Patent Application
20210361970
This application claims priority of European Patent Application No. 20176304.2 filed May 25, 2020, which is hereby incorporated herein by reference.
The present invention relates to an applicator as well as methods for ameliorating alopecia, for improving the quality, color and/or density of hair, and/or for improving a to condition of a scalp of a person by laser light.
Alopecia is very frequent. Particularly, androgenic alopecia affects more than 50% of men and 25% of women over 50 years of age. In men, hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic “M” shape, also known as male-pattern baldness. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness. The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner all over the head, but the hairline does not recede. In women, androgenic alopecia rarely leads to total baldness, but to decreased hair density and thickness. Still, for both men and women, it has a major impact on self-esteem and quality of life.
Androgenic alopecia is a multifactorial process, involving genetic, hormonal and local inflammatory factors. Local fibrosis and degenerative vascular changes are often seen in scalp histologies of persons having androgenic alopecia.
Hair transplantation remains the most effective response to alopecia but comes at considerable cost. More importantly, it is also invasive.
Common pharmaceutical therapies include oral finasteride, an inhibitor of the 5-alpha reductase enzyme, blocking the conversion of testosterone into its more potent form dihydrotestosterone, which is among the determining factors for androgenetic hair loss. Oral finasteride is available for men only. Other common pharmaceutical therapies rely on oral or topical minoxidil, which is assumed to work by improving the vascularization of the scalp, although its exact mechanism of action remains largely unclear.
It is important to recognize that scalp problems are often at the root of a person's hair concerns. Therefore, improving the condition of the scalp is also of importance. Typical scalp condition related hair concerns include dandruff, and dry and itchy scalp.
Alternative approaches to ameliorating alopecia and stimulating hair growth are based on topical administration of growth factors or natural ointments or on injection of growth factors or platelet rich plasma (PRP). Stem cell therapies are also viable. The common denominator of all these approaches is stimulation of regenerative processes in existing hair follicles and the induction of hair neogenesis.
This effect may also be obtained employing energy-based devices, lasers in particular. Mainly, laser stimulation of hair growth as known in the art uses low-energy lasers of various wavelengths, stimulating cellular metabolism and hence tissue turnover and regeneration (so-called low-level light therapy, or LLLT for short). But it is generally also viable to use higher energy, which may be non-ablative or also ablative, e.g., to drill microholes into tissue, causing mechanical damage resulting in wound-repair induced tissue regeneration (fractional ablative stimulation).
Approaches for ameliorating alopecia usually envisage stimulation of hair growth (e.g. density and/or thickness) in the beginning stages of the condition, when there may still be a substantial amount of hair present. But delivering laser light to skin covered with hair—in particular the scalp—is a challenge. Laser light will be absorbed, reflected and/or scattered by the hair at least partially before reaching the skin. Next to stymieing effectiveness, this also makes determination of accurate, reproducible protocols impossible.
Of course, the most basic solution to this problem is to manually part the hair before applying laser light spot-by spot. This is rather undesirable, though, as it is heavily user-dependent and very time-consuming.
A more elaborate solution known in the art is to arrange laser diodes in rows or other patterns on a comb-like device that parts the hair and thus enables laser light delivery directly to the skin. However, due to the necessary restrictions in size of the laser diodes, only low-energy laser light may be utilized in such devices, restricting this solution to the LLLT domain. Moreover, even with these devices it remains difficult to cover the whole scalp—or any target area more generally—equally.
Therefore, there is a need for an improved approach to ameliorating alopecia, improving quality, color and/or density of hair, and/or improving a condition of a scalp by laser light.
It is to be noted that in the following the expression “ameliorating alopecia” is always meant to additionally also encompass improving quality, color and/or density of hair, and/or improving a condition of a scalp.
The above need is at least partly met by an applicator according to claim 1.
In a first aspect, the present invention relates to an applicator for ameliorating alopecia, for improving quality, color and/or density of hair, and/or for improving a condition of a scalp of a person by laser light that comprises means for splitting at least one laser beam into at least two partial laser beams as well as at least two output means, each adapted to apply at least one of the at least two partial laser beams to the person, wherein the at least two output means are adapted such that hair can be accommodated at least partly in between them.
By splitting at least one laser beam into at least two partial laser beams which are then applied via a suitable number of output means that may accommodate hair at least partly in between them, applicators according to the present invention allow to deliver laser light, in particular high-energy laser light, with power densities of individual laser pulses delivered to tissue surface higher than 10 W/cm2, preferably higher than 100 W/cm2 and most preferably higher than 1000 W/cm2 (the power density may refer to a peak density of a pulse or an average density of a pulse sequence) directly to a tissue surface of a person having alopecia, whether or not the tissue surface is covered with hair, in an even and seamless manner. However, it is to be appreciated that the invention can also be used in combination with treatments consisting of delivering low power laser radiation, with average power densities over the treatment duration of 0.5 s to 5 s being below 3 W/cm2, preferably below 0.5 W/cm2.
By providing the at least two output means in a manner such that they can accommodate hair in between them, they may displace hair, e.g., guiding it through voids in between the output means, rather than moving or hovering atop the hair when the applicator is moved along, e.g., the scalp of a person. In a way, the output means may thus function like the teeth of a comb or a brush. As such, the present invention avoids a manual parting of the hair, dispensing with cumbersome and time-consuming user intervention. Consequently, the present invention also avoids the spot-by-spot application of laser light known from the state of the art. In effect, this enables good reproducibility as well as control of parameters and results.
