked form of hyaluronic acid in phosphate-buffered saline (PBS) for use in the method described herein.

[0028] In some embodiments, hyaluronic acid has a low average molecular weight. In some embodiments, "low average molecular weight" as used herein refers to a range of about 15,000 Da to about 40,000 Da. In some embodiments, hyaluronic acid has an intermediate average molecular weight. In some embodiments, "intermediate average molecular weight" as used herein refers to a range of about 75,000 Da to about 350,000 Da. In some embodiments, hyaluronic acid has a high average molecular weight. In some embodiments, "high average molecular weight" as used herein refers to about 950,000 Da or more.

[0029] In some embodiments, hyaluronic acid has an average molecular weight in the range of about 4,000 Da or less to about 10,000 Da. In some embodiments, hyaluronic acid has an average molecular weight in the range of about 10,000 Da to about 100,000 Da. In some embodiments, hyaluronic acid has an average molecular weight in the range of about 100,000 Da to about 1,500,000 Da or more. In some embodiments, hyaluronic acid has an average molecular weight that can be about 40 kDa to about 100 kDa. In one embodiment, hyaluronic acid has an average molecular weight of about 60 kDa.

[0030] In some embodiments, hyaluronic acid is present in a range of approximately 1 kDa to 10 kDa, 10 kDa to 50 kDa, 50 kDa to 100 kDa, 100 kDa to 150 kDa, 200 kDa to 250 kDa, 300 kDa to 350 kDa, 400 kDa to 450 kDa, and 500 kDa. Approximately 550kDa, approximately 600kDa to approximately 650kDa, approximately 700kDa to approximately 750kDa, approximately 800kDa to approximately 850kDa, approximately 900kDa to approximately 1000kDa, approximately 1000kDa to approximately 1100kDa, approximately 1100kDa to approximately 1200kDa, approximately 1200kDa to approximately 1300kDa, approximately 1300kDa a ~ approx. 1400kDa, approx. 1400kDa ~ approx. 1500kDa, approx. 1kDa ~ approx. 100kDa, approx. 100kDa ~ approx. 250kDa, approx. 250kDa ~ approx. It has an average molecular weight of approximately ~1500kDa, approximately 1kDa to approximately 250kDa, approximately 1kDa to approximately 500kDa, approximately 100kDa to approximately 500kDa, approximately 250kDa to approximately 750kDa, approximately 500kDa to approximately 1000kDa, approximately 750kDa to approximately 1250kDa, or approximately 1000kDa to approximately 1500kDa.

[0031] In some embodiments, the average molecular weight of hyaluronic acid can be up to approximately 100 kDa. For example, the average molecular weight of hyaluronic acid can range from approximately 1 kDa to approximately 10 kDa, approximately 5 kDa to approximately 15 kDa, approximately 10 kDa to approximately 20 kDa, approximately 15 kDa to approximately 25 kDa, approximately 20 kDa to approximately 30 kDa, approximately 25 kDa to approximately 35 kDa, approximately 30 kDa to approximately 40 kDa, approximately 35 kDa to approximately 45 kDa, approximately 40 kDa to approximately 50 kDa, and approximately 45 kDa. ~55kDa, 50kDa~60kDa, 55kDa~65kDa, 60kDa~70kDa, 65kDa~75kDa, 70kDa~80kDa, 75kDa~85kDa, 80kDa~90kDa, 85kDa~95kDa, 90kDa~100kDa, 95kDa~105kDa a, about 100kDa - about 200kDa, about 150kDa - about 250kDa, about 200kDa - about 300kDa, about 250kDa - about 350kDa, about 300kDa - About 400kDa, about 350kDa to about 450kDa, about 400kDa to about 500kDa, about 450kDa to about 550kDa, about 500kDa to about 600kDa, about 5 It can range from 50kDa to approximately 650kDa, approximately 600kDa to approximately 700kDa, approximately 650kDa to approximately 750kDa, approximately 700kDa to approximately 800kDa, approximately 750kDa to approximately 850kDa, approximately 800kDa to approximately 900kDa, approximately 850kDa to approximately 950kDa, approximately 900kDa to approximately 1000kDa, and approximately 950kDa to approximately 1000kDa.

[0032] In some embodiments, the hyaluronic acid is not crosslinked. In some embodiments, the hyaluronic acid is substantially free of crosslinking. In some embodiments, the composition contains free hyaluronic acid, i.e., uncrosslinked hyaluronic acid. Generally, free hyaluronic acid is not exposed to crosslinking conditions. In some embodiments, the composition may contain free hyaluronic acid, which may be present at a concentration of 5 to 95 percent by weight of the total hyaluronic acid.

[0033] In some embodiments, hyaluronic acid is crosslinked. Crosslinking can improve the longevity of hyaluronic acid, and in some embodiments, a certain degree of crosslinking may be desirable. In some embodiments, hyaluronic acid has sufficient crosslinking to last for about one week. However, without being bound by the mechanism of action, hyaluronic acid is thought to be effective in stimulating hair growth by interacting with the CD44 receptor. Thus, in some embodiments, it is desirable that the hyaluronic acid not be crosslinked so extensively that the crosslinking interferes with the ability of the hyaluronic acid to interact with the CD44 receptor.

[0034] The hydroxyl (--OH), carboxyl (--COOH), and / or amide (--NHCOCH.sub.3) functional groups of hyaluronic acid can be crosslinked via ether bonds (R--O--R), ester bonds (R-COO--R), or carbodiimide, respectively. In some embodiments, hyaluronic acid is crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), glutaraldehyde (GTA), poly(ethylene glycol) diglycidyl ether (PEGDE), ethylene glycol diglycidyl ether (EGDE), divinyl sulfonate (DVS), or pentaerythritol tetraacrylate (PT).

[0035] Hyaluronic acid is about 1x10 -7 mol / cm 3 or more, about 2x10 -7 mol / cm 3 or more, about 3x10 -7 mol / cm 3 or more, about 4x10 -7 mol / cm 3 or more, about 5x10 -7 mol / cm 3 or more, about 6x10 -7 mol / cm 3 or more, about 7x10 -7 mol / cm 3 or more, about 8x10 -7 mol / cm 3Or larger, approximately 9x10 -7 mol / cm 3 Or more, approximately 1x10 -6 mol / cm 3 Or more, approximately 2x10 -6 mol / cm 3 Or more, approximately 3x10 -6 mol / cm 3 Or more, approximately 4x10 -6 mol / cm 3 Or more, approximately 5x10 -6 mol / cm 3 Or more, approximately 6x10 -6 mol / cm 3 Or more, approximately 7x10 -6 mol / cm 3 Or larger, approximately 8x10 -6 mol / cm 3 Or larger, approximately 9x10 -6 mol / cm 3 Or more, or about 1x10 -5 mol / cm 3 It may have a crosslinking density of about 1 × 10⁻⁶. In some embodiments, hyaluronic acid has a crosslinking density of about 1 × 10⁻⁶. -7 mol / cm 3 and approximately 1x10 -5 mol / cm 3 During that time, approximately 1x10 -7 mol / cm 3 and approximately 1x10 -6 mol / cm 3 Approximately 1x10 -7 mol / cm 3 and approximately 5x10 -7 mol / cm 3 During that time, approximately 5x10 -7 mol / cm 3 and approximately 1x10 -6 mol / cm 3 During that time, approximately 1 x 10 -7 mol / cm 3 and approximately 2x10 -7 mol / cm 3 During that time, approximately 2x10 -7 mol / cm 3 and 4x10 -7 mol / cm 3 During that time, approximately 4x10-7 mol / cm 3 and about 6x10 -7 mol / cm 3 and between about 6x10 -7 mol / cm 3 and about 8x10 -7 mol / cm 3 and between about 8x10 -7 mol / cm 3 and about 1x10 -6 mol / cm 3 and between about 1x10 -6 mol / cm 3 and about 1x10 -5 mol / cm 3 and between about 1x10 -6 mol / cm 3 and about 5x10 -6 mol / cm 3 and between about 5x10 -6 mol / cm 3 and about 1x10 -5 mol / cm 3 and between about 1x10 -6 mol / cm 3 and about 2x10 -6 mol / cm 3 and between about 2x10 -7 mol / cm 3 and about 4x10 -7 mol / cm 3 and between about 4x10 -7 mol / cm 3 and about 6x10 -7 mol / cm 3 and between about 6x10 -7 mol / cm 3 and about 8x10 -7 mol / cm 3 and between about 8x10 -7 mol / cm 3 and about 1x10 -5 mol / cm 3 and between or about 5x10 -7 [[ID=​​​​​​​​​The compositions of the present invention may contain an amount of hyaluronic acid sufficient to provide a therapeutic effect, for example, to stimulate hair growth in a patient who needs it, and / or to treat androgenic alopecia (AGA). In some embodiments, high concentrations of hyaluronic acid may cause undesirable inflammation. In some embodiments, the compositions of the present invention contain an amount of hyaluronic acid sufficient to provide a therapeutic effect, for example, sufficient to produce a therapeutic effect such as stimulating hair growth or treating AGA, and without causing an unacceptable or undesirable inflammatory response.

