Systems and methods for treating sebaceous hyperplasia

Abstract

A method of treating Sebaceous Hyperplasia (SH) using a 1726 nm laser pulse that selectively targets sebum produced by the sebaceous glands.

Description

SYSTEMS AND METHODS FOR TREATING SEBACEOUS HYPERPLASIARELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Application No. 63 / 661 ,355 filed on June 18, 2024, the entire contents of which are incorporated herein by reference.FIELD

[0002] The present disclosure relates to a method of treating Sebaceous Hyperplasia (SH) using a 1726 nm laser pulse that selectively targets sebum produced by the sebaceous glands.BACKGROUND

[0003] This invention relates generally to electromagnetic radiation-based medical treatment systems, and more specifically to delivering a laser pulse selectively to sebaceous glands in the treatment of Sebaceous Hyperplasia (SH).

[0004] Sebaceous hyperplasia (SH) is a prevalent benign skin condition characterized by the enlargement of sebaceous glands. These glands, which are responsible for producing sebum to lubricate the skin and hair, can become enlarged due to various factors, including hormonal changes, genetic predisposition, and sun exposure. Although these glands are normal in structure, hyperplastic glands show increased numbers and size of the sebaceous lobules (Farci, Fabiola and Ronald P. Rapini “Sebaceous Hyperplasia.” StatPearls, StatPearls Publishing, 4 September 2023).

[0005] Clinically, SH presents as small, yellowish or flesh-colored papules on the skin, typically with a central dell or pore. These papules are most commonly found on the face, particularly on the forehead, nose, and cheeks, although they can also occur on the chest, back, and other areas with high sebaceous gland density.

[0006] While SH is generally asymptomatic, it can cause cosmetic concerns for affected individuals, leading to a desire for treatment. Current treatment options for SH include topical therapies, such as retinoids or chemical peels.

[0007] There is a need for a treatment method that is selective for sebaceous glands and be able to treat SH effectively.SUMMARY

[0008] The embodiments of the present disclosure provide a method of treating Sebaceous Hyperplasia (SH) in a patient comprising irradiating a sebum or a sebaceous gland with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, and continuing said treatment until SH lesions has reduced or cleared, and wherein the treatment resulted in a reduction of the size of SH lesions and a reduction in the number of SH lesions.

[0009] The embodiments of the present disclosure provide a method of treating SH in a patient comprising irradiating a sebum or a sebaceous gland with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, wherein the treatment reduces the size or clears the SH lesion(s) after treatment.

[0010] In certain embodiments and as used herein, the wavelength of about 1726 nm can be a wavelength from 1710 nm to 1735 nm. In certain embodiments, the wavelength can be from 1720 nm to 1730 nm. In other embodiments, the wavelength is plus or minus 10 nm from 1726 nm.

[0011] In one embodiment, the SH lesion is cleared within 8 weeks of treatment, or within 10 weeks of treatment, or within 12 weeks of treatment.

[0012] In one embodiment, the SH lesion is substantially or partially reduced in size within 4 or 6 or 8 or 10 weeks of treatment.

[0013] In the methods of the disclosure, the patient has one SH lesion.

[0014] In the methods of the disclosure, the patient has at least two SH lesions.

[0015] In some aspects, the patient received up to two treatments per SH lesion. In one embodiment, the treatments are spaced from about 2 to about 12 weeks apart. In another embodiment, the second treatment is from about 4 to about 16 weeks after the initial treatment.

[0016] In some aspects, the treatment resulted in a median improvement score of 2 on a 3-point scale.

[0017] In some aspects, the treatment resulted in a median improvement score of 3 on a 3-point scale.

[0018] In one aspect, the treatment results in a 4 or a 5 on the Global Aesthetic Improvement Scale (GAIS).

[0019] In some aspects, the sebaceous gland density is significantly increased after the treatment.

[0020] In some aspects, the sebaceous glands have longer thermal relaxation times due to increased density.

[0021] In some embodiments, the treatment results in a reduction in lesion size from about 2 mm to about 2.5 mm.

[0022] In other embodiments, the treatment results in clearance of the SH lesion.

[0023] In some embodiments, the treatment results in a reduction in lesion size of from about 0.2 mm to about 2.5 mm.

[0024] In some aspects, the sebaceous glands are more superficial.

[0025] In some aspects, the treatment was done with fluences from 24 J / cm2to 30 J / cm2range (short pulse). In one aspect, the treatment is done with fluences from about 5 J / cm2to about 30 J / cm2.

[0026] In some aspects, the skin shows no sign of indentation or scarring after the treatment.

[0027] In one aspect, the sebaceous gland density is significantly decreased after the treatment.

[0028] In some aspects, the treatment is done with longer, more energetic pulse with reduced cooling.

[0029] In some aspects, the treatment is safer and is less painful.

[0030] The treatment disclosed herein applies to patients with Fitzpatrick skin types I- VI.

[0031] The patient undergoing the treatment disclosed herein is 12 years of age or older.

[0032] In some aspects, the patient is aged between 12 and 80 years.

[0033] In one aspect, provided herein are methods of treating Sebaceous Hyperplasia (SH) in a patient comprising irradiating a sebum or a sebaceous gland that is an SH lesion with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, and wherein the treatment resulted in a reduction of the size or clearance of SH lesions.

[0034] In one embodiment, the patient has at least one or at least two SH lesions.

[0035] In one embodiment, the patient received up to three treatments per SH lesion.

[0036] In one embodiment, the treatment resulted in 4 or 5 on the Global Aesthetic Improvement Scale (GAIS).

[0037] In one embodiment, the treatment resulted in a reduction in lesion size from about 2 mm to about 2.5 mm.

[0038] In one embodiment, the treatment resulted in clearance of the lesion.

[0039] In one embodiment, wherein the sebaceous gland density is significantly decreased after the treatment.

[0040] In one embodiment, the sebaceous glands are more superficial.