At the same time, splitting at least one laser beam into at least two partial laser beams allows to use high-energy lasers for ameliorating alopecia, for improving quality (e.g., thickness), color and/or density of hair, and/or for improving a condition of a scalp. More specifically, the present invention circumvents the need for a plurality of laser light sources, e.g., one per (partial) laser beam, that accordingly need to be limited in size and hence also in power to be arranged in a compact pattern. Instead, a high energy laser beam may be received from an external source, for example, and then split into partial laser beams. As such, the present invention allows to exploit the desirable effects high-energy laser light has been found to have for reversal of hair loss as well as for formation of new hair follicles. The limited tissue response that may be achieved by LLLT thus may be overcome and more effective triggering of keratinocytes may be achieved that may be essential for the activation of signaling pathways that lead to reversal of hair loss as well as to formation of new hair follicles.
In an example, the at least two output means may be specifically adapted to be placed on a tissue surface of the person, thereby augmenting the hair-displacing effect of the output means. This may maximize reproducibility and control of parameters as well as results as it ensures that no hair is present between the output means and the tissue surface of the person.
In an example, at least one of the output means may comprise at least one of a spacer tube, a hollow waveguide and/or an optical fiber. Spacer tubes, hollow waveguides and optical fibers all allow delivering a (partial) laser beam along their length, while shielding the (partial) laser beam from interaction—i.e., absorption, reflection and/or scattering—with hair of the person on which the applicator is used. More specifically, Spacer tubes, hollow waveguides and optical fibers may function akin to teeth of a comb or a brush while allowing to guide (partial) laser beams to their respective ends. Advantageously, spacer tubes, hollow waveguides and optical fibers do not induce any losses in the (partial) laser beams that they guide and shield, thereby further enhancing reproducibility and control of parameters as well as results.
Additionally or alternatively, at least one of the output means may comprise at least one of an output lens and/or a window that is transparent with respect to the at least one laser beam. By providing at least one of the output means with a window, an inner of the applicator may be isolated from the environment, in particular, e.g., from the person and his/her scalp and/or other tissue surface, while still allowing to output the (partial) laser beam(s), preferably directly to the scalp and/or tissue surface. On the one hand, this is desirable for hygiene reasons. On the other hand, this may avoid damage to the applicator, increasing its longevity. Using an output lens may entail similar advantages, but in addition output lenses allow to further control the (partial) laser beam(s). For example, the output lens may (re)focus the (partial) laser beam, or it may adjust its diameter. In particular if the output means comprise spacer tubes, such output lenses may be used to focus the respective partial laser beam within the spacer and to defocus it again when it leaves the spacer tube. Such an output lens may also be adapted to collimate the partial laser beam applied by the output means. All of this may enhance effectiveness, but also reproducibility and control.
In an example, at least one of the output means may be flexible and/or elastic. On the one hand, this may increase comfort for the person on which the applicator is used, especially if the output means are adapted to be placed on a tissue surface of the person. On the other hand, if the output means are flexible and/or elastic, they may better adapt to the target tissue surface, hence increasing effectiveness, reproducibility and control over the (partial) laser beam application even further.
In another example, at least one, more than one but not all, or all of the output means may be mounted onto a surface with flexible and/or (visco) elastic properties, such as a polymer foam or similar, which may enable adaptation of the output means to the target tissue surface and thus a more comfortable treatment.
In an example, at least a portion of at least one of the output means is releasably attached to the applicator. For example, the output means may comprise a cover, e.g., a single cover for all output means, or a plurality of covers, one per output means, or a mixture of both. Having such covers releasably attached to the applicator may be desirable for hygiene reasons. For example, after contact with a person's skin, such a cover may easily be removed, cleaned, disinfected and reused, or replaced with a new, possibly sterile one, if use of single use covers is desired. But it may also allow to adapt the output means, possibly on an individual basis, enabling an increase in comfort for the person to which the partial laser beams are to be applied. The same holds true if the output means as such are releasably attached to the applicator, either individually or as a whole, or a mixture of both. Also, having at least a portion of at least one of the output means releasably attached to the applicator may facilitate repair of the applicator, thus increasing its longevity.
In some examples, the applicator may be adapted such that the at least two partial laser beams are applied to at least 50%, preferably at least 80%, more preferably at least 90%, most preferably 100% of a target area, when the applicator is moved over the target area along a preferred direction of movement. This may allow seamless coverage of the target area, in turn leading to better, easier to control and more predictable results.
Generally, a target area may be understood throughout this disclosure as an area that is intended to be subjected to laser light. As such, in some examples, a target area may be understood to refer to areas in which a person loses hair. In other examples, a target area may also be understood as an area that is circumscribed by the outermost spots to which partial laser beams have been, or are to be, applied. In yet other examples, a target area may refer to the area to which the laser light of a single partial laser beam or a plurality thereof has been, or is to be, applied.
Additionally or alternatively, the applicator may be adapted such that the at least two partial laser beams are applied with an overlap of at most 50%, preferably at most 20%, more preferably at most 10%, even more preferably at most 1%, most preferably 0%, when the applicator is moved over a target area along a preferred direction of movement. While, generally speaking, simply overlapping the at least two partial laser beams may effectively eliminate any gaps in coverage—or, phrased differently: reduce the chance to “miss a spot”—, overlapping the at least two partial laser beams may at the same time lead to a less even application of the at least two partial laser beams in total, thereby possibly negatively affecting effectiveness and predictability.
Preferably, the applicator may be adapted such that the at least two partial laser beams are applied to at least 50%, preferably at least 80%, more preferably at least 90%, most preferably 100% of a target area as well as such that the at least two partial laser beams are applied with an overlap of at most 50%, preferably at most 20%, more preferably at most 10%, even more preferably at most 1%, most preferably 0%, when the applicator is moved over the target area along a preferred direction of movement. In other words, preferably, the applicator may be moved along a preferred direction of movement such as to provide substantially full coverage of a target area, however without overlapping the partial laser beams. This yields optimal and even coverage and hence maximizes effectiveness and predictability.