[0037] In some embodiments, the composition contains about 0.001% by weight or more of hyaluronic acid, about 0.0025% by weight or more of hyaluronic acid, about 0.0050% by weight or more of hyaluronic acid, about 0.0075% by weight or more of hyaluronic acid, about 0.01% by weight or more of hyaluronic acid, about 0.025% by weight or more of hyaluronic acid, about 0.05% by weight or more of hyaluronic acid, about 0.075% by weight or more of hyaluronic acid, about 0.1% by weight or more of hyaluronic acid, about 0.25% by weight or more of hyaluronic acid, about 0.5% by weight or more of hyaluronic acid, about 0.75% by weight or more of hyaluronic acid, or about 1% by weight or more of hyaluronic acid. In some embodiments, the composition contains about 0.001% to about 0.0025% by weight of hyaluronic acid, about 0.0025% to about 0.005% by weight of hyaluronic acid, about 0.0025% to about 0.0075% by weight of hyaluronic acid, about 0.0025% to about 0.01% by weight of hyaluronic acid, about 0.001% to about 0.01% by weight of hyaluronic acid, and about 0.005% to about 0.0075% by weight of hyaluronic acid. Acid, approximately 0.005% to approximately 0.01% by weight of hyaluronic acid, approximately 0.0075% to approximately 0.01% by weight of hyaluronic acid, approximately 0.01% to approximately 0.02% by weight of hyaluronic acid, approximately 0.01% to approximately 0.05% by weight of hyaluronic acid, approximately 0.02% to approximately 0.04% by weight of hyaluronic acid, approximately 0.05% to approximately 0.1% by weight of hyaluronic acid, approximately 0.04% to approximately 0.06% by weight of hyaluronic acid, approximately 0.06 Hyaluronic acid in amounts ranging from approximately 0.08% by weight to approximately 0.1% by weight, approximately 0.1% by weight to approximately 0.2% by weight, approximately 0.2% by weight to approximately 0.3% by weight, approximately 0.1% by weight to approximately 0.5% by weight, approximately 0.2% by weight to approximately 0.4% by weight, approximately 0.5% by weight to approximately 1% by weight, approximately 0.3% by weight to approximately 0.4% by weight, approximately 0. Contains 4% to approximately 0.5% by weight of hyaluronic acid, approximately 0.5% to approximately 0.6% by weight of hyaluronic acid, approximately 0.4% to approximately 0.6% by weight of hyaluronic acid, approximately 0.6% to approximately 0.7% by weight of hyaluronic acid, approximately 0.7% to approximately 0.8% by weight of hyaluronic acid, approximately 0.6% to approximately 0.8% by weight of hyaluronic acid, approximately 0.8% to approximately 0.9% by weight of hyaluronic acid, or approximately 0.8% to approximately 1% by weight of hyaluronic acid.In some embodiments, the composition is approximately 0.1% by weight, approximately 0.11% by weight, approximately 0.12% by weight, approximately 0.13% by weight, approximately 0.14% by weight, approximately 0.15% by weight, approximately 0.16% by weight, approximately 0.17% by weight, approximately 0.18% by weight, approximately 0.19% by weight, approximately 0.2% by weight, approximately 0.21% by weight, approximately 0.22% by weight, approximately 0.23% by weight, approximately 0.24% by weight, approximately 0.25% by weight, approximately 0.26% by weight, approximately 0.27% by weight, approximately 0.28% by weight, approximately 0.29% by weight, approximately 0.3% by weight, and approximately 0.31% by weight. %, about 0.32 weight%, about 0.33 weight%, about 0.34 weight%, about 0.35 weight%, about 0.36 weight%, about 0.37 weight%, about 0.38 weight%, about 0.39 weight%, about 0.4 weight%, about 0.41 weight%, about 0.42 weight%, about 0.43 Weight%, about 0.44% by weight, about 0.45% by weight, about 0.46% by weight, about 0.47% by weight, about 0.48% by weight, about 0.49% by weight, about 0.5% by weight, about 0.51% by weight, about 0.52% by weight, about 0.53% by weight, about 0.54% by weight, about 0. 55% by weight, approximately 0.56% by weight, approximately 0.57% by weight, approximately 0.58% by weight, approximately 0.59% by weight, approximately 0.6% by weight, approximately 0.61% by weight, approximately 0.62% by weight, approximately 0.63% by weight, approximately 0.64% by weight, approximately 0.65% by weight, approximately 0.66% by weight, approximately 0.67% by weight, approximately 0.68% by weight, approximately 0.69% by weight, approximately 0.7% by weight, approximately 0.71% by weight, approximately 0.72% by weight, approximately 0.73% by weight, approximately 0.74% by weight, approximately 0.75% by weight, approximately 0.76% by weight, approximately 0.77% by weight, approximately 0.78% by weight Contains approximately 0.79% by weight, approximately 0.8% by weight, approximately 0.81% by weight, approximately 0.82% by weight, approximately 0.83% by weight, approximately 0.84% ​​by weight, approximately 0.85% by weight, approximately 0.86% by weight, approximately 0.87% by weight, approximately 0.88% by weight, approximately 0.89% by weight, approximately 0.9% by weight, approximately 0.91% by weight, approximately 0.92% by weight, approximately 0.93% by weight, approximately 0.94% by weight, approximately 0.95% by weight, approximately 0.96% by weight, approximately 0.97% by weight, approximately 0.98% by weight, approximately 0.99% by weight, approximately 1% by weight or more of hyaluronic acid.

[0038] As used herein, both mcg / mL and ug / mL refer to micrograms per milliliter. In some embodiments, hyaluronic acid is present in compositions of about 10 mcg / mL or more, about 15 mcg / mL or more, about 20 mcg / mL or more, about 25 mcg / mL or more, about 30 mcg / mL or more, about 35 mcg / mL or more, about 40 mcg / mL or more, about 45 mcg / mL or more, about 50 mcg / mL or more, about 55 mcg / mL or more, about 60 mcg / mL or more, about 65 mcg / mL or more, about 70 mcg / mL or more, and about 75 mcg Compositions of 1 / mL or more, approximately 80mcg / mL or more, approximately 85mcg / mL or more, approximately 90mcg / mL or more, approximately 95mcg / mL or more, approximately 100mcg / mL or more, approximately 110mcg / mL or more, approximately 120mcg / mL or more, approximately 130mcg / mL or more, approximately 140mcg / mL or more, approximately 150mcg / mL or more, approximately 160mcg / mL or more, approximately 170mcg / mL or more, approximately 180mcg / mL or more, approximately 190mcg Compositions of approximately 200 mcg / mL or more, approximately 210 mcg / mL or more, approximately 220 mcg / mL or more, approximately 230 mcg / mL or more, approximately 240 mcg / mL or more, approximately 250 mcg / mL or more, approximately 260 mcg / mL or more, approximately 270 mcg / mL or more, approximately 280 mcg / mL or more, approximately 290 mcg / mL or more, approximately 300 mcg / mL or more, approximately 310 mcg / mL or more, approximately 320 mcg / mL or more, approximately 33 Compositions with 0 mcg / mL or more, compositions with approximately 340 mcg / mL or more, compositions with approximately 350 mcg / mL or more, compositions with approximately 360 mcg / mL or more, compositions with approximately 370 mcg / mL or more, compositions with approximately 380 mcg / mL or more, compositions with approximately 390 mcg / mL or more, compositions with approximately 400 mcg / mL or more, compositions with approximately 410 mcg / mL or more, compositions with approximately 420 mcg / mL or more, compositions with approximately 430 mcg / mL or more, compositions with approximately 440 mcg / mL or more, compositions with approximately 450 mcg / mL or more, compositions with approximately 460 mcg / mL or more,Compositions containing approximately 470 mcg / mL or more, approximately 480 mcg / mL or more, approximately 490 mcg / mL or more, approximately 500 mcg / mL or more, approximately 510 mcg / mL or more, approximately 520 mcg / mL or more, approximately 530 mcg / mL or more, approximately 540 mcg / mL or more, approximately 550 mcg / mL or more, approximately 560 mcg / mL or more, approximately 570 mcg / mL or more, approximately 580 mcg / mL or more, and approximately 590 mcg / mL. The above are compositions of approximately 600 mcg / mL or more, approximately 610 mcg / mL or more, approximately 620 mcg / mL or more, approximately 630 mcg / mL or more, approximately 640 mcg / mL or more, approximately 650 mcg / mL or more, approximately 660 mcg / mL or more, approximately 670 mcg / mL or more, approximately 680 mcg / mL or more, approximately 700 mcg / mL or more, approximately 710 mcg / mL or more, approximately 720 mcg / mL or more, and sets of approximately 730 mcg / mL. Compositions of approximately 740 mcg / mL or more, compositions of approximately 750 mcg / mL or more, compositions of approximately 760 mcg / mL or more, compositions of approximately 770 mcg / mL or more, compositions of approximately 780 mcg / mL or more, compositions of approximately 790 mcg / mL or more, compositions of approximately 800 mcg / mL or more, compositions of approximately 810 mcg / mL or more, compositions of approximately 820 mcg / mL or more, compositions of approximately 830 mcg / mL or more, compositions of approximately 840 mcg / mL or more, compositions of approximately 850 mcg / mL or more, compositions of approximately 860 mcg / mL It is present in amounts greater than or equal to L of composition, greater than or equal to approximately 870 mcg / mL of composition, greater than or equal to approximately 880 mcg / mL of composition, greater than or equal to approximately 890 mcg / mL of composition, greater than or equal to approximately 900 mcg / mL of composition, greater than or equal to approximately 910 mcg / mL of composition, greater than or equal to approximately 920 mcg / mL of composition, greater than or equal to approximately 930 mcg / mL of composition, greater than or equal to approximately 940 mcg / mL of composition, greater than or equal to approximately 950 mcg / mL of composition, greater than or equal to approximately 960 mcg / mL of composition, greater than or equal to approximately 970 mcg / mL of composition, and greater than or equal to approximately 980 mcg / mL of composition.

[0039] In some embodiments, hyaluronic acid is used in compositions ranging from approximately 1 mcg / mL to approximately 250 mcg / mL, approximately 10 mcg / mL to approximately 250 mcg / mL, approximately 10 mcg / mL to approximately 200 mcg / mL, approximately 10 mcg / mL to approximately 150 mcg / mL, approximately 10 mcg / mL to approximately 100 mcg / mL, approximately 25 mcg / mL to approximately 250 mcg / mL, and approximately 25 mcg / mL. Compositions containing approximately 200 mcg / mL, compositions containing approximately 25 mcg / mL to approximately 150 mcg / mL, compositions containing approximately 25 mcg / mL to approximately 100 mcg / mL, compositions containing approximately 50 mcg / mL to approximately 250 mcg / mL, compositions containing approximately 50 mcg / mL to approximately 200 mcg / mL, compositions containing approximately 50 mcg / mL to approximately 150 mcg / mL, compositions containing approximately 50 mcg / mL to approximately 100 mcg / mL, compositions containing approximately 75 mcg / mL Compositions of approximately 250 mcg / mL, compositions of approximately 75 mcg / mL to approximately 200 mcg / mL, compositions of approximately 75 mcg / mL to approximately 150 mcg / mL, compositions of approximately 75 mcg / mL to approximately 100 mcg / mL, compositions of approximately 100 mcg / mL to approximately 250 mcg / mL, compositions of approximately 100 mcg / mL to approximately 200 mcg / mL, compositions of approximately 100 mcg / mL to approximately 150 mcg / mL, approximately 150 mcg / mL The composition is present in amounts ranging from approximately 250 mcg / mL, approximately 200 mcg / mL to approximately 250 mcg / mL, approximately 60 mcg / mL to approximately 80 mcg / mL, approximately 50 mcg / mL to approximately 75 mcg / mL, approximately 25 mcg / mL to approximately 75 mcg / mL, approximately 10 mcg / mL to approximately 50 mcg / mL, or approximately 10 mcg / mL to approximately 25 mcg / mL.