[0041] In one embodiment, the treatment was done with fluences from 24 J / cm2to 30 J / cm2range or from about 5 J / cm2to about 30 J / cm2range.

[0042] In one embodiment, the skin shows no sign of indentation or scarring after the treatment.

[0043] In one embodiment, the treatment is done with longer, more energetic pulse with cooling from about 1 degree C to about 5 degress C.

[0044] In one embodiment, the laser pulse is delivered from the therapeutic laser is from about 5 W to about 90 W of power, from about 10 W to about 40 W of power, or from about 20 W to about 50 W of power.

[0045] In one embodiment, the SH lesion or lesions are treated with a single or double pulse of the therapeutic laser.

[0046] In one embodiment, the patient’s entire face is treated with the therapeutic laser.

[0047] In one embodiment, pulse duration of the therapeutic laser is a single or double pulse is up to 500 ms, from about 1 ms to about 500 ms, from about 5 ms to about 50 ms, or from about 10 ms to about 400 ms.

[0048] In one embodiment, the spot size of the therapeutic laser pulse is from about 3 mm2to about 9 mm2or from about 3 mm2to about 36 mm2or from about 0.08 mm2to about 9 mm2.

[0049] In one embodiment, the spot is circular or square in shape.

[0050] In one embodiment, the laser pulse is delivered from a laser having power from about 5 W to about 90 W.

[0051] Provided herein are methods of treating Sebaceous Hyperplasia (SH) in a patient comprising: irradiating a sebaceous hyperplasia lesion with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, and irradiating the sebaceous hyperplasia lesion a second time within 8 weeks, and wherein the treatment resulted in a reduction of the size or clearance of the SH lesion.BRIEF DESCRIPTION OF THE DRAWINGS

[0052] FIG. 1 is a flow chart of the treatment cycle.

[0053] FIG. 2 is a flowchart for classification of adverse device effects.

[0054] FIG. 3 is a 11 -point VAS Pain Rating Scale.

[0055] FIG. 4A is a photograph of sebaceous glands before treatment of SH lesion (baseline). Fig. 4B is a photograph of sebaceous glands after treatment of SH lesion.

[0056] FIG. 5A is a diagram of 2x2 treatment pattern or spots for the large handpiece. FIG. 5B is a diagram of 5x5 treatment pattern or spots for the large handpiece.DETAILED DESCRIPTION

[0057] Exemplary embodiments of the present disclosure are illustrated in the drawings, which are illustrative rather than restrictive. No limitation on the scope of the technology, or on the claims that follow, is to be implied or inferred from the examples shown in the drawings and discussed herein.

[0058] Sebaceous hyperplasia (SH) is a prevalent benign skin condition characterized by the enlargement of sebaceous glands. Single or multiple lesions manifest as yellowish, soft, small papules on the face.

[0059] SH affects approximately 1 % of the healthy population. SH is common in aging adults, with facial papules beginning to appear in middle age and continuing into later life. SH is more common in males.

[0060] The traditional treatment for SH include isotretinoin, acid peel, carbon dioxide lasers, cryotherapy, electrodessication and nano pulse stimulation. All these therapies are painful and have a high incidence of scarring and pigmentary change.

[0061] Laser therapy has emerged as a promising modality for the treatment of SH due to its ability to target and reduce the size of enlarged sebaceous glands effectively (Winstanley, Douglas et al. “Treatment of sebaceous hyperplasia with a novel 1 ,720-nm laser.” Journal of drugs in dermatology: JDD vol. 11 ,11 (2012): 1323-6; No, David, Marla McClaren, Vera Chotzen, and Suzanne L. Kilmer."Sebaceous Hyperplasia Treated With a 1450-nm Diode Laser." Dermatologic Surgery 30.3 (2004)). By delivering precise wavelengths of light to the affected areas, laser therapy can selectively heat and destroy the overactive sebaceous glands (Anderson, R.R, and J A Parrish. “Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation.” Science (New York, N.Y.)vol. 220,4596 (1983): 524-7) leading to an improvement in the appearance of SH lesions.

[0062] Currently, the 1726 Laser System is established as a safe and effective treatment for long-term management of mild to severe inflammatory acne vulgaris by regulating sebum production (Goldberg, David J et al. “Treatment of mild to severe acne with 1726 nm laser: A safe alternative to traditional acne therapies.” Journal of cosmetic dermatology vol. 22,11 (2023): 3026-3032). Nevertheless, further research is necessary to assess the potential of the 1726 Laser System in reducing the size and number of SH lesions and / or clearing the SH lesion(s) through its controlled thermal energy delivery.

[0063] This disclosure relates to treatment of Sebaceous Hyperplasia (SH) in a patient. It involves using a laser light pulse of about 1726 nm to target sebum produced by overactive sebaceous glands in a non-invasive manner to selectively treat the glands within lesions while minimizing collateral damage to surrounding tissues.

[0064] A potential benefit of laser treatment is reduction in number, size, and / or severity of SH lesions.

[0065] Definitions

[0066] Applicant specifically incorporates the entire contents of all cited references in this disclosure. Further, when an amount, concentration, or other value or parameter is given as either a range or a list of upper values and lower values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or value and any lower range limit or value, regardless of whether ranges are separately disclosed. Where a range of numerical values is recited herein, unless otherwise stated, the range is intended to include the endpoints thereof, and all integers and fractions within the range. It is not intended that the scope of the present disclosure be limited to the specific values recited when defining a range.

[0067] The indefinite articles “a” and “an”, as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one”.

[0068] The phrase “and / or”, as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Other elements may optionally be present other than the elementsspecifically identified by the “and / or” clause, whether related or unrelated to those elements specifically identified unless clearly indicated to the contrary. Thus, as a non-limiting example, a reference to “A and / or B”, when used in conjunction with open- ended language such as “comprising” can refer, in one embodiment, to A without B (optionally including elements other than B); in another embodiment, to B without A (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[0069] As used herein in the specification and in the claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when separating items in a list, “or” or “and / or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of’, or, when used in the claims, “consisting of”, will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e., “one or the other but not both”) when preceded by terms of exclusivity, “either”, “one of”, “only one of’, “exactly one of”. “Consisting essentially of”, when used in the claims, shall have its ordinary meaning as used in the field of patent law.