In an example, the applicator may comprise an indication of the preferred direction of movement perceivable by a user at least while the at least two partial laser beams are applied to the person. Thereby, it may be ensured that the applicator is indeed—at least substantially—moved along the preferred direction of movement, such that the above-described advantages may be realized.
For example, to achieve the above-mentioned, desired, substantially full coverage of a target area, however without overlapping the partial laser beams, the at least two output means may be arranged in at least one column comprising N output means, with an average distance l between the N output means, the N output means adapted to apply partial laser beams of average diameter D. Nis an integer (e.g. two, three or more). Then, the preferred direction of movement of the applicator may be defined by an angle with respect to the at least one column in the range of 0.5α to 1.5α, preferably 0.8α to 1.2α, more preferably 0.9α to 1.1α, most preferably 0.95α to 1.05α, wherein
α may be any angle between 0° and 90°. As will be discussed in further detail below, this ensures that the partial laser beams leave “tracks” on an area to which they are applied that join seamlessly, however without overlapping.
Each output means may apply a partial laser beam of a certain diameter. Such diameter may be a diameter of a circular cross section of a partial laser beam, or it may be an effective diameter in case of a partial laser beam of a non-circular (e.g., hexagonal, elliptic, etc.) cross section, as averaged over the circumference of that cross section. Such cross section may be understood as a cross section of the partial laser beam immediately where the partial laser beam is output from the respective output means. Additionally or alternatively, said cross section may for example also be understood as a cross section of the partial laser beam where the partial laser beam impinges onto a target, as defined, e.g., by a tissue surface of a person if the applicator is applied to the person (e.g. if the applicator and/or the output means are placed onto a tissue surface of the person). In some examples, e.g., if the partial laser beam is collimated, a cross section of the partial laser beam immediately where the partial laser beam is output from the respective output means may be the same as a cross section of the partial laser beam where the partial laser beam impinges onto a target. The above-used term average diameter may then refer to an average over the diameters of the partial laser beams output by the N output means in a column (or all output means of the applicator). In some examples, some or all of the N output means may each apply a single partial laser beam that may comprise the same, i.e., for example a constant, (effective) diameter.
Generally, a diameter and/or a cross section of a partial laser beam may correspond to (or at least be dependent on) a diameter and/or a cross section of a respective output means outputting the partial laser beam.
Throughout this disclosure, distances between output means are to be understood as measured from center to center of the respective output means. The center of an output means may be understood as the geometric center of a cross section of the output means. Such cross section may be understood to be a cross section of the output means immediately where it outputs a partial laser beam. The above-used term average distance may then refer to an average over the pairwise distances between adjacent output means of the N output means in a column (or over all output means of the applicator). In some examples, some or all of the N output means of a column may be arranged such that they comprise a same, i.e., for example a constant, distance to the respective adjacent output means.
In some examples, the at least two output means may be arranged in a plurality of columns and rows essentially perpendicular to each other. Such an arrangement may allow simultaneous application of a larger number of partial laser beams in a predictable manner, hence increasing efficiency without sacrificing predictability. Moreover, each column may be arranged in the manner just described, such that the partial laser beams corresponding to the output means comprised in the respective column are applied evenly and seamlessly as described above if the applicator is moved along the corresponding preferred direction of movement.
Additionally or alternatively, the distance between the columns of such an arrangement of output means may be chosen in such a way that the areas targeted by different columns of output means also join together substantially seamlessly, but possibly without overlapping, resulting in application of partial laser beams to at least 50%, preferably at least 80%, more preferably at least 90%, most preferably 100% of a target area (and/or an overlap of at most 50%, preferably at most 20%, more preferably at most 10%, even more preferably at most 1%, most preferably 0%), when the applicator is moved over the target area along a preferred direction of movement.
For example, when a first column comprises N output means, with an average distance l between the N output means, the N output means adapted to apply partial laser beams of average diameter D, then the first column may be spaced from an adjacent second column of (possibly also N) output means by a distance in the range of 0.5 L to 1.5 L, preferably 0.8 L to 1.2 L, more preferably 0.9 L to 1.1 L, most preferably 0.95 L to 1.05 L, wherein
N is an integer (e.g. two, three or more). Notably, an applicator with such an arrangement of output means in columns and rows may yield substantially even and seamless coverage of a target area when moved substantially along a preferred direction of movement, which may in this case be defined by an angle with respect to the columns in the range of 0.5α to 1.5α, preferably 0.8α to 1.2α, more preferably 0.9α to 1.1α, most preferably 0.95α to 1.05α, wherein
α may be any angle between 0° and 90°.
More generally, any at least two output means arranged in a two-dimensional pattern of points and adapted to apply partial laser beams of average diameter D may provide such substantially even and seamless coverage of a target area if the two-dimensional pattern of points is obtainable, from a column of points with an average distance l between the points, by translating one or more of the points of the column along a direction having an angle of, e.g. a with respect to the column, wherein
It is also within the scope of the present disclosure that the pattern of points is obtainable by translating one or more of the points of the column along a direction having an angle in the range of 0.5α to 1.5α, 0.8α to 1.2α, 0.9α to 1.1α, or 0.95α to 1.05α, wherein
α may be any angle between 0° and 90°. The corresponding preferred direction of movement may then correspondingly be defined by an angle with respect to the column of points in the range of 0.5α to 1.5α, preferably 0.8α to 1.2α, more preferably 0.9α to 1.1α, most preferably 0.95α to 1.05α, or α wherein
In examples, applicators according to the present invention may further comprise means for receiving the at least one laser beam, in particular from an articulated arm and/or fiber. The means for receiving render applicators according to the present invention particularly versatile as they may hence receive the at least one laser beam from an external source. This is of particular importance because high-energy laser light sources may be too large and unwieldy to be placed within or with the applicator. Also, providing an applicator with means for receiving the at least one laser beam from an external laser light source enables more freedom of design as less parts need to be accommodated within or at the applicator. This freedom may in turn also allow for a more ergonomic design of the applicator, in effect possibly increasing ease of use as well as control. Receiving the at least one laser beam from an articulated arm and/or fiber may further provide for significant freedom of movement, enabling virtually unrestricted movement of the applicator in three-dimensional space. This, too, may allow for a more ergonomic design of the applicator, increasing ease of use and possibly also control.