[0040] In some embodiments, hyaluronic acid is used in compositions ranging from approximately 1 mcg / mL to approximately 500 mcg / mL, approximately 10 mcg / mL to approximately 500 mcg / mL, approximately 10 mcg / mL to approximately 450 mcg / mL, approximately 10 mcg / mL to approximately 400 mcg / mL, approximately 10 mcg / mL to approximately 350 mcg / mL, approximately 10 mcg / mL to approximately 300 mcg / mL, approximately 25 mcg / mL to approximately 500 mcg / mL, and approximately 25 mcg / mL to approximately 450 mcg / mL. Compositions, compositions of approximately 25 mcg / mL to approximately 400 mcg / mL, compositions of approximately 25 mcg / mL to approximately 350 mcg / mL, compositions of approximately 25 mcg / mL to approximately 300 mcg / mL, compositions of approximately 50 mcg / mL to approximately 500 mcg / mL, compositions of approximately 50 mcg / mL to approximately 450 mcg / mL, compositions of approximately 50 mcg / mL to approximately 400 mcg / mL, compositions of approximately 50 mcg / mL to approximately 350 mcg / mL, compositions of approximately 50 mcg / mL to approximately 300 mcg / mL, and sets of approximately 75 mcg / mL. Compositions containing approximately 500 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 450 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 400 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 350 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 300 mcg / mL, compositions containing approximately 100 mcg / mL to approximately 500 mcg / mL, compositions containing approximately 100 mcg / mL to approximately 450 mcg / mL, compositions containing approximately 100 mcg / mL to approximately 400 mcg / mL, compositions containing approximately 100 mcg / mL to approximately 350 mcg / mL composition, composition of approximately 100 mcg / mL to approximately 300 mcg / mL, composition of approximately 150 mcg / mL to approximately 500 mcg / mL, composition of approximately 150 mcg / mL to approximately 450 mcg / mL, composition of approximately 150 mcg / mL to approximately 400 mcg / mL, composition of approximately 150 mcg / mL to approximately 350 mcg / mL, composition of approximately 150 mcg / mL to approximately 300 mcg / mL, composition of approximately 200 mcg / mL to approximately 500 mcg / mL, composition of approximately 200 mcg / mL to approximately 450 mcg / mL,It exists in amounts ranging from approximately 200 mcg / mL to approximately 400 mcg / mL, approximately 200 mcg / mL to approximately 350 mcg / mL, approximately 200 mcg / mL to approximately 300 mcg / mL, or approximately 200 mcg / mL to approximately 250 mcg / mL.

[0041] In some embodiments, hyaluronic acid is used in compositions ranging from approximately 1 mcg / mL to approximately 750 mcg / mL, approximately 10 mcg / mL to approximately 750 mcg / mL, approximately 10 mcg / mL to approximately 700 mcg / mL, approximately 10 mcg / mL to approximately 650 mcg / mL, approximately 10 mcg / mL to approximately 600 mcg / mL, approximately 10 mcg / mL to approximately 550 mcg / mL, approximately 25 mcg / mL to approximately 750 mcg / mL, and approximately 25 mcg / mL to approximately 700 mcg / mL. Compositions, compositions of approximately 25 mcg / mL to approximately 650 mcg / mL, compositions of approximately 25 mcg / mL to approximately 600 mcg / mL, compositions of approximately 25 mcg / mL to approximately 550 mcg / mL, compositions of approximately 50 mcg / mL to approximately 750 mcg / mL, compositions of approximately 50 mcg / mL to approximately 700 mcg / mL, compositions of approximately 50 mcg / mL to approximately 650 mcg / mL, compositions of approximately 50 mcg / mL to approximately 600 mcg / mL, compositions of approximately 50 mcg / mL to approximately 550 mcg / mL, sets of approximately 75 mcg / mL Compositions containing approximately 750 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 700 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 650 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 600 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 550 mcg / mL, compositions containing approximately 100 mcg / mL to approximately 750 mcg / mL, compositions containing approximately 100 mcg / mL to approximately 700 mcg / mL, compositions containing approximately 100 mcg / mL to approximately 650 mcg / mL, compositions containing approximately 100 mcg / mL to approximately 600 mcg / mL composition, composition of approximately 100 mcg / mL to approximately 550 mcg / mL, composition of approximately 150 mcg / mL to approximately 750 mcg / mL, composition of approximately 150 mcg / mL to approximately 700 mcg / mL, composition of approximately 150 mcg / mL to approximately 650 mcg / mL, composition of approximately 150 mcg / mL to approximately 600 mcg / mL, composition of approximately 150 mcg / mL to approximately 550 mcg / mL, composition of approximately 200 mcg / mL to approximately 750 mcg / mL, composition of approximately 200 mcg / mL to approximately 700 mcg / mL,Compositions of approximately 200 mcg / mL to approximately 650 mcg / mL, compositions of approximately 200 mcg / mL to approximately 600 mcg / mL, compositions of approximately 200 mcg / mL to approximately 550 mcg / mL, compositions of approximately 300 mcg / mL to approximately 750 mcg / mL, compositions of approximately 300 mcg / mL to approximately 700 mcg / mL, compositions of approximately 300 mcg / mL to approximately 65 Compositions containing 0 mcg / mL, compositions containing approximately 300 mcg / mL to approximately 600 mcg / mL, compositions containing approximately 300 mcg / mL to approximately 550 mcg / mL, compositions containing approximately 400 mcg / mL to approximately 750 mcg / mL, compositions containing approximately 400 mcg / mL to approximately 700 mcg / mL, compositions containing approximately 400 mcg / mL to approximately 650 mcg / mL, and approximately 400 mcg Compositions ranging from approximately g / mL to about 600mcg / mL, from approximately 400mcg / mL to about 550mcg / mL, from approximately 500mcg / mL to about 750mcg / mL, from approximately 500mcg / mL to about 700mcg / mL, from approximately 500mcg / mL to about 650mcg / mL, and from approximately 500mcg / mL to about 600mcg / mL. The composition exists in amounts ranging from approximately 500 mcg / mL to approximately 550 mcg / mL, approximately 600 mcg / mL to approximately 750 mcg / mL, approximately 600 mcg / mL to approximately 700 mcg / mL, approximately 600 mcg / mL to approximately 650 mcg / mL, or approximately 700 mcg / mL to approximately 750 mcg / mL.

[0042] In some embodiments, hyaluronic acid is present in amounts of approximately 100 mcg / mL, approximately 200 mcg / mL, approximately 300 mcg / mL, approximately 400 mcg / mL, approximately 500 mcg / mL, approximately 600 mcg / mL, approximately 700 mcg / mL, approximately 800 mcg / mL, approximately 900 mcg / mL, approximately 1000 mcg / mL, or more.

[0043] In some embodiments, hyaluronic acid is used in compositions ranging from approximately 1 mcg / mL to approximately 950 mcg / mL, approximately 10 mcg / mL to approximately 950 mcg / mL, approximately 10 mcg / mL to approximately 900 mcg / mL, approximately 10 mcg / mL to approximately 850 mcg / mL, approximately 10 mcg / mL to approximately 800 mcg / mL, approximately 25 mcg / mL to approximately 950 mcg / mL, approximately 25 mcg / mL to approximately 900 mcg / mL, and approximately 25 mcg / mL to approximately 850 mcg / mL. Compositions containing approximately 25 mcg / mL to approximately 800 mcg / mL, compositions containing approximately 50 mcg / mL to approximately 950 mcg / mL, compositions containing approximately 50 mcg / mL to approximately 900 mcg / mL, compositions containing approximately 50 mcg / mL to approximately 850 mcg / mL, compositions containing approximately 50 mcg / mL to approximately 800 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 950 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 900 mcg / mL, compositions containing approximately 75 mcg / mL to approximately 850 mcg / mL, and compositions containing approximately 75 mcg / mL. Compositions of approximately 800 mcg / mL, compositions of approximately 100 mcg / mL to approximately 950 mcg / mL, compositions of approximately 100 mcg / mL to approximately 900 mcg / mL, compositions of approximately 100 mcg / mL to approximately 850 mcg / mL, compositions of approximately 100 mcg / mL to approximately 800 mcg / mL, compositions of approximately 150 mcg / mL to approximately 950 mcg / mL, compositions of approximately 150 mcg / mL to approximately 900 mcg / mL, compositions of approximately 150 mcg / mL to approximately 850 mcg / mL, compositions of approximately 150 mcg / mL to approximately 800 mcg Compositions of approximately 200 mcg / mL to approximately 950 mcg / mL, compositions of approximately 200 mcg / mL to approximately 900 mcg / mL, compositions of approximately 200 mcg / mL to approximately 850 mcg / mL, compositions of approximately 200 mcg / mL to approximately 800 mcg / mL, compositions of approximately 300 mcg / mL to approximately 950 mcg / mL, compositions of approximately 300 mcg / mL to approximately 900 mcg / mL, compositions of approximately 300 mcg / mL to approximately 850 mcg / mL, compositions of approximately 300 mcg / mL to approximately 800 mcg / mL,Compositions of approximately 400 mcg / mL to approximately 950 mcg / mL, compositions of approximately 400 mcg / mL to approximately 900 mcg / mL, compositions of approximately 400 mcg / mL to approximately 950 mcg / mL, compositions of approximately 400 mcg / mL to approximately 900 mcg / mL, compositions of approximately 400 mcg / mL to approximately 850 mcg / mL, compositions of approximately 400 mcg / mL to approximately 8 Compositions containing 00mcg / mL, compositions containing approximately 500mcg / mL to approximately 950mcg / mL, compositions containing approximately 500mcg / mL to approximately 900mcg / mL, compositions containing approximately 500mcg / mL to approximately 850mcg / mL, compositions containing approximately 500mcg / mL to approximately 800mcg / mL, compositions containing approximately 600mcg / mL to approximately 950mcg / mL, and approximately 600 Compositions of mcg / mL to approximately 900mcg / mL, compositions of approximately 600mcg / mL to approximately 850mcg / mL, compositions of approximately 600mcg / mL to approximately 600mcg / mL, compositions of approximately 700mcg / mL to approximately 950mcg / mL, compositions of approximately 700mcg / mL to approximately 900mcg / mL, compositions of approximately 700mcg / mL to approximately 850mc It exists in the following amounts: g / mL composition, composition of approximately 700mcg / mL to approximately 800mcg / mL composition, composition of approximately 800mcg / mL to approximately 950mcg / mL composition, composition of approximately 800mcg / mL to approximately 900mcg / mL composition, composition of approximately 800mcg / mL to approximately 850mcg / mL composition, composition of approximately 900mcg / mL to approximately 950mcg / mL composition, and approximately 1000mcg / mL.