[0070] The term “about” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1 %, or ±0.1 % from the specified value, as such variations are appropriate to perform the disclosed methods.

[0071] The term “Adverse Event (AE)” refers to any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in clinical study subjects, device users or other persons, whether or not related to the medical device.

[0072] Adverse Event / Adverse Device Effect (AE / ADE) Relationship to Device: The relationship of an event to study device will be determined as follows:

[0073] Unrelated: The event is clearly related to other factors such as the subject’s clinical state, other therapeutic interventions or concomitant drugs administered to the subject.

[0074] Possible: The event follows a reasonable temporal sequence from the time of device administration but could have been produced by other factors such as the subject’s clinical state, other therapeutic interventions, or concomitant drugs.

[0075] Probable: The event follows a reasonable temporal sequence from the time of device administration and follows a known response pattern to the device. The event cannot be reasonably explained by other factors such as the subject’s clinical state, other therapeutic interventions, or concomitant drugs.

[0076] Definite: The event follows a reasonable temporal sequence from the time of device administration and follows a known response pattern to the device. The event cannot be reasonably explained by other factors such as the subject’s clinical state, other therapeutic interventions, or concomitant drugs AND either occurs immediately following device administration, improves on stopping device administration, or reappears on re-exposure of device administration. The classification of adverse device effects is shown in the flowchart in FIG. 2.

[0077] As used herein, “target skin area” or “target area” refers to the skin receiving the energy of a laser pulse. The target skin area may include the surface skin area illuminated by the laser pulse, as well as deeper structures beneath the surface skin that receive at least a portion of the energy from the laser pulse. As such, “target skin areas” treated by a laser pulse may refer to a volume of skin as opposed to a true area of an outer surface of the epidermis.

[0078] As used herein, “Fitzpatrick skin type” also referred as “Fitzpatrick scale” is a numerical classification scheme for human skin color and is a well-recognized tool for dermatological research.

[0079] As used herein, the terms “treat,” “treating” or “treatment” refer to an action to obtain a beneficial or desired clinical result including, but not limited to, alleviation or amelioration of one or more signs or symptoms of Sebaceous Hyperplasia. In certain embodiments, the efficacy of the treatment by a qualified individual, e.g., a dermatologist, can be evaluated using accepted assessment tools of pain and quality of life (QOL) such as, but not limited to Global Aesthetic Improvement Scale (GAIS), 11 -point (0-10) Visual Analog Pain Scale, and assessment for Adverse Events.

[0080] Dermatological systems and methods for providing a therapeutic laser treatment are disclosed in US 10,864,380 B1 , US 11 ,253,720 B2, US 11 ,400,308 B2, US 11 ,738,206 B2, US 2022 / 0168590 A1 , US 2022 / 0212026 A1 , US 2022 / 0212027 A1 , and US 2023 / 0302294 A1 ; each of which incorporated byreference herein in its entirety.

[0081] Handpieces

[0082] Large Handpiece: The treatment handpiece connects to the system console with an umbilical cable. The umbilical cable houses an optical fiber that delivers laser energy from the console to the handpiece, as well as associated electrical cables and air and water lines. The handpieces house a temperature-controlled skin-contact sapphire cooling window to provide thermal protection for the epidermis and superficial dermis and through which energy is delivered to the patient; skin-contact pressure sensors to ensure that firm and even contact with skin is maintained; and an integrated scanner for delivering an array of treatment spots. The treatment spot is a square of 3x3 mm side length. The user can select from a list of available patterns: 1x1 , 2x1 , 2x2, 3x3, 4x4, or 5x5 treatment spots. Patterrns may also be any pattern combination that could be made from a 5X5 grid, for example, a 1x3, 2x4, 3x2.

[0083] Universal Handpiece: The treatment handpiece connects to the system console with an umbilical cable. The umbilical cable houses an optical fiber that delivers laser energy from the console to the handpiece, as well as associated electrical cables and air and water lines. The handpieces house a temperature-controlled skin-contact sapphire cooling window to provide thermal protection for the epidermis and superficial dermis and through which energy is delivered to the patient; skin-contact pressure sensors to ensure that firm and even contact with skin is maintained; and an integrated scanner for delivering an array of treatment spots. The treatment spot is a circle with a diameter of about 3 mm. Another option is to use a 7-spot hexagonal pattern or a single central treatment spot. Another option is to use a circular treatment spot from about 4 mm to about 5 mm diameter. Thus, the spot size may be a circular spot from about 3 mm to about 6 mm.

[0084] Fluence ranges and pulses (and sub-pulses): The laser pulse may be delivered in one pulse, two sub-pulses, three sub-pulses, four sub-pulses, or five sub-pulses. For example, for multi-pulse (more than one pulse) the fluence would depend on the sub-pulse spacing, with spacing of about 500 ms to about 2000 ms. For example, a sub-pulse spacing of about 200 ms may provide effective cooling of the epidermis which is beneficial. Depending on the size of the lesion, the total fluence delivered in the two sub-pulses might need to be increased, from a one pulse scnerio. For a pulse spacing of 500 ms while for treating larger SH lesions the totalfluence may not need to increase.

[0085] The 1726 laser system is capable is pre-cooling and post-cooling the skin pre and post treatment. The skin, when treating SH may be pre-cooled from 1 second up to 20 seconds. The skin, when treating SH may be pre-cooled from 1 second up to 5 seconds, or the skin, when treating SH may be pre-cooled from 1 second up to 2 seconds. The skin may be post-cooled, after laser firing, from 1 to 20 seconds.Post- cooling may also be done from 1 to 5 seconds.