It is noted that the means for receiving may be generally realized as outlined herein. The means for receiving may, by way of example and not limitation, comprise an optical fiber and/or a free space beam path, wherein the latter may include one or more mirrors and/or lenses.
In another aspect, an applicator as described herein may be provided with an articulated arm and/or a fiber.
Additionally or alternatively, applicators according to the invention may further comprise beam expanding means. As discussed, the at least one laser beam is split into at least two partial laser beams. In some examples, the at least one laser beam may be expanded beforehand in order to allow for easier spitting. This may become ever more important the more partial laser beams are to be obtained from the at least one laser beam.
Additionally or alternatively, applicators according to the present invention may comprise reflective means, in particular a plurality of mirror segments. Reflective means may be used to (re)direct the at least one laser beam and/or the at least two partial laser beams. This may increase the freedom of design further, potentially enhancing the applicator's ergonomics, increasing ease of use and control. For example, the at least one laser beam may be received from a direction that is not substantially orthogonal to the application area (defined as the area circumscribed by the outermost output means of an applicator), but rather, e.g., substantially perpendicular thereto. This may in fact be desirable as it may allow the user to place a whole hand, or at least large parts thereof, on the applicator, resulting in easier and more controlled handling of the applicator. In fact, e.g., assuming the at least one laser beam is received from an optical fiber or articulated arm, the optical fiber or articulated arm may be easily integrated in a handle of the applicator. In some examples, the reflective means may double as means for splitting the at least one laser beam. For example, if a plurality of mirror segments is used that are positioned and/or oriented differently, different portions of the—possibly expanded—at least one laser beam may be guided in different directions, e.g., towards different output means, hence obtaining at least two partial laser beams by virtue of the reflective means alone.
Additionally or alternatively, applicators according to the present invention may comprise a plurality of apertures, each aperture corresponding to at least one partial laser beam. Such apertures may be used for, or at least in, splitting the at least one laser beam. For example, the at least one laser beam may be expanded and then (re)directed towards the plurality of apertures. The plurality of apertures then transmits at least a part of the at least one laser beam, thus letting at least two partial laser beams pass.
Additionally or alternatively, applicators according to the present invention may also comprise a plurality of lenses, each lens corresponding to at least one partial laser beam. Similar to a plurality of apertures as just discussed, a plurality of lenses may be used for, or at least in, splitting the at least one laser beam. For example, the plurality of lenses may not be contiguous, resulting in gaps in between the lenses, such that the at least one laser beam may be split into at least two partial laser beams when directed towards the plurality of lenses. In addition, and in this respect different from apertures, lenses may also (re)focus and/or collimate the at least one laser beam and/or the at least two partial laser beams, thereby increasing effectiveness, efficiency and control.
In some examples, there may not be a one-to-one correspondence between partial laser beams, output means and apertures or lenses. In some examples, more than one partial laser beam may correspond to a single output means and/or an aperture and/or a lens. In yet other examples, at least one output means and/or an aperture and/or a lens my not correspond to a partial laser beam, e.g., because there are fewer partial laser beams than there are output means and/or apertures and/or lenses. Notably, therefore, the correspondence between partial laser beams, output means and apertures or lenses if expressed as an average may not only be given in terms of an integer, but also by a rational number.
The skilled person readily understands that, thanks to the reversibility of optical paths, the above-discussed means, including the means for splitting the at least one laser beam, may in principle be arranged in any, arbitrary order and combination.
In an example, an applicator according to the present invention may comprise a flat mirror and/or a plurality of hexagonal lenses and/or one or more diffractive optical elements or similar which split a beam essentially like a plurality of hexagonal lenses. For example, the flat mirror may be adapted to direct a laser beam onto the plurality of hexagonal lenses. Using hexagonal lenses may be advantageous as they may be grouped together to be contiguous. If at least one laser beam—for example an expanded one—is then directed towards the plurality of hexagonal lenses, (almost) no laser light, i.e., energy, may be lost as there are no (non-transparent, i.e., “dead”) spaces between the lenses. Still, each hexagonal lens of the plurality of hexagonal lenses focuses a portion of the at least one laser beam as directed towards it. The plurality of hexagonal lenses may then pass on at least two partial laser beams, in particular if the plurality of hexagonal lenses each correspond to one of the at least two output means. Using a plurality of hexagonal lenses is advantageous as this may optimize usage of the at least one laser beam, for example along its full diameter, especially assuming its cross section is substantially circular. However, other cross sections, such as square, rectangular or elliptic ones, are conceivable and any sort of lenses, in particular hexagonal lenses, may readily be arranged as to adapt to the respective cross section of the at least one laser beam. This in turn ensures that as much of the energy of the at least one laser beam is funneled into the at least two partial laser beams. Moreover, as using a plurality of hexagonal lenses may allow to fully exploit the at least one laser beam across its—possibly substantially circular—cross section, the remaining applicator and especially its optical components may be quite simple. For example, one may use a flat mirror to (re)direct the at least one laser beam as splitting and (re)focusing will be achieved by means of the hexagonal lenses either way, with limited to no loss.