[0044] In some embodiments, hyaluronic acid is present in amounts ranging from about 1 mg / mL to about 10 mg / mL of the composition. For example, hyaluronic acid may be present in amounts of about 1.0 mg / mL, about 1.1 mg / mL, about 1.2 mg / mL, about 1.3 mg / mL, about 1.4 mg / mL, about 1.5 mg / mL, about 1.6 mg / mL, about 1.7 mg / mL, about 1.8 mg / mL, about 1.9 mg / mL, about 2 mg / mL, about 2.1 mg / mL, about 2.2 mg / mL, about 2.3 mg / mL, about 2.4 mg / mL, about 2.5 mg / mL, about 2.6 mg / mL, about 2.7 mg / mL, about 2.8 mg / mL, about 2.9 mg / mL, about 3 mg / mL, about 3.1 mg / mL, about 3.2 mg / mL, about 3.3 mg / mL, and about 3.4 mg / mL. It is present in amounts of approximately 3.5 mg / mL, 3.6 mg / mL, 3.7 mg / mL, 3.8 mg / mL, 3.9 mg / mL, 4 mg / mL, 4.1 mg / mL, 4.2 mg / mL, 4.3 mg / mL, 4.4 mg / mL, 4.5 mg / mL, 4.6 mg / mL, 4.7 mg / mL, 4.8 mg / mL, 4.9 mg / mL, 5 mg / mL, 5.5 mg / mL, 6 mg / mL, 6.5 mg / mL, 7 mg / mL, 7.5 mg / mL, 8 mg / mL, 8.5 mg / mL, 9 mg / mL, 9.5 mg / mL, and 10 mg / mL or more.

[0045] In some embodiments, the compositions according to embodiments of the present invention include commercially available hyaluronic acid compositions. Suitable commercially available hyaluronic acid compositions include, but are not limited to, those sold under the trademarks JUVEDERM™, RESTYLANE-L™, CAPTIQUE™, BELOTERO BALANCE™, PREVELLE SILK™, ELEVESS™, HYLAFORM™, EUFLEXXA™, GEL-ONE™, HYALGAN™, ORTHOVISC™, MONOVISC™, SUPARTZ™, SYNVISC™, and SYNVISC-ONE™.

[0046] a. Polydispersion index (PDI) of hyaluronic acid As used herein, the term "polydispersity index (PD)" means, in the art, the number-average molecular weight M n (This is the weight-average molecular weight of each molecule multiplied by its corresponding molecular weight, i.e., the weight-statistical average molecular weight) w This characterizes the width of the molecular weight distribution curve with respect to the ratio of (the total weight of all polymer (hyaluronic acid) molecules in the sample divided by the total number of molecules). Generally, a smaller PDI value indicates a narrower molecular weight distribution range.

[0047] In some embodiments, hyaluronic acid analysis may be performed by size exclusion chromatography (SEC). In some embodiments, SEC may include separating the sample, monitoring the output with a concentration detector such as a refractive index detector or a UV absorbance detector, and comparing the elution time with the molecular weight. In some embodiments, hyaluronic acid analysis may include using a multi-angle light scattering (MALS) apparatus in series with the concentration detector. In some embodiments, the material properties of hyaluronic acid can be studied using a MALS apparatus, a differential refractive index detector, and a differential viscometer with SEC. Using a combination of these methods, information on the absolute molecular weight, molecular weight distribution, and radius of hyaluronic acid can be determined.

[0048] 2. Carriers and other additives In some embodiments, the composition includes a carrier medium. Such a carrier medium may be a biocompatible liquid suitable for injection into the skin of mammals. In some embodiments, the carrier medium includes physiological saline. In some embodiments, hyaluronic acid functions as both the carrier medium and the active ingredient.

[0049] In some embodiments, the composition comprises one or more additives. Such additives may include preservatives or biocides.

[0050] In some embodiments, the composition comprises a microemulsifier, a nanoemulsifier, solid lipid nanoparticles, a nanostructured lipid carrier, liposomes, or vesicles.

[0051] In some embodiments, the composition may contain fatty acids (e.g., oleic acid), esters of fatty acids and alcohols (e.g., isopropylmyristic acid, isopropyl palmitate, ethyl oleate), medium-chain triglycerides, triacetins, or terpenes (e.g., limonene, menthol, cineole). In some embodiments, the composition may also contain surfactants. For example, suitable surfactants include, but are not limited to, TWEEN® (polysorbates), CREMOPHOR® (a mixture of macrogol glycerol hydroxystearate, PEG-40 castor oil, and polyoxyethylene 40 hydrogenated castor oil), TRANSCUTOL® P (diethylene glycol monoethyl ether), PLUROL OLEIQUE® (polyglyceryl-3-oleate), PLUROL ISOSTARIQUE® (isostearate esters of polyglycerol and higher oligomers), and LABRASOL® (a mixture of mono-, di-, and triglycerides of C8 and C10 fatty acids, and mono- and diesters of PEG), and lecithin. In some embodiments, the composition may contain co-surfactants. For example, suitable co-surfactants include, but are not limited to, short-chain and medium-chain alcohols and polyglyceryl derivatives (including ethanol, isopropanol, isopropylmyristic acid, and propylene glycol).

[0052] In some embodiments, the composition comprises one or more of the following: soybean oil, jojoba oil, aloe vera oil, soybean phosphatidylcholine, water, polysorbate 80, ethanol, benzyl alcohol, isopropyl alcohol, glycerin, glyceryl monostearate, and propylene glycol.

[0053] II. Method This disclosure provides methods for treatment, methods for administration, and methods for preparing compositions. In some embodiments, the methods described in U.S. Patent No. 11,337,993 can be utilized in this disclosure (the contents of which are incorporated herein by reference in their entirety).

[0054] 1.Treatment method This disclosure provides a therapeutic method using the compositions described herein. Where used herein, the terms “to treat,” “treatment,” or “to treat” refer to a therapeutic act whose purpose is to reverse, alleviate, improve, inhibit, slow, or halt the progression or severity of a disease or condition, e.g., androgenic alopecia or other forms of alopecia. The term “to treat” includes reducing or alleviating at least one adverse effect or symptom of a disease or condition, e.g., androgenic alopecia or other forms of alopecia. A treatment may be considered effective if one or more symptoms are alleviated, e.g., if the rate of hair loss decreases. Alternatively, a treatment may be considered effective if the progression of the disease is reduced or halted. That is, the term “treatment” includes not only improvement of symptoms but also halting, or at least delaying, the progression or worsening of symptoms compared to what would be expected in the absence of treatment. Beneficial or desired clinical outcomes include, but are not limited to, the alleviation of one or more symptoms. A reduction in the severity of the disease, a stable (i.e., non-worsening) state of the disease, a delay or slowing of disease progression, improvement or alleviation of the disease state, and / or remission (either partial or complete). For example, if the degree or amount of hair loss is reduced, the progression of hair loss slows or stops, or hair regrowth is induced, the treatment is considered effective.

[0055] In some embodiments, the compositions of the present disclosure can be used to treat androgenetic alopecia (AGA). In some embodiments, the compositions of the present disclosure can improve one or more metrics related to AGA. In some embodiments, the compositions of the present disclosure may be used to treat hair loss in patients with AGA. In some embodiments, the compositions stimulate hair growth in patients with AGA.

[0056] Androgenetic alopecia (AGA) is a genetically predetermined disorder resulting from an excessive response to androgens, characterized by the progressive loss of terminal hairs on the scalp at any point after puberty, affecting up to 50% of men and women. Elevated levels of androgens, including the present dihydrotestosterone (DHT), lead to increased activation of androgen receptors on the hair follicles, which causes a shortening of the anagen phase of the normal hair cycle. Excessive activation results in miniaturization of the hair follicles through a progressively shorter anagen phase, leading to thinner and shorter hair follicles. In men, hair loss is most pronounced in the parietal and frontotemporal regions, while in women, hair loss typically occurs in the parietal region.

[0057] A method for stimulating hair growth in patients who require it includes administering a composition according to an embodiment of the present invention to the surface of or into the skin of the patient. A method for administering a composition for hair growth is also provided herein.

[0058] In some embodiments, the compositions of this disclosure may be administered to the skin of a patient. In some embodiments, the compositions are administered topically by applying the compositions to the surface of the patient's skin. In some embodiments, the compositions are administered to the dermis or subcutaneous tissue of the patient's skin, for example, by injection as described herein. In one embodiment, the compositions may be administered to the skin of a patient by intradermal injection.

[0059] The evaluation of hair growth in patients may be based on patient self-assessment, physician assessment using a standardized scale, global photographic assessment, target area hair count (TAHC), target area hair width (TAHW; also referred to herein as hair diameter measurement), average hair length measurement, average hair diameter measurement, and / or hair weight measurement. In one embodiment, the composition can improve or increase target area hair count (TAHC), TAHW, average hair length, average hair diameter, hair blackness, and / or hair weight. As used herein, target area hair count is measured over 1 cm on the patient's head. 2This refers to the number of hairs per unit area. In some embodiments, a higher TAHC value indicates better results. In some embodiments, the target area hair width (TAHW) may refer to the cumulative width of hairs in a region of the patient's scalp (target area) being treated with the composition of the present disclosure. A higher TAHW value indicates better results.

[0060] In some embodiments, the composition can improve or increase the target area hair count (TAHC), TAHW, average hair length, average hair diameter, hair blackness, and / or hair weight by about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, about 1-10%, 15-25%, 20-30%, 25-35%, 30-40%, 35-45%, 40-50%, 45-55%, 50-60%, 55-65%, 60-70%, 65-75%, 70-80%, 75-85%, 80-90%, and 85-95% or more. In some embodiments, the composition can improve or increase the target area hair count (TAHC), target area hair weight (TAHW), average hair length, average hair diameter, hair blackness, and / or hair weight by approximately 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 times or more.