[0086] The 1726 Laser System

[0087] One example of the 1726 nm laser system has the about 1726 nm energy and when coupled with skin cooling selectively heats the sebum in the sebaceous gland in the mid to upper dermis while simultaneously protecting the epidermis and superficial dermis, resulting in controlled thermal injury of the glands and thus the reduction or elimination of sebum production. The 1726 laser system comprises one or more of the following components:

[0088] Console: The console may contain one or more of the following, the diode laser and associated beam delivery optics, laser and electronics power supplies, control electronics, cooling system, mains-power key-switch, emergency off switch, and touch screen user interface.

[0089] Umbilical cable: The umbilical cable may contain one or more of the following an optical fiber that delivers laser energy from the console to the treatment handpiece and associated electrical cables and water lines.

[0090] Treatment handpieces: The treatment handpieces have one or more of the following a) an integrated scanner for delivering treatment spot(s) in an operator selected pattern, b) a temperature-controlled skin-contact cooling window to provide thermal protection for the epidermis and superficial dermis and through which energy is delivered to the patient, and c) (when the system is in “Ready” mode with the footswitch depressed) skin-contact pressure sensors to activate laser energy delivery.

[0091] Footswitch: The footswitch enables laser activation by the skin-contact pressure sensors when the device is in “Ready” mode. As an alternatve to the footswitch, the device may have a hand switch or a switch on the device, or handpiece or a separate connected switch that can be used by the provider or another person in the room.

[0092] Remote interlock plug: The remote interlock plug, when wired to an externaldoor switch, shuts down the system power (returns the device to “Standby” Mode) if the treatment room door is opened or plug is removed.

[0093] Universal handpiece: may have 3 mm round spot (0.07 cm2); 10 mm 7-spot hexagonal array; 5 mm x 5 mm 4-spot square array, and other spot sizes are arrays disclosed herein.

[0094] Large handpiece: may have 3 mm square spot (0.09 cm2); 6 mm x 3 mm 2- spot array; 6 mm x 6 mm 4-spot array; 9 mm x 9 mm 9-spot array; 12 mm x 12 mm 16-spot array; 15 mm x 15 mm 25-spot square array, and other spot sizes discosed herein.

[0095] Single Spot handpiece: 3 mm round spot, from about 1 mm to about 10 mm spot size.

[0096] Table 1 describes the parameters of certain embodiments of the universal and large handpieces.

[0097] Table 1 : Specifications of the universal handpiece (HP) and large handpiece (HP).EXAMPLES

[0098] Example 1

[0099] Therapeutic Laser. The method of treating Sebaceous Hyperplasia (SH) disclosed herein employs a therapeutic laser having a wavelength of about 1726 nm to irradiate a sebum or a sebaceous gland with a spot of a laser pulse.

[0100] The laser system used herein is Cutera® 1726 nm laser system, also referred to as “1726 Laser System”. The laser system is manufactured by Cutera, Inc, is indicated for the long-term treatment of mild to severe inflammatory acne vulgaris (K230660). This infrared diode laser device uses pulsed laser energy at a wavelength of 1726 nm. Similar to other well-established infrared laser devices, the treatment spot size, beam characteristics, tissue absorption and scattering coefficients at the output wavelength define the tissue penetration depth of the delivered energy. When combined with pre, parallel (during energy delivery), and post cooling of epidermal and superficial dermal structures, selective heating of dermal tissue at different depths is enabled.

[0101] IThe pre-cooling time to be sufficient to effectively cool the superficial structure of the skin, namely the epidermis and superficial dermis, but it is not recommended to be so long as to cause the sebaceous gland(s) to be cooled. TSafety algorithms may be contained in the 1726 Laser System to ensure that the appropriate amount of cooling is applied to the skin before, during and after the laser pulse is administered.

[0102] The 1726 nm laser energy when coupled with skin cooling selectively heats the sebum in the sebaceous gland in the mid to upper dermis while simultaneously protecting the epidermis and superficial dermis, resulting in controlled thermal injury of the glands and thus the reduction or elimination of sebum production.

[0103] The 1726 Laser System may comprise of one ore more of the following components:

[0104] Console: The console houses the diode laser and associated beam delivery optics, laser and electronics power supplies, control electronics, cooling system, mains-power key-switch, emergency off switch, and touch screen user interface.

[0105] Umbilical cable: The umbilical cable houses an optical fiber that delivers laser energy from the console to the treatment handpiece and associated electrical cables and water lines.

[0106] Treatment handpiece: The treatment handpiece has a) an integrated scanner for delivering treatment spot(s) in an operator selected pattern, b) a temperature- controlled skin-contact cooling window to provide thermal protection for the epidermis and superficial dermis and through which energy is delivered to the patient, and c) (when the system is in “Ready” mode with the footswitch depressed) skin-contact pressure sensors to activate laser energy delivery.

[0107] The device specifications of 1726 nm Laser System is given in Table 2.

[0108] Table 2: 1726 nm Laser Specifications.

[0109] During treatment, the operator interacts with the console via the touch-screen user interface which presents the controls used by the Investigator (or qualified designee) to monitor and set the system status (including “Off”, “Standby” and Ready” modes) and treatment parameters. The operator adjustable treatment parameters include the treatment fluence, spot pattern, and the skin contact cooling window temperature. The touchscreen user interface also presents other displays and indicators to ensure safe and accurate operation.

[0110] The pulse duration of a single or double pulse may be up to 500 ms; or from about 1 ms to about 500 ms; or from about 5 ms to about 50 ms; or from about 10 ms to about 400 ms.

[0111] After the device is in “Ready” mode and the footswitch is depressed, treatment is applied using a stamping method, meaning that the temperature- controlled treatment window is pressed against the skin with sufficient firm and even pressure to initiate cooling prior to, during, and post laser energy application.Following a 1 - 20 second pre-cooling delay, energy delivery to the treatment spots (in the selected spot pattern and pulse mode), and a 1 - 10 second post-cooling delay, the system generates an audible signal to the user to lift the hand piece and move to the next treatment area and the process is repeated as shown in the flow chart in FIG. 1.