It is noted that the means for splitting may be generally realized as outlined herein. Additionally or alternatively, also a polarizing beam splitter or any other suitable means may be used to split the laser beam, for example.
In another aspect, the present invention relates to methods for ameliorating alopecia, for improving quality, color and/or density of hair, and/or for improving a condition of a scalp of a person by laser light. For example, such methods may comprise the use of an applicator according to the first aspect of the invention, hence entailing all the above-described advantages.
Whether or not using an applicator according to the first aspect of the present invention, a method for ameliorating alopecia, for improving quality, color and/or density of hair, and/or for improving a condition of a scalp of a person by laser light according to a further aspect of the invention may also comprise directing at least one laser pulse comprising a wavelength onto a tissue surface of the person. The wavelength may be chosen to be a wavelength that is highly absorbed by the tissue surface of the person. An applicator for that purpose may comprise a laser source or may receive laser light from an external source. The tissue surface of the person may be a surface of a scalp of the person. The wavelength may be selected from a wide range, e.g., from near infrared to far infrared. In preferred examples, wavelengths that are highly absorbed in water and/or that have a low penetration depth δ with respect to the tissue surface may be used.
For example, the wavelength of the at least one laser pulse may be between approximately 1.8 micrometers and approximately 11 micrometers, preferably between 2.6 micrometers and 3.2 micrometers or between 9.1 micrometers and 10.2 micrometers. In some examples, the penetration depth δ may be smaller than 30 micrometers, preferably smaller than 10 micrometers, and even more preferably smaller than 4 micrometers. In some examples, the penetration depth δ may be approximated to be 1 micrometer, e.g., for a Er:YAG laser with a wavelength of 2.94 micrometers (or, more generally, for any wavelength between 2.9 micrometers and 3.2 micrometers, or even between 2.6 micrometers and 3.2 micrometers). In other examples, the penetration depth δ may be approximated to be 15 micrometers, e.g., for a CO2 laser with a wavelength of 10.64 micrometers (or, more generally, for wavelengths between 9 micrometers and 11 micrometers), or the penetration depth δ may be approximated to be 3 micrometers, e.g., for a Er, Cr:YSGG laser with a wavelength of 2.78 micrometers (or, more generally, for wavelengths between 2.6 micrometers and 2.9 micrometers). In yet other examples, e.g., for a diode or Ho:YAG or Tm:YAG laser with a wavelength between 1.8 micrometers and 2.2 micrometers, the penetration depth δ may be approximated to be 100 micrometers.
The at least one laser pulse may be delivered individually or in a pulse sequence.
The at least one laser pulse may be provided with a fluence F such that it is ablative (creating microwounds on and/or in the tissue surface and thus stimulating regeneration of the tissue surface and/or hair follicles) or non-ablative with respect to the tissue surface of the person onto which it is directed. As used herein, the term fluence F is defined as F=E/Aspot, wherein E is an energy of the at least one laser pulse and Aspot is a spot size area of the at least one laser pulse at the tissue surface onto which the at least one laser pulse is directed (e.g., the minimum surface in which at least 90% of the energy E of the at least one pulse is deposited). When the fluence F of the at least one laser pulse is increased to reach values above an ablation threshold, the tissue surface is vaporized and/or ablated. The depth of such ablation increases with increasing fluence F.
In some examples, the fluence F of the at least one laser pulse may be chosen to be below the ablation threshold of the tissue surface. For very short pulses, where heat diffusion into a tissue beneath the tissue surface onto which the at least one laser pulse is directed during the pulse is not appreciable (e.g. pulse durations below 10 microseconds), an ablation threshold fluence Fthr can be approximately calculated as Fthr≈H×δ, where H≈1 J/mm3 is the tissue's specific heat of ablation (i.e. the energy per tissue volume added to generate ablation), and δ is the penetration depth in the tissue volume (that may be approximated for various laser sources or wavelengths as outlined further above). For example, given a penetration depth δ of 1 micrometer, e.g., of a Er:YAG laser, the ablation threshold fluence Fthr for a very short pulse would be equal to about 0.1 J/cm2.
The ablation threshold becomes higher for longer pulse durations since thermal diffusion deeper into the tissue during a pulse effectively prolongs the at least one laser beam's thermal penetration depth. For example, for typically encountered Er:YAG pulse durations between 50 and 1500 microseconds, the ablation threshold fluence Fthr is between 0.5 J/cm2 and 3 J/cm2, resulting in approximately 10-times higher effective specific heat of ablation (H≈10 J/mm3). In some, non-ablative examples, the fluence is chosen to be below 0.1 J/cm2 or below 0.5 J/cm2 (particularly for pulse durations of 5 to 1500 microseconds, 5 to 500 microseconds, 50 to 500 microseconds or 50 to 100 microseconds). It may also be chosen below 1 J/cm2 or below 3 J/cm2 (particularly for pulse durations between 50 to 1500 microseconds, 100 to 1500 microseconds, or 500 to 1500 microseconds). In ablative examples, the fluence may be chosen above the thresholds listed in the preceding sentences, particularly at least 0.5 J/cm2, at least 3 J/cm2, at least 5 J/cm2, at least 10 J/cm2 or at least 50 J/cm2. In another example, the fluence F of the at least one laser pulse may be chosen to be above the ablation threshold, e.g., the fluence F may be selected to be between 1 J/cm2 and 50 J/cm2, preferably between 3 J/cm2 and 10 J/cm2.