[0061] Improvements or increases in target area hair count (TAHC), TAHW, average hair length, average hair diameter, hair blackness, and / or hair weight can be measured at any point in time after treatment with the compositions of the present disclosure. For example, after administration of the composition, improvements can be measured about 10 to 160 days after administration of the compound. In some embodiments, improvements can be measured after about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180 days, or longer.

[0062] In some embodiments, prior to treatment with the compositions of the Disclosure, the patient has experienced hair loss for about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 2 years, about 3 years, about 5 years, about 6 years, about 7 years, about 8 years, about 9 years, about 10 years or longer. In some embodiments, the patient has experienced hair loss for about 3 to about 5 years prior to administration of the compositions of the Disclosure.

[0063] In some embodiments, the patient has previously undergone a hair transplant procedure. In some embodiments, the patient has undergone hair transplants for approximately 1 to 2 months, 2 to 3 months, 3 to 4 months, 4 to 5 months, 5 to 6 months, 6 to 7 months, 7 to 8 months, 8 to 9 months, 9 to 10 months, 10 to 11 months, 11 to 12 months, or longer.

[0064] In some embodiments, the patient is either male or female.

[0065] In some embodiments, the patient has mild or moderate AGA.

[0066] In some embodiments, the patient receives a modified Norwood Hamilton scale score of I, II, IIa, III, III vertex, IIIa, IV, V, Iva, VI, VII, or Va. Characteristics associated with each modified Norwood Hamilton scale score are shown in the figure. In some embodiments, the patient receives a modified Norwood Hamilton scale score of III, or a modified Norwood Hamilton scale score of IV.

[0067] In some embodiments, a method for stimulating hair growth in a patient who requires it includes administering a composition according to an embodiment of the present invention to the surface of or into the skin of the patient. In some embodiments, the composition is administered topically by applying the composition to the surface of the patient's skin. In some embodiments, the composition is administered into the dermis or subcutaneous tissue of the patient's skin, for example, by injection as described herein.

[0068] In some embodiments, the composition according to the embodiments of the present invention is applied to the patient's skin once a day for one day, once a day for one week, once a day for one month, once a day for one year, twice a day for one day, twice a day for one week, twice a day for one month, twice a day for one year, once a week for one week, once a week for one month, once a week for one year, twice a week for one week, twice a week for one month, twice a week for one year, once a month for one month, once a month for two months, once a month for six months, once a month It is administered to the patient's skin for one year, twice a month for one month, twice a month for two months, twice a month for six months, twice a month for one year, once every two months for two months, once every two months for four months, once every two months for six months, once every two months for one year, once every three months for three months, once every three months for six months, once every three months for nine months, once every three months for one year, once every four months for four months, once every four months for eight months, once every four months for one year, once every six months for six months, once every six months for one year, or as needed.

[0069] In some embodiments, the composition is administered at least once a week, at least twice a week, at least three times a week, at least four times a week, at least five times a week, at least six times a week, at least seven times a week, or more. In some embodiments, the composition is administered on consecutive days of the week. In some embodiments, the composition is administered for about two consecutive days, about three consecutive days, about four consecutive days, about five consecutive days, about six consecutive days, or seven or more consecutive days. In some embodiments, the composition is administered every other day of the week. In a non-limiting example, the composition may be administered three times a week for three consecutive days.

[0070] As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid three times per week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the target skin at least twice per week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the target skin at least three times per week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the target skin at least four times per week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the target skin at least five times per week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the target skin at least six times per week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the target skin at least seven times per week.

[0071] As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid three times a week for three consecutive days. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the skin of a subject for two consecutive days at least twice a week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the skin of a subject for four consecutive days at least four times a week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the skin of a subject for five consecutive days at least five times a week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the skin of a subject for six consecutive days at least six times a week. As a non-limiting example, the method of the Disclosure may include administering up to 1% hyaluronic acid to the skin of a subject for seven consecutive days at least seven times a week.

[0072] As a non-limiting example, the method of this disclosure can be used to administer 0.3% hyaluronic acid three times a week for intradermal injection. As a non-limiting example, the method of this disclosure can be used to administer 0.4% hyaluronic acid three times a week for intradermal injection. As a non-limiting example, the method of this disclosure can be used to administer 0.2% hyaluronic acid three times a week for intradermal injection. As a non-limiting example, the method of this disclosure can be used to administer 0.3% hyaluronic acid three times a week for three consecutive days for intradermal injection. As a non-limiting example, the method of this disclosure can be used to administer 0.4% hyaluronic acid three times a week for three consecutive days for intradermal injection. As a non-limiting example, the method of this disclosure can be used to administer 0.2% hyaluronic acid three times a week for three consecutive days for intradermal injection.

[0073] 2. Administration A method for administering a composition according to an embodiment of the present invention involves delivering the composition according to an embodiment of the present invention to a hair follicle. In some embodiments, delivery is by topical administration, i.e., application of the composition to the surface of the skin and penetration of the composition into the skin. In some embodiments, the administration method includes a step to enhance penetration before topical administration of the composition. In some embodiments, delivery is by injection into the skin.

[0074] A method of administering a composition according to an embodiment of the present invention involves injecting a therapeutic dose of the composition into the skin of a patient in need of treatment. In some embodiments, the composition according to an embodiment of the present invention is administered as a bolus, which, as used herein, refers to a dosage delivered in less than 10 minutes. In some embodiments, the composition according to an embodiment of the present invention is administered as an infusion, which, as used herein, refers to a dosage delivered in about 10 minutes or more.

[0075] Such injections may be performed via a single needle, microneedle, or similar device, or via an array of needles, microneedles, or similar devices. In some embodiments, the composition according to embodiments of the present invention is delivered via a conventional syringe. In some embodiments, subcutaneous delivery is performed via a hollow microneedle syringe. In some embodiments, subcutaneous delivery is performed via a microneedle patch coated with the composition according to embodiments of the present invention (e.g., coated by 3D printing). In some embodiments, the composition is delivered via a jet syringe. As used herein, the term “needle” refers to any such device for penetrating the skin and injecting the composition according to embodiments of the present invention.

[0076] Preferably, the composition is administered near the patient's hair follicles. Therefore, in some embodiments, the composition is administered by injecting a therapeutic dose of the composition into the patient's dermis (intradermal injection).

[0077] In some embodiments, the composition is administered by injecting a therapeutic dose of the composition into the subcutaneous tissue of the patient. In some embodiments, the composition is administered into the patient's skin at a depth of about 0.4 mm to about 2 mm (i.e., about 0.4 mm to about 3 mm from the surface of the skin). In some embodiments, the composition is administered into the patient's skin at a depth of about 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm, about 1.9 mm, about 2 mm, about 2.1 mm, about 2.2 mm, about 2.3 mm, about 2.4 mm, about 2.5 mm, about 2.6 mm, about 2.7 mm, about 2.8 mm, about 2.9 mm, or about 3 mm. In some embodiments, the composition is applied to the patient's skin in the following sizes: approximately 0.1 mm to approximately 0.5 mm, approximately 0.1 mm to approximately 1 mm, approximately 0.5 mm to approximately 1 mm, approximately 1 mm to approximately 1.5 mm, approximately 1.5 mm to approximately 2 mm, approximately 2 mm to approximately 2.5 mm, approximately 2.5 mm to approximately 3 mm, approximately 1 mm to approximately 3 mm, approximately 1.5 mm to approximately 3 mm, approximately 0.4 mm to approximately 0.6 mm, and approximately 0.4 mm to approximately 0.8 mm. , about 0.4mm to about 1mm, about 0.4mm to about 1.2mm, about 0.4mm to about 1.4mm, about 0.4mm to about 1.6mm, about 0.4mm to about 1.8mm, about 0.4mm to about 2mm , about 0.4mm to about 2.2mm, about 0.4mm to about 2.4mm, about 0.4mm to about 2.6mm, about 0.4mm to about 2.8mm, about 0.4mm to about 3mm, about 0.6mm to about 0.8 mm, approx. 0.6mm to approx. 1mm, approx. 0.6mm to approx. 1.2mm, approx. 0.6mm to approx. 1.4mm, approx. 0.6mm to approx. 1.6mm, approx. 0.6mm to approx. 1.8mm, approx. 0.6mm to approx. 2mm, approx. 0.6mm to approx. 2.2mm, approx. 0.6mm to approx. 2.4mm, approx. 0.6mm to approx. 2.6mm, approx. 0.6mm to approx. 2.8mm, approx. 0.6mm to approx. 3mm, approx. 0.8mm to approx. 1mm, approximately 0.8mm to 1.2mm, approximately 0.8mm to 1.4mm, approximately 0.8mm to 1.6mm, approximately 0.8mm to 1.8mm, approximately 0.8mm to 2mm, approximately 0.8mm to 2.2mm, approximately 0.8mm to 2.4mm, approximately 0.8mm to 2.6mm, approximately 0.8mm to 2.8mm, approximately 0.8mm to 3mm, approximately 1mm to 1.2mm, approximately 1mm to 1.4mm, approx. 1mm-1.6mm, approx. 1mm-1.8mm, approx. 1mm-2mm, approx. 1mm-2.2mm, approx. 1mm-2.4mm, approx. 1mm-2.6mm, approx. 1mm-2.8mm, approx. 1mm-3mm, approx. 1.2mm-1.4mm, approx. 1.2mm-1.6mm, approx. 1.2mm-1.8mm, approx. 1.2mm-2mm, approx. 1.2mm-2.2mm, approx. 1.2mm-2.4mm , about 1.2mm to about 2.6mm, about 1.2mm to about 2.8mm, about 1.2mm to about 3mm, about 1.4mm to about 1.6mm, about 1.4mm to about 1.8mm, about 1.4mm to about 2mm, about 1.4mm to about 2.2mm, about 1.4mm to about 2.4mm, about 1.4mm to about 2.6mm, about 1.4mm to about 2.8mm, about 1.4mm to about 3mm, about 1.6mm to about 1.8mm, about 1.6mm to about 2mm, about 1. 6mm to approximately 2.2mm, approximately 1.6mm to approximately 2.4mm, approximately 1.6mm to approximately 2.6mm, approximately 1.6mm to approximately 2.8mm, approximately 1.6mm to approximately 3mm, approximately 1.8mm to approximately 2mm, approximately 1.8mm to approximately 2.2mm, approximately 1.8mm to approximately 2.4mm, approximately 1.8mm to approximately 2.6mm, approximately 1.8mm to approximately 2.8mm, approximately 1.8mm to approximately 3mm, approximately 2.0mm to approximately 2.2mm, approximately 2.0mm to approximately 2.4mm, approximately 2.0mm The formulation is administered in the following ranges: m to approximately 2.6 mm, approximately 2.0 mm to approximately 2.8 mm, approximately 2.0 mm to approximately 3 mm, approximately 2.2 mm to approximately 2.4 mm, approximately 2.2 mm to approximately 2.6 mm, approximately 2.2 mm to approximately 2.8 mm, approximately 2.2 mm to approximately 3 mm, approximately 2.4 mm to approximately 2.6 mm, approximately 2.4 mm to approximately 2.8 mm, approximately 2.4 mm to approximately 3 mm, approximately 2.6 mm to approximately 2.8 mm, approximately 2.6 mm to approximately 3 mm, or approximately 2.8 mm to approximately 3 mm. In some embodiments, the compositions of this disclosure are injected onto the skull.