[0112] It is important for the pre-cooling time to be sufficient to effectively cool the superficial structure of the skin, namely the epidermis and superficial dermis, but not so long for the sebaceous glands to be cooled. Cooling prior to the pulse acts as an anesthetic and protects the epidermis and superficial dermis from the irradiation of the laser pulse. Cooling during the energy delivery (parallel cooling) further protects the epidermis and the superficial dermis. Cooling after the pulse prevents thermal injury to the epidermis and superficial dermis from the thermal blooming (conducted energy) that diffuses from the sebaceous glands.

[0113] Potential Risks: Possible risks or ADEs associated with 1726nm laser treatment or similar laser devices / procedures are listed as follows: edema, erythema, heat sensation during treatment, pain or discomfort during treatment, skin dryness, textural changes, blistering, scabbing / crusting, hyperpigmentation, hypopigmentation, infection, oozing (serum or plasma), pruritus, scarring, transient acne flareups, harmful eye exposure to light energy, altered hair growth in treatment area, bleeding, small papules, burn, and erosions.

[0114] Possible risks also include unintended injury to subject, user, or others due to user error (e.g., unintentional treatment to non-target location) or equipment problem (e.g., device malfunction). Subjects will be asked to wear eye protection during the laser procedure to prevent eye damage.

[0115] Example 2

[0116] Study Design. The comprehensive evaluation of the safety of the 1726 Laser System for the treatment of Sebaceous Hyperplasia (SH) is described in this study design.

[0117] The study is a prospective, open label, single arm, non-significant risk study. Up to 30 subjects, age 18 to 80 years, with a minimum of one SH lesion at baseline. Enrolled subjects with qualifying SH lesion will receive one (1 ) lesion specific 1726 laser treatment.

[0118] Follow-up visits will occur at approximately 7 (+3 / -2) days post-treatment (via phone) and at 4 (±1 ) weeks and 8 (±1 ) weeks post treatment for an on-site evaluation.

[0119] At 4-weeks and 8-weeks post the initial treatment, the treated SH lesions will be assessed and determine if an additional lesion-specific treatment with the 1726 Laser System is needed, with a maximum of three treatments per SH lesion possible. In case of more than a single treatment, the subject will be followed at anadditional 7 days, 4-weeks and 8-weeks post their treatment. Subjects may also be followed up at 12- and / or 26-weeks post final treatment.

[0120] Standardized digital photographs and dermatoscope images may be taken of each subject’s treatment and control areas at all visits.

[0121] Subjects will use an approved mild cleanser and daily sunscreen on the face of SPF 30 or higher, and will be asked to practice strict, diligent prevention of sun exposure.F01221 Example s

[0123] Study Duration. Subjects enrolled in this study will participate for up to approximately 4 months and complete up to 7 visits.1 screening / baseline visit;Up to 2 treatment visits with a 4 (± 1 ) week interval;Up to 2 follow-up visits via phone at approximately 7 (+3 / -2) days post each treatment visit;Up to 4 on-site follow-up visits at 4 (± 1), 8 (± 1 ) , 12 (± 2), 26 (± 3)weeks post final treatment.

[0124] Example 4

[0125] Study Outcome Measures.

[0126] Primary Safety Endpoint: The primary outcome measure is to evaluate the incidence and severity of all reported adverse events throughout the study duration, including subject pain level during treatment as rated by the subject using the 11- point (0-10) Visual Analog Pain Scale that is shown in FIG. 3.

[0127] Exploratory Endpoints: The exploratory endpoints that may be evaluated are including, but are not limited to:

[0128] GAIS Improvement of the treated SH lesions at 4-, 8-, 12 and / or 26-weeks post final treatment per lesion as measured by blinded expert evaluators.

[0129] GAIS score may be assessed by at least one independent evaluator, blinded to treatment assignment, who will classify the response for each lesion based on photographs taken at baseline, 4-, 8-, 12- and / or 26-weeks post last treatment. The observer(s) will assign a score based on the 5-level GAIS scale.

[0130] Each SH lesion will be classified as a Responder if 2 of the 3 blinded evaluators assign a score of 4 or 5, and as a Non-Responder if 2 of the 3 blinded evaluators assign a score of 1 , 2, or 3. The timing of the evaluation of this endpoint is lesion specific as some lesions may not require a second treatment.

[0131] Percent reduction from baseline to 4-, 8-, 12- and / or 26-weeks post final treatment in quantity of SH lesions per subject.

[0132] Assessment of subject reported treatment satisfaction, including quality of life measures, at baseline, 4-, 8-, 12- and / or 26-weeks post final treatment.

[0133] Analysis Sets: The primary endpoint / safety analysis set will include all subjects enrolled in the study who complete at least one laser treatment session. The exploratory efficacy analysis set will include all subjects who complete baseline, receive at least one laser treatment session and complete at least one follow-up visit.

[0134] Example 5

[0135] Safety Assessments.

[0136] Incidence and Severity of Adverse Events: Following the first laser treatment, adverse events (AEs) / adverse device effects (ADEs) will be assessed posttreatment and at each subsequent subject visit.

[0137] Treatment-related Discomfort: Immediately post treatment of each lesion, subjects will be asked to rate the average amount of discomfort experienced during laser treatment using the Pain Rating Scale that is shown in FIG. 3.

[0138] Exploratory Efficacy Endpoints: The exploratory endpoints may include, but are not limited to:

[0139] Global Aesthetic Improvement Scale: The Global Aesthetic Improvement Scale (GAIS) score may be assessed by at least one independent evaluator, blinded to treatment assignment, who will classify the response for each lesion based on photographs taken at baseline, 4-, 8-, 12 and / or 26-weeks post final treatment. A score based on the 5-level GAIS as shown in Table 3 will be assigned by the observers.