It is to be noted that for significantly longer pulse durations (of up to 2000 microseconds), heat diffuses deeply into the tissue during a pulse (up to about 50 micrometers). Therefore, the pulse duration has a significant influence on the ablation threshold fluence Fthr only for lasers with a (n optical) penetration depth δ that is comparable to or below about 50 micrometers.
In a preferred example, laser pulses or pulse sequences—for example the at least one laser pulse discussed above—may be delivered, e.g., by a Er:YAG laser, in a recently disclosed dual tissue regeneration mode, as described in European patent application EP 18172363 which is incorporated by reference herein. This dual tissue regeneration mode comprises very short laser pulses or pulse sequences that create a non-ablative thermal “needling” (i.e., triggering) effect, with the laser pulses so short that a laser pulse delivery time and a temperature diffusion time combined are shorter than 900 microseconds. More specifically, an energy delivery time ted of at least one of such laser pulse, during which a second half of an energy of the laser pulse is delivered, is chosen sufficiently short, so that, given a wavelength and thus a corresponding penetration depth δ of the laser pulse (e.g. as approximated by the values indicated further above), ted+(i/A) (δ+√(2 A ted))2<900 microseconds, wherein A=0.1 mm2 s−1. Laser pulses of such characteristics have been found to be particularly effective for ameliorating alopecia, for improving quality, color and/or density of hair, and/or for improving a condition of a scalp. Specific parameters of such pulses as disclosed by European patent application EP 18172363 are an integral part of the present disclosure.
In some examples, the energy delivery time ted of the at least one laser pulse may be smaller than 600 microseconds, more preferably smaller than 300 microseconds and even more preferably smaller than 100 microseconds. Yet, it may in some examples be desirable if the energy delivery time ted is not shorter than approximately 100 nanoseconds.
Pulses, such as the pulses in the above example, e.g., the at least one laser pulse discussed further above, may also be delivered within and/or as a pulse sequence S. A repetition time between subsequent pulses of the pulse sequence S, ts, may be shorter than about 200 milliseconds, preferably shorter than 100 milliseconds, most preferably shorter than 50 milliseconds.
Further, a number Ns of pulses of the pulse sequences S may be selected so that the total duration of the pulse sequence S, ttot=Ns×ts, is shorter than 10 seconds, preferably shorter than 3 seconds, most preferably shorter than 0.5 second.
At least some of the laser pulses delivered on the tissue surface, e.g., the at least one laser pulse discussed above, or portions thereof, may be adapted to comprise a diameter of at least 10 micrometers, for example a diameter from 50 micrometers to 800 micrometers, or from 100 micrometers to 500 micrometers.
In another example, wavelengths that are not absorbed well by water and/or by the tissue surface but rather penetrate deeper into the tissue beneath the tissue surface may be used. Such wavelengths preferably lie in the range from approximately 800 nanometers to approximately 2000 nanometers. With such wavelengths, localized absorption and heating of absorbing targets inside the volume beneath the tissue surface onto which laser pulses, e.g., the at least one laser pulse discussed above, are directed may be achieved.
The concept of selective photothermolysis, which applies to lasers that penetrate below the tissue surface, enables either selective targeting or non-selective heating of the volume beneath the tissue surface onto which laser pulses, such as the at least one laser pulse discussed above, are directed by modifying the laser pulse duration and fluence F.
Upon irradiation of tissue with a suitable, short laser pulse, energy is deposited in an absorbing structure before much heat can be transferred to surrounding tissue by conduction. The resulting temperature rise in an optically and thermally homogenous absorbing structure is thus directly proportional to the absorbed heat, which is in turn proportional to the fluence of the laser pulse, e.g., the fluence F of the at least one laser pulse discussed above, in the target. In general, however, a significant fraction of the absorbed heat may diffuse away from the absorbing structure during laser exposure, which reduces a peak target temperature and impairs a spatial selectivity of the heating, even if the chosen wavelength provides for a selective absorption of laser energy. Therefore, selection of a suitable laser pulse duration, which determines the spatial confinement of absorbed heat in absorbing structures, is very important. Only laser pulse durations that are not significantly longer than about 10 times the thermal relaxation time τ enable a maximal temperature rise in the targeted absorbing structure. The relaxation time depends on the penetration depth (δ) as τ≈δ2/D where D is the thermal diffusivity of the tissue (for skin D≈1.10−7 M2/s). For example, for the Er:YAG laser with δ≈1-5 μm, depending on the dryness of the skin, the thermal relaxation time of epidermis is estimated to be in range from 0.01-0.25 milliseconds, and the pulse duration should not be significantly longer than about 0.1-2.5 ms. Otherwise, the heat absorbed locally during a (relatively long) pulse duration will flow also to surrounding tissue, such that temperature will not be maximal. Here, the relaxation time T represents a time interval in which an amplitude of a hypothetical temperature rise decreases approximately by a factor of 2 (due to, e.g., diffusion of heat into surrounding tissue).
For example, size-dependent targeting of microscopic islets causes them to heat up, causing a temperature gradient and subsequent heat transfer between the microscopic islets and the surrounding tissue. The pulse duration may be selected as a function of the size of one or more microscopic islets.