[0078] In one embodiment, the injection depth may vary depending on the thickness of the scalp in different areas of the scalp. Different areas of the scalp may have different thicknesses. For example, the mean dermal thickness of the posterior scalp may be about 1443.86 μm, the thickness of the temporal scalp may be about 1349.52 μm, and / or the thickness of the anterior scalp may be about 1146.13 μm. In some embodiments, the injection depth may be about 0.7 mm to about 2 mm.

[0079] In one embodiment, the composition is administered adjacent to or proximal to the stem cell region of the hair follicle.

[0080] In some embodiments, the injection area is approximately 1 cm 2 Approximately 2cm 2 , about 3cm 2 , about 4cm 2 , about 5cm 2 Approximately 6cm 2 , about 7cm 2 , about 8cm 2 , about 9cm 2 , about 10cm 2 , about 15cm 2 , about 20cm 2 , about 25cm 2 , about 30cm 2 , about 35cm 2 , about 40cm 2 Approximately 45cm 2 , about 50cm 2 Approximately 55cm 2 , about 60cm 2 , about cm 2 , about 70cm 2 , about 75cm 2 , about 80cm 2 Approximately 85cm 2 , about 90cm 2 , about 95cm 2 , about 100cm 2 , 200cm 2 , 300cm 2 , 400cm 2 , 500cm 2 , 600cm 2 , 700cm 2 The above is possible. In one embodiment, the injection area can cover the entire area of ​​the target scalp.

[0081] The composition can be injected along a line approximately 0.2 to 0.3 cm apart. In some embodiments, the composition can be injected into lines approximately 1 cm apart.

[0082] In some embodiments, the composition according to the embodiments of the present invention can be administered by multiple injections. In some embodiments, the composition according to the embodiments of the present invention can be administered by about one injection / cm². 2 Skin: Approximately 1000 injections / cm² 2 Skin, approximately 200 injections / cm² 2 Skin: Approximately 800 injections / cm² 2 Injecting into the skin, or approximately 400 injections / cm² 2 Skin: Approximately 650 injections / cm² 2 It is administered via the skin. In some embodiments, the composition is administered at approximately 200 injections / cm³. 2 Skin, approximately 250 injections / cm 2 Skin, approximately 300 injections / cm 2 Skin, approximately 350 injections / cm 2 Skin, approximately 400 injections / cm 2 Skin, approximately 450 injections / cm 2 Skin, approximately 500 injections / cm 2 Skin, approximately 550 injections / cm 2 Skin, approximately 600 injections / cm 2 skin, or approximately 650 injections / cm 2 It is administered through the skin. The contents of U.S. Patent No. 11,337,993 are incorporated herein by reference.

[0083] The compositions of this disclosure can be administered to one or more areas of the scalp. For example, the compositions can be administered to the forehead (or central bangs), the central part of the scalp (or central posterior part of the scalp), the temporal scalp (lateral part), the parietal transition zone (or parietal transition point), and the crown (or crown). In some embodiments, the forehead and temporal regions of the scalp may be collectively referred to as the frontotemporal region. In one embodiment, the composition is administered to the frontotemporal region of the scalp.

[0084] In some embodiments, local delivery is performed after or in conjunction with iontophoresis. For example, iontophoresis is performed with a gentle current (e.g., 0.1-1.0 mA / cm²) to increase the skin penetration of the composition. 2This may include the application of ( ). Although not bound by theory, iontophoresis is thought to improve skin penetration by enhancing electromigration, electroosmosis, and / or passive diffusion.

[0085] In some embodiments, local delivery is performed after or in conjunction with the application of electroporation. For example, electroporation may involve the application of high-intensity, high-voltage (e.g., 50-1500V) short-duration (10 microseconds-10 milliseconds) electrical pulses to form aqueous pores in the lipid bilayer of the stratum corneum of the skin.

[0086] In some embodiments, local delivery is performed after or in conjunction with the application of sonophoresis. For example, sonophoresis may include the application of sound waves at high frequencies (e.g., about 500 kHz to 1250 kHz) or low frequencies (e.g., about 20 to about 100 kHz) or (starting at one of the high or low frequencies and progressing to the other).

[0087] In some embodiments, local delivery is performed after or in conjunction with the application of laser ablation. Laser ablation may involve generating photomechanical waves by laser ablation of a target material (e.g., a polymer) placed on the surface of the skin.

[0088] In some embodiments, local delivery is performed after or in conjunction with magnetophoresis. Magnetophoresis may include the application of a magnetic field, such as a pulsed electromagnetic field, to the skin.

[0089] In some embodiments, local delivery is performed after the application of radiofrequency thermal ablation. Thermal ablation may involve the application of extreme heat (e.g., about 300°C for microseconds) on the skin surface. While not bound by theory, it is thought that thermal ablation can evaporate a portion of the stratum corneum to form micron-scale channels. Thermal ablation can be achieved using commercially available equipment, including VIADOR® (Syneron Medical Ltd, Israel) and PASSPORT® (Nitto-Denko, Japan). In some embodiments, thermal ablation can be achieved using an erbium:yttrium-gallium-garnet (Er:YAG) laser with a wavelength of 2,790 nm or a yttrium-scandium-gallium-garnet (YSGG) laser with a wavelength of 2,940 nm. In some embodiments, segmented laser ablation may be applied to sub-millimeter areas to generate spots that mimic a microneedle array pattern (e.g., 40-300 mu.m at a density of 50-600 cm). In some embodiments, local delivery is performed after the application of the microneedle device.

[0090] 3. Manufacturing method The process for producing a composition according to embodiments of the present invention includes preparing an effective amount of hyaluronic acid. In some embodiments, the effective amount of hyaluronic acid may be further mixed with an effective amount of osteopontin. In some embodiments, the hyaluronic acid has an average molecular weight in the range of about 4,000 kDa to 10,000 kDa, about 10,000 kDa to about 100,000 kDa, about 15 kDa to about 50 kDa, about 75 kDa to about 350 kDa, or about 20 kDa to 1350 kDa. In some embodiments, the hyaluronic acid has an average molecular weight greater than about 950 kDa. In some embodiments, the effective amount of hyaluronic acid is mixed with an effective amount of CD44-binding ligand. The process may also include the step of preparing a physiologically acceptable carrier medium to which an active agent is added. In some embodiments, the physiologically acceptable carrier medium is injectable.

[0091] In some embodiments, the manufacturing method includes a step of forming a microemulsion or nanoemulsion. The microemulsion or nanoemulsion comprises oil, water, a surfactant, and a co-surfactant, and can form a colloidal dispersion with a droplet size in the range of about 10 nm to about 100 nm. In some embodiments, the microemulsion or nanoemulsion may contain fatty acids (e.g., oleic acid), esters of fatty acids with alcohols (e.g., isopropylmyristic acid, isopropyl palmitate, ethyl oleate), medium-chain triglycerides, triacetin, or terpenes (e.g., limonene, menthol, cineole). In some embodiments, the microemulsion or nanoemulsion may contain a surfactant. For example, suitable surfactants include, but are not limited to, TWEEN™ (polysorbate), CREMOPHOR™ (a mixture of macrogol glycerol hydroxystearate, PEG-40 castor oil, and polyoxyethylene-40 hydrogenated castor oil), TRANSCUTOL™ P (diethylene glycol monoethyl ether), PLUROL OLEIQUE™ (polyglyceryl-3-oleate), PLUROL ISOSTARIQUE™ (isostearate ester of polyglycerol and higher-degree-of-polymerization oligomers), and LABRASOL™ (a mixture of mono-, di-, and triglycerides of C8 and C10 fatty acids, and mono- and diesters of PEG), and lecithin. In some embodiments, the microemulsion or nanoemulsion may contain a co-surfactant. For example, suitable cosurfactants include, but are not limited to, short-chain and medium-chain alcohols and polyglyceryl derivatives (including ethanol, isopropanol, isopropylmyristic acid, and propylene glycol). In some embodiments, the formation of microemulsions or nanoemulsions involves the use of a high-pressure homogenizer, a microfluidizer, and / or an ultrasonic treatment device.

[0092] In some embodiments, the manufacturing method includes the step of mixing a composition according to an embodiment of the present invention with solid nanoparticles. The solid nanoparticles may include materials such as metal oxides (e.g., zinc oxide, titanium dioxide) or polymers that are solid at room temperature.

[0093] In some embodiments, the manufacturing method includes the step of mixing a composition according to an embodiment of the present invention with solid lipid nanoparticles. The solid lipid nanoparticles contain lipids that are solid at room temperature and have a surfactant surface coating that can stabilize them as droplets having a size of less than about 100 nm when dispersed in water.

[0094] In some embodiments, the manufacturing method includes a step of mixing a composition according to an embodiment of the present invention with a nanostructured lipid support. The nanostructured lipid support may include a fluid lipid phase embedded in a solid lipid matrix or localized on the surface of a plate-like crystal, and a surfactant layer.

[0095] In some embodiments, the manufacturing method includes a step of mixing a composition according to an embodiment of the present invention with liposomes. The liposomes may comprise spherical vesicles composed of amphiphilic phospholipids and cholesterol, which self-associate into multilayers, large monolayers, and small monolayer vesicles.