[0140] The GAIS score may be assessed by at least one independent evaluator, blinded to treatment assignment, who will classify the response for each lesion based on photographs taken at baseline and 4-, 8-, 12 and / or 26-weeks post last treatment. The observers will assign a score based on the 5-level Global Aesthetic Improvement Scale listed in Table 3.

[0141] Table 3 : Global Aesthetic Improvement Scale (GAIS).

[0142] Before each evaluation, close-up photographs from baseline, 4-, 8-, 12- and / or 26-week post-treatment follow-up will be randomly presented with labels concealed, ensuring the assessors remain blinded to the assessment time points. During each assessment, the assessors will review close-up photographs of individual SH lesions in random order and determine any changes in appearance. Each assessor will assign a GAIS score to rate the change in appearance of each SH lesion.

[0143] Each SH lesion will be classified as a Responder if 2 of the 3 blinded independent evaluators assign a score of 4 or 5, and as a Non-Responder if 2 of the 3 blinded evaluators assign a score of 1 , 2, or 3. The timing of the evaluation of this endpoint is lesion specific as some lesions may not require a second treatment.

[0144] If the blinded evaluator determines an SH lesion as Not Evaluable (NE), it will be also be excluded from analysis.

[0145] Reduction in Number of SH Lesions: The percentage reduction in the quantity of SH lesions per subject from baseline to 4-, 8-, 12 and / or 26-weeks post final treatment.

[0146] Example 6

[0147] Study Population. Up to 30 subjects, ages 18 to 80, with Fitzpatrick Skin Type l-VI presenting with at least one qualifying SH lesion will be included.

[0148] Inclusion Criteria: To be included in the study, subjects must meet all the following Inclusion Criteria:

[0149] 1. Subjects is 18-80 years of age (inclusive) and Fitzpatrick Skin Types l-VL

[0150] 2. Subject has at least one clinically diagnosed SH lesion on their face, excluding the nose and within the orbital rim, as determined by the PI.

[0151] 3. Subject is willing to have SH lesions treated and understands that their lesion(s) may undergo one additional treatment session at the discretion of the investigator at a subsequent visit.

[0152] 4. Subject must be able to read, speak, and understand English and sign the Informed Consent Form.

[0153] 5. Subject is willing and able to adhere to the treatment and follow-up schedule and pre / post-treatment care instructions.

[0154] 6. Subject is willing to have photographs taken of the target area and agrees to the use of photographs for presentation, educational, or marketing purposes.

[0155] 7. Subject agrees to refrain from using all other lesion removal products or treatments (e.g., retinols, retinoids, exfoliating products) to the treated SH lesions or any new SH lesions during the study period.

[0156] 8. Subject is willing to have very limited sun exposure (including avoiding tanning booths, sun lamps, sunbathing) and use an Investigator approved sunblock or sunscreen of SPF 30 or higher on the treatment area every day for the duration of the study, including the follow-up period.

[0157] 9. Female subjects of child-bearing age are willing to use a medically acceptable form of birth control at least 90 days prior to enrollment and during the entire course of the study.

[0158] 10. Subject agrees to not undergo any other procedure(s) or add any new treatment modalities in the target area during the study.

[0159] Exclusion Criteria: Subjects will be excluded from the study if they meet any of the following Exclusion Criteria:

[0160] 1. Subject has participated in a clinical trial treating the target area within 30 days prior to study participation.

[0161] 2. Subject has received injections of botulinum toxin, collagen, hyaluronic acid filler, or dermal fillers in the target area within 30 days prior to study participation.

[0162] 3. Subject has undergone prior treatments for any reason to the target area within 30 days of study participation, such as chemical peels, dermabrasion, microneedling, radiofrequency treatment, laser or light-based procedures, cryodestruction or chemodestruction, intralesional steroids, photodynamic therapy, or surgery.

[0163] 4. Subject has used topical lesion removal products (e.g., retinols, retinoids, exfoliating products) within 30 days of study participation and / or systemic use of retinoid, such as isotretinoin, within 90 days of study participation.[0164J5. Subject has history of diagnosed immunosuppression / immune deficiency disorders or currently using prednisone or anti-rejection medications.

[0165] 6. Subject has history of malignant tumors in the target area.

[0166] 7. Subject has history of suffering from diagnosed coagulation disorders or taking prescription anticoagulation medications. Low dose (81 mg) aspirin is permitted.

[0167] 8. Subject has history of diagnosed connective tissue disease, such as systemic lupus erythematosus or scleroderma.

[0168] 9. Subject has personal history or Family History of Muir-Torre Syndrome or with a known history of multiple family members (including parents, grandparents, siblings, or children) with colon cancer at discretion of Investigator.

[0169] 10. Subject has history of Basal Cell Nevus Syndrome.

[0170] 11. Subject has history of disease stimulated by heat, such as recurrent herpes simplex and / or herpes zoster (shingles) in the target area, unless treatment is conducted following a prophylactic regimen.

[0171] 12. Subject has history of radiation to the target area, currently undergoing treatment for skin cancer in the target area or undergoing chemotherapy for the treatment of any cancer.

[0172] 13. Subject has any use of medication(s) that is known to increase sensitivity to light according to Investigator’s discretion.

[0173] 14. Subject is prone to developing hypertrophic scars or to be keloid producer.

[0174] 15. Subject has presence of any skin condition in the target area (e.g. eczema, psoriasis, dermatitis, rash, papulo-pustular rosacea, infection, open wounds, irregular or atypical moles, questionable pigmented lesions) that would interfere with the diagnosis or assessment of SH.

[0175] 16. Subject has excessive hair in the target area (e.g. beards, sideburns, moustaches, scalp, etc.) that would interfere with diagnosis or assessment of SH in the target area (okay if shaved).

[0176] 17. Subject is excessively tanned on the target area or unable / unlikely to refrain from tanning on the target area during the study.

[0177] 18. Subject has tattoos or permanent makeup on the target area.

[0178] 19. Subject has a metal or electronic implant under the skin in the target area.