In an example, an Nd:YAG laser with a wavelength of 1064 nanometers may be used. The penetration depth δ of an Nd:YAG laser below the skin surface is about 1 cm, meaning it is a relatively deep penetrating laser. This wavelength is absorbed in melanine and may even, under certain circumstances, be used for hair removal when pulse duration and fluence are adjusted to maximally increase a peak target temperature in hair follicles, causing its destruction. In contrast, pulse duration and fluence may also be adapted to either cause fractional heating of microscopic islets under the tissue surface, or to achieve bulk heating of the tissue surface onto which laser pulses are directed. Both effects can stimulate regeneration of tissue and hair follicles. For example, shorter pulses of approximately 0.1 milliseconds to 2 milliseconds with low fluences of approximately 0.5 J/cm2 to approximately to J/cm2 may be used for stimulation. In another example, longer pulses or longer pulse sequences (from approximately 50 milliseconds to approximately 10 seconds) with higher fluences (from approximately 20 J/cm2 to approximately 1000 J/cm2) may be used. In both examples above, the power of the laser pulse is below the threshold for reaching the maximum peak temperature (e.g. critical temperature above which a permanent damage occurs) in the hair follicles.
In some examples, multiple laser modes may be used together, e.g., intermittently or concurrently, for example a combination of microwounding using the ablative method discussed above and stimulation using the non-ablative method discussed above.
The described methods may be used in combination with other topical or systemic therapies that could further increase the effect of ameliorating alopecia, improving quality, color and/or density of hair, and/or improving a condition of a scalp of a person. In an example, different growth factors or patient-derived platelet-rich plasma (PRP) may be used. PRP is a concentrated suspension of autologous platelets suspended in a small amount of plasma after centrifugation. Platelets play a fundamental role in hemostasis and are a natural source of growth factors. After preparation, PRP may be subcutaneously injected with several injections covering a target area. Alternatively, in case ablative techniques (e.g. using ablative wavelengths), which result in microwounds on and/or in the tissue surface, are used, PRP could be only topically applied over the target area without the need for injections, as PRP is then delivered to the scalp directly through the laser-induced microwounds.
In yet another aspect, the present invention relates to the use of laser pulses for ameliorating alopecia, improving quality, color and/or density of hair, and/or improving a condition of a scalp of a person. In particular, laser pulses that correspond in one or more or even all respects to the at least one laser pulse discussed above may be used.
Possible examples of the present invention will be described in more detail in the subsequent detailed description with reference to the following figures:
For the sake of brevity only a few examples will be described in the following. The skilled person will recognize that the specific features described with reference to these examples may be modified and combined differently and that individual features may also be omitted if they are not essential. The general explanations in the sections above will also be valid for the following more detailed explanations.
Applicator 100 may comprise beam expanding means 130, and laser beam 110 may be expanded by means of it. In the example of
After having passed the beam expanding means, laser beam 110 impinges upon reflective means 140 of applicator 100. In the example of
In some examples that comprise mirror segments like mirror segments 142 which are oriented substantially parallel to laser beam 110 as it is received, these mirror segments may not be reflective. In yet other examples, there may be more than two kinds of mirror segments such as mirror segments 142 and 144, each kind arranged at a specific angle with respect to the direction along which laser beam 110 is received.
In the example of
Due to the arrangement of mirror segments 142 and 144, laser beam 110 is split into a number of laser beam strips (not shown/labelled) that propagate in a direction that is substantially perpendicular to the direction from which laser beam no is initially received. In some examples, the number of resulting laser beam strips may be equal to the number of mirror segments such as mirror segments 144. In the example of
The laser beam strips are (re)directed towards at least two output means 160. Output means 160 may comprise an elongated shape that may extend substantially perpendicular to the direction from which laser beam 110 is initially received. In the example of
Output means 160 may be arranged to be placed on a surface of a target, e.g. a surface of a scalp. Applicator 100 may comprise an essentially plane lower surface from which each output means 16o protrudes. Output means 160 may comprise a width (understood here with respect to the drawing plane of
Output means 160 are arranged such that hair can be accommodated at least partly in between them. In the example of
Output means 160 may be adapted such that laser light is output with a predetermined diameter onto a surface of a target if the applicator is placed onto the surface. In some examples, the laser light may be output as a diverging beam (as shown in
Output means 160 may comprise output lenses 162. Output lenses 162 may focus partial laser beams 120 that are obtained from the laser beam strips (details below in the context of
Applicator 200 comprises at least two output means 260. Output means 260 each comprise a core 261 (labelled collectively in
In the example of
Having output means such as output means 260 comprise a cover such as cover 269 may be advantageous for hygiene reasons. For example, after contact with a person's skin, such a cover may easily be removed, cleaned, possibly disinfected and reused, or it may be replaced with a new, possibly sterile, one.
Applicator 200 may comprise lenses 250. In the example of
In the example of
Reflective means 240 splits laser beam 210 into a number of laser beam strips that propagate in a direction that is substantially perpendicular to the direction from which laser beam 210 is initially received, similar as described with respect to laser beam 110 and reflective means 140 of
Different from applicator 200, applicator 300 comprises output means 360 (labelled collectively) that are as a whole releasably attached or attachable, respectively, to applicator 300 (as opposed to output means 260 of the example of
In some examples, output means such as output means 360 may be releasably attached or attachable, respectively, on an individual basis, i.e., each output means such as output means 360 may be releasably attached or attachable, respectively, independently of other output means 360. In some examples, only some of output means such as output means 360 may be releasably attached or attachable, respectively, either collectively or individually. In yet other examples, none of output means such as output means 360 may be releasably attached or attachable, respectively, neither as a whole nor in portions.
Just as output means 160 of the example of
In another example, the proximal end of at least one, more than one but not all, or all of the output means may be attached to and/or enclosed by a base surface comprising flexible and/or (visco) elastic properties, such as a polymer foam or similar. In yet another example, cover 269 may be attached onto such a base surface comprising flexible and/or (visco) elastic properties. This may enable better adaptation of the output means, e.g., to a scalp shape and therefore a more comfortable procedure.