[0096] In some embodiments, the manufacturing method includes the step of mixing a composition according to an embodiment of the present invention with flexible vesicles. The flexible vesicles may include materials that associate into a bilayer structure, as well as components that impart flexibility. In some embodiments, the flexible vesicles include etosomes (i.e., phospholipids with a high proportion of ethanol), niosomes (i.e., nonionic surfactants), invasosomes (i.e., a mixture of phospholipids, ethanol, and terpene osmotherapeutics), SECosomes (i.e., surfactants, ethanol, and cholesterol), or PEVs (i.e., osmotherapeutic vesicles). In some embodiments, the PEVs may include oleic acid, limonene, or propylene glycol.

[0097] In some embodiments, the manufacturing method includes the step of mixing a composition according to an embodiment of the present invention with polymer micelles or polymer dendrimers. Polymer micelles may be colloidal carriers having a hydrophilic outer shell and a hydrophobic inner core. Polymer micelles may be nano-sized. Polymer dendrimers may include branched polymer structures.

[0098] Examples Example 1. Evaluation of hyaluronic acid (AMP-303) compared to physiological saline control in men with androgenetic alopecia. The validity of the research design Quantitative measurement of hair growth has become the standard in demonstrating the effectiveness of AGA hair growth products. To date, the dosage forms typically used to treat AGA are administered topically or orally. Intradermal injection may alter the topology / contour of the skin surface, hair orientation, or other features that may interfere with the imaging or accurate serial imaging of hair over time. This was evaluated to measure the impact of this administration route on the usefulness of standard hair count and related measures. The study will focus on evaluating what differences may occur between pre- and post-injection due to AMP-303 compared to a saline control over the study period. The topical safety effect of intradermal injection of AMP-303 compared to a saline control will be collected. Furthermore, this study will include three different groups of patients with androgenic alopecia to improve the study population for future research in androgenic alopecia.

[0099] Research products and formulations The research compound is hyaluronic acid for intradermal injection at a concentration of 0.3% ± 0.1% (also referred to herein as AMP-303).

[0100] AMP-303 for intradermal injection consists of non-crosslinked hyaluronic acid and phosphate-buffered saline.

[0101] The control, injectable sterile saline solution is phosphate-buffered saline.

[0102] Both the AMP-303 vehicle and the saline control are supplied as injectable solutions. Identical 1 mL syringes with 0.1 mL and 0.5 mL boundaries are used for both AMP-303 and the control. AMP-303 and the saline control are supplied as sterile products.

[0103] Research purpose The purpose of this study was to evaluate the safety and tolerability of AMP-303 injected into the dermis of the scalp compared to a saline control in men with androgenetic alopecia. This study also evaluates the effect (if any) of AMP-303 compared to a saline control on hair count assessment methods in men with androgenetic alopecia. Furthermore, this study will be used to refine the intended use population.

[0104] research design This study is a prospective, multicenter, randomized, saline-controlled, non-significant risk (NSR) early feasibility study.

[0105] The administration plan involves intradermal injection of up to 2 mL of AMP-303 and a saline control, administered over three consecutive days.

[0106] The study will be randomized on day 0 at each clinical trial site. Participants will be randomly assigned to receive AMP-303 on either the right or left side and a saline control on the opposite side. All participants will receive intradermal injections of AMP-303 vehicle and saline control in the frontotemporal region of the scalp on days 0, 1, and 2. Participants will receive AMP-303 on one side of the frontotemporal region and saline control on the other side. The injection area will be up to approximately 4 cm², and the injection volume will be up to 2 mL per injection area. Injections will be limited to the frontotemporal region of the scalp. Each participant is expected to remain in the study for up to approximately 6 months (from screening to completion).

[0107] The appointment schedule is as follows: Visit 1: Screening (Day 30 to Day 1) Visit 2: Day 0 (Injection / Baseline) Visit 3: Day 1 (Injection) Visit 4: Day 2 (Injection) Visit 5: Day 14 (±3 days) Visit 6: Day 30 (±7 days) Visit 7: Day 60 (±7 days) Visit 8: Day 90 (±7 days) Visit 9: Day 120 (±7 days) Visit 10: Day 150 (±7 days)

[0108] Approximately 36 participants (12 participants per group) will be enrolled in this study at up to three clinical trial sites.

[0109] Three different groups will be enrolled in the study, with approximately 12 male subjects in each group: 1) recent onset of alopecia (defined as a history of alopecia of approximately 3–5 years); 2) established alopecia (defined as a history of alopecia of more than 10 years); and 3) post-transplant. Group 3 will enroll subjects who have completed hair transplantation procedures including bilateral frontotemporal regions. Eligible subjects must (1) be 1–2 months post-transplant, (2) have not shown significant post-transplant healing progress, and (3) have no active adverse events or medical concerns in the designated post-transplant injection area.

[0110] On day 0, eligible subjects will be randomized to receive AMP-303 in either the right or left frontotemporal region and a saline control in the opposite region ("injection site"). AMP-303 and the saline control will be administered intradermally by the principal investigator at each randomization visit on days 0, 1, and 2. Physicians, research staff, and subjects will be blinded to the research product injected into each side. Subjects who discontinue the study will not be replaced.

[0111] Potential benefits and risks The benefits of intradermal injection of the AMP-303 vehicle and this study include gathering information on the safety and tolerability of the vehicle for future research products, determining any effects on hair count assessment due to potential surface topology effects associated with intradermal injection of the AMP-303 vehicle and saline control, and refining the intended population for future studies. Potential risks associated with needle injection into the skin include injection site pain, erythema, bruising, and edema. These events are expected as a result of intradermal injection of AMP-303 or saline control; however, if any particular reaction or effect is more severe or occurs more frequently than expected, its occurrence may be considered an adverse event (AE).

[0112] Minimizing expected risks Under this protocol, risks are minimized as follows: 1) 4cm 2 1) Limited injection area on the scalp consisting of the following total area; 2) Low molecular weight non-crosslinked hyaluronic acid; 3) Limited to intradermal injection at a depth of approximately 0.6 mm to 0.8 mm; careful consideration of the anatomical structure of the scalp; 4) AMP-303 and saline control are provided as sterile products in the syringe used for injection; 5) The syringe is operated by a physician with experience in intradermal injection; 6) Standard precautions regarding injectable materials are followed; and / or 7) Only male subjects are enrolled.

[0113] Inclusion criteria The following are the criteria for entering the research. 1. Male adults aged 18 to 45 at the time of consent. 2. Clinical diagnosis of mild to moderate androgenetic alopecia (AGA) in the temples and parietal regions with a score of III or IV on the modified Norwood Hamilton Scale in subjects with approximately 3 to 5 years since the onset of hair loss, or at least 10 years since the onset of hair loss, or with recent hair transplants in the bilateral frontotemporal region. 3. Throughout the study, I hope to maintain the same hairstyle, hair length, and hair color. 4. You agree to continue using your usual hair care products and regimen for at least two weeks prior to day 4.0, and throughout the study. 5. I consent to having the hair around the injection site shaved at the time of screening and at each follow-up visit. 6. I agree to have my picture taken in a way that allows me to be identified. 7. Written informed consent was obtained before any research-related action was taken. 8. Written authorization for the use and publication of health and research information. 9. The likelihood of being able to follow research instructions, complete research assessment tools independently, and complete all required hospital visits.

[0114] Exclusion criteria The following are the criteria for exclusion from participation in the study. 1. Any uncontrolled systemic disease. 2. A history of positive results for human immunodeficiency virus (HIV) or active hepatitis B or C. 3. A history or current evidence of drug or alcohol abuse within 12 months prior to the screening visit. 4. Visible inflammatory skin disease, injury, or condition of the scalp in the injection area. 5. A history of known or suspected malignant tumors (other than non-melanoma skin cancer); treatment with chemotherapy or cytotoxic agents; or irradiation of the scalp. 6. Any skin conditions of the scalp on areas of baldness and thinning hair that could interfere with the study injection or study evaluation, such as fungal or bacterial infection, seborrheic dermatitis, psoriasis, eczema, folliculitis, scarring, skin cancer, tattoos, or scalp atrophy. 7. A medical history or active hair loss resulting from any condition other than AGA (e.g., diffuse telogen effluvium, alopecia areata, scarring alopecia, trichotillomania, or other genetic disorders, but not limited to these). 8. In the opinion of the principal investigator, a history of severe dietary changes, weight changes, or eating disorders that resulted in hair loss within six months prior to the screening visit. 9. Significant trauma with scalp reduction and associated scarring, previous hair transplants (groups 1 and 2), hair weave, and / or platelet-rich plasma (PRP) treatment on the scalp. 10. The subjects are using any other systemic therapy that, in the opinion of the principal investigator, could substantially affect their hair growth, including, but not limited to, hair growth or hair health products in the form of vitamins or homeopathic supplements, or other steroid hormones (in any form), including anabolic steroids. 11. Any of the following topical preparations or treatments performed on the scalp during a specific period prior to day 11.0 (baseline) 4 weeks: Over-the-counter (OTC) topical scalp or cosmetic treatments that may affect hair growth (e.g., brands such as Aminexil, Maxilene, Nioxin, and Foltene); hair growth products containing saw palmetto, copper, etc., including hair growth devices such as Cappilus, Revian, and Theradome; and / or, but not limited to, topical scalp treatments that may have an adjunct effect on hair growth, including corticosteroids, pimecrolimus, tacrolimus, and retinoids. 12 weeks: Topical scalp treatment for hair growth may include minoxidil, hormone therapy, anti-androgens, or other medications known to affect hair growth. 6 months: Laser, light source or energy therapy, or micropuncture of the scalp; oral retinoids, isotretinoin. 12. Any of the following systemic medications or procedures performed within a specific period prior to day 12.0 (baseline). 12 weeks: Within 12 weeks of visit 2 / baseline, beta-blockers, cimetidine, diazoxide, or corticosteroids (including intramuscular and intrafocal injections). If use is stable, inhaled, intranasal, or ocular corticosteroids are acceptable. Stability is defined as no change in dose and frequency for at least 4 weeks prior to visit 2 / baseline. 6 months: 5α-reductase inhibitors, e.g., finasteride (e.g., Propecia®) or dutasteride; retinoids, isotretinoin, vitamin A intake of approximately 10,000 IU per day, or cyclosporine therapy; and / or minoxidil. 13. Known hypersensitivity to any component of the research product (AMP-303 vehicle or sterile saline solution). 14. The subjects are known, or unlikely to be known, to not comply with the requirements of the study protocol, in the opinion of the principal investigator. 15. Current enrollment in an investigational drug or device study, or participation in such a study within 30 days of participation in this study. 16. In the opinion of the principal investigator, any patient has or is in a condition that could expose the patient to significant risk, interfere with the study results, or significantly hinder the patient's participation in the study.