[0179] 20. Subject is pregnant and / or breastfeeding or planning to become pregnant during the study.

[0180] 21. As per the Investigator’s discretion, any physical, mental, or medical condition that might make it unsafe for the subject to participate in this study or might interfere with subject’s participation in the full study protocol.

[0181] Example 7

[0182] Screening Visit Procedures. The following procedures will occur.

[0183] 1. Informed Consent.

[0184] 2. Subject is assigned a Subject ID.

[0185] 3. Assess and document study eligibility (inclusion / exclusion) criteria.

[0186] 4. Collect and document demographic information.

[0187] 5. Assess and document medical history.

[0188] 6. Assess and document concomitant prescription or over-the-counter medications (including vitamins / herbs / supplements) currently used or used prior to the screening visit.

[0189] 7. Assess and document concomitant skincare products currently used in the treatment area.

[0190] 8. Have women of childbearing potential (WOCBP) complete a urine pregnancy test (UPT).

[0191] 9. Record date of last menstrual cycle for women of childbearing potential (WOCBP).

[0192] 10. Cleanse subject’s face with an Investigator / Sponsor approved mild cleanser to remove all cosmetics, make-up and lotions.

[0193] 11. Board Certified Investigator will assess, and designate SH lesions intended for treatment. The treatment area may be shaved if necessary.

[0194] 12. Trained staff will take standardized digital photographs of the subject’s face. These photographs will be used to perform GAIS assessments.

[0195] 13. Trained staff will take dermatoscope images of subject’s SH lesions.

[0196] 14. The before and after treatment instructions will be explained and provided to the subject.

[0197] After obtaining informed consent and confirming that the subject meets all other eligibility criteria for enrollment into the study, the Investigator abd / or expert evaluator will clinically assess the subject's baseline photographs.

[0198] Example 8

[0199] Treatment Visit Procedures. All subjects will have up to three (3) treatment visits at a 4 (±1 week) interval.

[0200] a) Pre-Treatment Procedures

[0201] The following procedures will occur prior to beginning the treatment:

[0202] 1. Confirm subject continues to meet the study eligibility criteria.

[0203] 2. Assess and record any changes to subject’s medical history since the previous study visit. This data will only be collected prior to the delivery of the first treatment.

[0204] 3. Assess and record any additions, changes and / or deletions in prescription and nonprescription concomitant medications (including vitamins / herbs / supplements) since the previous study visit.

[0205] 4. Assess and record any additions, changes and / or deletions in concomitant skincare products used in the treatment area since the previous study visit.

[0206] 5. Have WOCBP complete a UPT.

[0207] 6. Record date of last menstrual cycle for WOCBP.

[0208] 7. At treatment visit 1 only, the subject will complete and return the Baseline Questionnaire prior to treatment.

[0209] 8. If applicable, at treatment visit 2 and 3 only, assess for any new adverse events / adverse device effects (AEs / ADEs) or changes to previously recorded AEs / ADEs since the prior treatment.

[0210] 9. If applicable, at treatment visit 2 and 3, trained staff will take standardized digital photographs of the subject’s face.

[0211] 10. If applicable, at treatment visit 2 and 3, trained staff will take dermatoscope images of subject’s SH lesions.

[0212] 11. Cleanse subject’s treatment area with an Investigator / Sponsor approved cleanser to remove all cosmetics, make-up and lotions.

[0213] 12. Investigator (or qualified designee) will review and identify the SH lesions intended for treatment. The treatment area may be shaved if necessary.

[0214] b) Treatment Procedures

[0215] Subjects will receive treatment to the designated area with the 1726 Laser System as follows:

[0216] 1. The subject and the staff in the laser treatment area must wear appropriate laser protective eyewear with an optical density sufficient to protect from the 1726 nm treatment wavelength.

[0217] 2. The subject should be lying down and comfortable while undergoing the laser treatment and the operator (Investigator or qualified designee) should have easy access to both the device and the subject’s treatment area.

[0218] 3. The study staff will cleanse the subject’s full face with an alcohol swab, acetone or other Investigator / Sponsor approved degreasing agent.

[0219] 4. The operator (Investigator or qualified designee) will prepare the subject and conduct treatments using the 1726 Laser System and according to the operator manual. All operator adjustable laser treatment settings will be selected at Investigator’s (or qualified designee’s) discretion.

[0220] 5. The laser serial number, treatment settings used, and time of treatment will be recorded. The treatment may be video recorded.

[0221] 6. Immediately post treatment to each lesion, the subject will be asked to rate the level of discomfort felt during the treatment using the 11 -point VAS Pain Rating Scale as shown in FIG. 3.

[0222] 7. The Investigator (or qualified designee) will assess the post-treatment adverse device effects (ADEs).

[0223] 8. Trained staff may take post treatment photographs and / or dermatoscope images of the subject’s SH lesions.

[0224] 9. Study staff will remind the subject of after-treatment care instructions.

[0225] 10. The device shall be cleaned / disinfected between uses according to the instructions specified in the operator manual.

[0226] c) Follow-up visit procedures.

[0227] The follow-up visit will occur at approximately 7 (+3Z-2) days post treatment via phone, and on-site at 4 (+1 ) weeks and 8 (+1 ) weeks post final treatment.

[0228] The following procedures will be performed at all follow-up visits:

[0229] 1. Confirm subject continues to meet the study eligibility criteria.

[0230] 2. Assess and record any additions, changes and / or deletions in prescription and nonprescription concomitant medications (including vitamins / herbs) since the previous study visit.

[0231] 3. Assess and record any additions, changes and / or deletions in skincare products used in the treatment area since the previous study visit.

[0232] 4. Assess for any new AEs / ADEs or changes to previously recorded AEs / ADEs.

[0233] 5. Record date of last menstrual cycle for WOCBP.

[0234] 6. Study staff will remind the subject of after-treatment care instructions.