[0115] Injection The injection will be limited to the frontotemporal region of the scalp. On day 0, eligible subjects will be randomized to receive an injection (either AMP-303 or saline control) in either the right or left treatment area. Standard injection site preparation will be performed (e.g., clean and wipe with alcohol). The same injection technique will be used for each subject on each day (days 0, 1, and 2).

[0116] Response evaluation items: The response endpoints to be evaluated include adverse events (including injection-related adverse events), local skin reactions: erythema, edema, and severity of contusions (none, minimal, mild, moderate, severe), which will be assessed by the principal investigator, and pain, itching, and burning / stinging sensations, which will be assessed by the subjects.

[0117] Vital signs such as blood pressure, pulse rate, and respiratory rate are also measured.

[0118] Other response measures include digital image analysis of non-vellus hair photographs; target area hair count (TAHC); target area hair width (TAHW); and / or hair darkness.

[0119] Standardized photography and digital image analysis (DIA) Qualified vendors take photographs and provide instructions for processing digital images. Typical macro photography of thinning hair areas (1cm) 2 Obtain a target area and record and measure the length, width, growth rate (growth phase / resting phase ratio), follicle unit ratio, and color of scalp hair. Use digital image analysis of the photographs to calculate the target area hair count (TAHC), target area hair width (TAHW), and hair blackness.

[0120] The modified Norwood-Hamilton classification is used to categorize the stages of male androgenetic alopecia (Figure) and to determine eligibility.

[0121] Statistical treatment Descriptive statistics are reported for all endpoints. Descriptive statistics vary depending on the type of variable. Generally, they include continuous variables: descriptive statistics include the number of observations, mean, median, standard deviation, minimum, maximum, and 95% confidence interval. Categorical variables include descriptive statistics including the number within a category, total number of observations, percentage of subjects within each category, and 95% confidence interval.

[0122] Visit to the hospital and related procedures Evaluations will, to the greatest extent possible, be conducted by the same evaluators throughout the entire study.

[0123] Visit 1: Screening (Day 30 to Day 1) Screening visits can be made at any point between 30 days and 1 day prior to the baseline visit. After obtaining informed consent, procedures performed may include: inclusion / exclusion criteria; demographics; Fitzpatricks dermatological classification; medical / surgical history; history of androgenetic alopecia; modified Norwood-Hamilton classification; concomitant medications and concurrent treatments; vital signs; standardized photographs; and review of the patient's instructions.

[0124] Visit 2: Baseline and injection (Day 0) If discontinuation from prohibited medication is not required, screening and day 0 may be performed on the same day. Information on changes in health status, concomitant medications, and concurrent treatments will be collected from the patient at any point during their visit. The order of events will include: inclusion / exclusion criteria (to confirm eligibility); vital signs; standardized photographs (to be completed after the above assessment); randomization; intradermal injection; local skin reactions (before and approximately 15 minutes after injection); and adverse events.

[0125] Visit 3: Day 1 At any point during the patient's visit, collect information from the patient regarding adverse events, concomitant medications, and concurrent treatments. Measure vital signs, followed by intradermal injection and local skin reactions (before injection and approximately 15 minutes after injection).

[0126] Visit 4: Day 2 At any point during the patient's visit, collect information from the patient regarding adverse events, concomitant medications, and concurrent treatments. Measure vital signs, then administer the intradermal injection; measure local skin reactions (before injection and approximately 15 minutes after injection).

[0127] Visit 5: Day 14 (±3 days) At any point during the patient's visit, collect information from the patient regarding adverse events, concomitant medications, and concurrent treatments. Measure vital signs, followed by local skin reactions and standardized photographs.

[0128] Visit 6: Day 30 (±7 days) At any point during the patient's visit, collect information from the patient regarding adverse events, concomitant medications, and concurrent treatments. Measure vital signs, followed by local skin reactions and standardized photographs.

[0129] Visit 7: Day 60 (±7 days) Information regarding adverse events, concomitant medications, and concurrent treatments will be collected from the patient at any point during their visit.

[0130] Vital signs are measured, followed by local skin reactions and standardized photography.

[0131] Visit 8: Day 90 (±7 days) At any point during the patient's visit, collect information from the patient regarding adverse events, concomitant medications, and concurrent treatments. Measure vital signs, followed by local skin reactions and standardized photographs.

[0132] Visit 9: Day 120 (±7 days) Information regarding adverse events, concomitant medications, and concurrent treatments will be collected from the patient at any point during their visit.

[0133] Vital signs are measured, followed by local skin reactions and standardized photography.

[0134] Visit 10: Day 150 (±7 days) Information regarding adverse events, concomitant medications, and concurrent treatments will be collected from the patient at any point during their visit.

[0135] Vital signs are measured, followed by local skin reactions and standardized photography. The subject then leaves the study.

[0136] Those skilled in the art will understand that modifications can be made to the exemplary embodiments shown and described above without departing from the broad inventive concept of the present invention. Therefore, it will be understood that the present invention is not limited to the illustrated and described exemplary embodiments, but is intended to encompass modifications within the spirit and scope of the invention as defined by the claims. For example, certain features of the exemplary embodiments may or may not be part of the claimed invention, and various features of the disclosed embodiments may be combined. Unless specifically stated herein, the terms “a,” “an,” and “the” should be read as meaning “at least one,” rather than being limited to a single element.

[0137] Furthermore, unless the method of the present invention depends on a specific order of steps described herein, no specific order of steps should be construed as a limitation to the claims. Any claim relating to the method of the present invention should not be limited to carrying out those steps in the order described, and those skilled in the art will readily understand that the steps may be varied and still fall within the spirit and scope of the invention.

Claims

1. A method for treating androgenetic alopecia (AGA) in patients who require it, The procedure involves administering a composition containing up to approximately 1% by weight of hyaluronic acid to the skin of the patient at least twice a week. The aforementioned hyaluronic acid is not cross-linked. The hyaluronic acid mentioned above contains an average molecular weight of up to approximately 100 kDa. Methods that include treating AGA (androgenetic alopecia) as a result.

2. The method according to claim 1, wherein the composition is administered to the patient on consecutive days of the week.

3. The method according to claim 1, wherein the composition is administered by intradermal injection.

4. The method according to claim 3, wherein the composition is injected to a depth of about 0.1 mm or more in the skin.

5. The method according to claim 3, wherein the composition is administered to or proximal to the stem cell region of a hair follicle.

6. Approximately 4cm ２ The method according to claim 1, comprising the injection area described above.

7. The method according to claim 1, wherein the composition is administered to the skin, which includes one or more of the frontotemporal region and the parietal region of the patient's scalp.

8. Treatment with the aforementioned composition a) Target area hair count (TAHC); b) Target area hair width (TAHW); and c) The method according to claim 1, which improves or increases one or more aspects of hair blackness.

9. The method according to claim 1, wherein the onset of hair loss in the patient occurs approximately 3 to 5 years before the administration of the composition.

10. The method according to claim 1, wherein the onset of hair loss in the patient occurs approximately 10 years before the administration of the composition.

11. The method according to claim 1, wherein the patient has previously undergone a hair transplant.

12. The method according to claim 11, wherein the patient has undergone the hair transplant approximately one to two months prior to the administration of the composition.

13. The method according to claim 1, wherein the AGA is mild or moderate.

14. The method according to claim 1, wherein the patient has a modified Norwood Hamilton Scale score of III or a modified Norwood Hamilton Scale score of IV.

15. The method according to claim 8, wherein the improvement or increase is measured approximately 10 to 160 days after administration of the composition.

16. The method according to claim 1, wherein the patient has previously experienced hair loss.

17. The method according to claim 7, wherein the hyaluronic acid stimulates hair growth in the frontotemporal region and / or the parietal region of the scalp of the patient.

18. A method for stimulating hair growth in the skin of a patient who needs it, The procedure involves administering a composition containing up to approximately 1% by weight of hyaluronic acid to the skin of the patient at least twice a week. The aforementioned hyaluronic acid is not cross-linked. The hyaluronic acid mentioned above contains an average molecular weight of up to approximately 100 kDa. A method comprising stimulating hair growth on the skin of the patient.

19. A method for administering a hair growth composition to a patient in need thereof, The procedure involves administering a composition containing up to approximately 1% by weight of hyaluronic acid to the skin of the patient at least twice a week. The aforementioned hyaluronic acid is not cross-linked. A method in which hyaluronic acid contains an average molecular weight of up to approximately 100 kDa.

20. The method according to claim 18 or 19, wherein the composition is administered to the patient on consecutive days of the week.

21. The method according to claim 18 or 19, wherein the composition is administered by intradermal injection.

22. The method according to claim 21, wherein the composition is injected to a depth of about 0.1 mm or more in the skin.

23. The method according to claim 21, wherein the composition is administered to or proximal to the stem cell region of a hair follicle.

24. Approximately 4cm ２ The method according to claim 18 or 19, comprising the injection area described above.

25. The method according to claim 18 or 19, wherein the composition is administered to the skin, which includes one or more of the frontotemporal region and the parietal region of the patient's scalp.

26. The composition is a) Target area hair count (TAHC); b) Target area hair width (TAHW); and c) The method according to claim 18 or 19, which improves or increases one or more aspects of hair blackness.

27. The method according to claim 18 or 19, wherein the onset of hair loss in the patient occurs approximately 3 to 5 years before the administration of the composition.

28. The method according to claim 18 or 19, wherein the onset of hair loss in the patient occurs approximately 10 years before the administration of the composition.

29. The method according to claim 18 or 19, wherein the patient has previously undergone a hair transplant.

30. The method according to claim 29, wherein the patient has undergone the hair transplant approximately one to two months prior to the administration of the composition.

31. The method according to claim 18 or 19, wherein the patient suffers from androgenetic alopecia (AGA).

32. The method according to claim 31, wherein the AGA is mild to moderate.

33. The method according to claim 18 or 19, wherein the patient has a modified Norwood Hamilton Scale score of III or a modified Norwood Hamilton Scale score of IV.

34. The method according to claim 26, wherein the improvement or increase is measured approximately 10 to 160 days after administration of the composition.

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