[0235] The following procedures will be performed at the 4 and 8-weeks post final treatment follow-up visits only:

[0236] 7. Cleanse subject’s face with a mild cleanser to remove all cosmetics, makeup and lotions.

[0237] 8. Trained staff will take standardized digital photographs of the subject’s face. These photographs will be used to perform GAIS assessments.

[0238] 9. Trained staff will take dermatoscope images of subject’s SH lesions.

[0239] 10. At the 8-weeks post final treatment follow-up visit, a UPT will be performed for WOCBP.

[0240] 11. Subject will complete and return the Follow-Up Subject Questionnaire.

[0241] The 7-day post treatment follow-up visits will occur via phone unless it is determined by the Investigator or designated study staff that it is in the best interest of the subject to conduct the 7-day follow-up visit on-site or it is more convenient for both the subject and study staff to conduct the visit on-site. If the 7-day post treatment follow-up visit occurs on-site, photographs and / or dermatoscope images may be taken.

[0242] d) Unscheduled Visits / Procedures.

[0243] It is at the discretion of the Investigator (or qualified designee) to ask the subject to return to the study site prior to any regular scheduled visit or on a more frequent basis if for example the subject experienced an adverse event, session for photography, or it is in the best interest of the subject. At any time throughout the study, if the subject experiences an adverse event, the subject may be asked to provide photographs for the Investigator to assess. If subject withdraws or exits the study early, the subject may be asked to return to the site for a final assessment / early termination visit.

[0244] Example 9

[0245] Treatment of SH Lesion. FIG. 4 shows an example of a treatment of an SH lesion before (FIG. 4A) and after treatment (FIG. 4B). The median improvement score was 2 on a 3-point scale. After treatment, the gland density is significantly increased; the glands have longer thermal relaxation times due to increased density; the glands are more superficial. Treatment was done with fluences in 24 J / cm2to 30 J / cm2range (short pulse). This is shown an example of a successful treatment withno sign of indentation or scarring. Also, longer, more energetic pulse with reduced cooling may provide safer, less painful treatment.

[0246] Example 10

[0247] Results of 4 Patient Study with 1726 Laser System using UniversalHandpiece. N=4 subjects completed treatment session. A total of n=7 SH lesions were treated. The settings of 1726 Laser was Universal HP, single-spot. Table 4 shows the results of the 4 subject study.

[0248] Table 4: Results from 4 Patient Study with 1726 Laser System using Universal Handpiece.[02491 Example 11

[0250] Results of 2 Patient Study with 1726 Laser System using LargeHandpiece. N=2 subjects completed treatment session. A total of n=5 SH lesions were treated. The settings of 1726 Laser was Large HP, 4-spot array; Fluence: 30 J / cm2Sapphire Cooling Window: 5° C. Table 5 shows the results of the 2 subject study.

[0251] Table 5: Results from 2 Patient Study with 1726 Laser System using Large Handpiece.

Claims

CLAIMSWhat is claimed is:1 . A method of treating Sebaceous Hyperplasia (SH) in a patient comprising: irradiating a sebum or a sebaceous gland that is a SH lesion with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, and wherein the treatment resulted in a reduction of the size or clearance of SH lesions.

2. The method of claim 1 , wherein the patient has at least two SH lesions.

3. The method of claim 1 , wherein the patient received up to three treatments per SH lesion.

4. The method of claim 1 , wherein the treatment resulted in 4 or 5 on the Global Aesthetic Improvement Scale (GAIS).

5. The method of claim 1 , wherein the treatment resulted in a reduction in lesion size from 2 mm to 2.5 mm.

6. The method of claim 1 , wherein the treatment resulted in clearance of the lesion.

7. The method of claim 1 , wherein the sebaceous gland density is significantly increased after the treatment.

8. The method of claim 1 , wherein the sebaceous glands are more superficial.

9. The method of claim 1 , wherein the treatment was done with fluences in 24 J / cm2to 30 J / cm2range or 5 J / cm2to 30 J / cm2range.

10. The method of claim 1 , wherein the skin shows no sign of indentation or scarring after the treatment.

11. The method of claim 1 , wherein the treatment is done with longer and more energetic pulse with cooling from about 1 degree C to about 5 degress C.

12. The method of claim 1 , wherein the spot of the therapeutic laser is delivered with a single spot pattern, a two spot pattern, a four spot pattern or any pattern that can be made from a five by five grid.

13. The method of claim 1 , wherein the power of the therapeutic laser pulse delivered is selected from about 5 W to about 90 W of power, from about 10 W to about 40 W of power or from about 20 W to about 50 W of power.

14. The method of claim 1 , wherein the SH lesion or lesions are treated with a single or double pulse of the therapeutic laser.

15. The method of claim 1 , wherein the patient’s entire face is treated with the therapeutic laser.

16. The method of claim 1 , wherein the duration of the therapeutic pulse is selected from a single or double pulse of up to 500 ms, from about 1 ms to about 500 ms, from about 5 ms to about 50 ms, or from about 10 ms to about 400 ms.

17. The method of claim 1 , wherein the spot size of the therapeutic laser pulse is from about 3 mm2to about 9 mm2or from about 3 mm2to about 36 mm2or from about 0.08 mm2to about 9 mm2.

18. The method of claim 17, wherein the spot is circular or square in shape.

19. The method of claim 1 , wherein the power of the therapeutic laser pulse delivered is from 5 W and 90 W of power.

20. The method of claim 1 , wherein the treatment applies to Fitzpatrick skin types l-VI.

21. The method of claim 1 , wherein the patient is at least 12 years of age or older.

22. The method of claim 1 , wherein the patient is aged between 12 and 80 years.

23. A method of treating Sebaceous Hyperplasia (SH) in a patient comprising: irradiating a sebaceous hyperplasia lesion with a spot of a therapeutic laser pulse having a wavelength of about 1726 nm, and irradiating the sebaceous hyperplasia lesion a second time within 8 weeks, and wherein the treatment resulted in a reduction of the size or clearance of the SH lesion.

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