Again, the skilled person will readily understand that partial laser beams such as partial laser beams 420 may then accordingly be applied in a corresponding pattern, i.e., lattice structure. The skilled person understands that this correspondence between arrangement of output means and arrangement of applied partial laser pulses applies throughout the entire present disclosure.
Accordingly, partial laser beams 520 are applied in columns 565a-565e. In the example of
Columns 565b and 565c as well as 565c and 565d may be spaced apart a distance L1.L1 is a rational number approximately given by
(details below).
Columns 565a and 565b, and columns 565d and 565e are spaced apart a distance L2.L2 is a rational number approximately given by
(details below).
As illustrated in
α may be any angle between 0° and 90°.
As can be seen, the angle may be selected such that tracks 525 may join (approximately) seamlessly, i.e., the total area to which partial laser beams 520 are applied when applicator 500 is moved along direction 505 is contiguous. At the same time, tracks 525 do not overlap. As such, the arrangement of output means underlying the pattern of partial laser beams 520 of
Direction 505 may be indicated (e.g. on the applicator) such that it is perceivable by a user at least while applicator 500 is in use. For example, direction 505 may be printed onto applicator 500, for example on a backside of applicator 500, or onto any other side with no output means arranged thereon. In other examples, direction 505 may be indicated on a display, e.g., on a computer monitor or a similar digital display, which may either be arranged at applicator 500 or remote therefrom. In yet other examples, direction 505 may be indicated by means of haptic feedback. For example, applicator 500, or at least a handle thereof, could be caused to vibrate in order to notify the user whether he/she is moving applicator 500 along direction 505.
The above factors
respectively, may be derived as follows: Let ΔL denote a width of a horizontal cut through a single track 525. Horizontal is to be understood with respect to the drawing plane of
wherein
as above. Recasting this,
may be obtained. As is well known, sin2α+cos2 α=1, i.e., cos α=√{square root over (1−sin2α)}. Substituting
may be obtained. Exploiting this,
may be obtained.
Now to reach the center of a partial laser beam of, e.g., column 565d starting from the center of a corresponding laser beam of, e.g., column 565c, one must traverse approximately the distance L1, or approximately 4 times ΔL. Hence,
Similarly, to reach the center of a partial laser beam of, e.g., column 565e from the center of a corresponding laser beam of, e.g., column 565d, one must traverse approximately the distance L2, or approximately 3 times ΔL. Hence,
In this context, partial laser beams of different columns may be said to correspond if they may be arranged in a single row that extends perpendicular to the columns.
The pattern of partial laser beams 520 of diameter D shown in
α may be any angle between 0° and 90°. Adjacent columns obtained in this manner may then approximately be spaced apart a distance L given by
times the distance by which the respective points have been translated along the direction having the angle α with respect to the column.
Arranging output means of an applicator such as applicator 500 in a manner to provide such a pattern of partial laser beams such as partial laser beams 520 ensures that tracks such as tracks 525 join seamlessly, however without overlapping. That is, arranging output means of an applicator such as applicator 500 in a manner to provide such a pattern of partial laser beams such as partial laser beams 520 ensures that partial laser beams such as partial laser beams 520 cover a target area evenly and seamlessly, i.e., the area on which partial laser beams such as partial laser beams 520 impinge is contiguous.
However, different from applicators 100, 200 and 300 of
After being (re)directed by reflective means 640, laser beam 610 impinges on an array of lenses 650. In principle, lenses 650 could be similar to lenses 250 and 350 of
Partial laser beams 620 are guided into output means 660. There may be as many output means 660 as there are lenses 650 and partial laser beams 620. Regarding the shape and size of output means 660 as well as regarding their further characteristics, such as their material composition, it is referred to the above explanations concerning output means 160, 260 and 360 of
In particular, also output means 660 are arranged such that hair can be accommodated at least partly in between them. That is, output means 660 define three-dimensional voids 670 in between them. Voids 670 are sized as to accommodate hair at least partly. Just as output means 660 themselves, voids 670 do not need to be the same. Rather, voids 670 may differ in size and shape.
As can be gathered from
In other examples, lenses 750 may also be arranged at a distal end of a common base block such as common base block 768, i.e., at an end of the common base block through which a laser beam such as (re)directed laser beam 710 passes last. Then, the common base block 768 may function like an aperture.
Moreover, lenses 850 are arranged in a contiguous manner. As shown in
The skilled person will understand from the above explanations that the various means discussed herein do not need to be implemented as a single element each. In some examples, certain means may be implemented by a plurality of elements that may or may not simultaneously function as other means or parts thereof, too. For example, while in the example of
It is emphasized again that the skilled person will readily understand that all the means discussed herein, including the means for splitting at least one laser beam, may be arranged in any order and combination thanks to the reversibility of optical paths.
The skilled person also understands that wherever reference is made to a definite geometrical relation the respective expressions should be understood to also mean relations that are substantially equal to the definite geometrical relation explicitly referred to, i.e., “perpendicular” should be understood to mean “essentially perpendicular”, “angled at 45°” should be understood to mean “angled at substantially 45°”, and so forth.
A method for hair scalp regeneration according to the current invention (e.g., for ameliorating alopecia, for improving quality, color and/or density of hair, and/or for improving a condition of a scalp) may comprise any one, two or three of the following three steps either performed separately or as a combination of any of the three steps in any order of succession.
In one of the embodiments, this step is performed with an Erbium laser with a wavelength between 2.5 and 3.5 μm, such as for example Er:YAG (2940 nm) or Er, Cr:YSGG (2780 nm). The laser energy is delivered in a pulse train sequence consisting of N subablative laser pulses where N=1-100, preferably N=5-40 separated by pulse separation time tser=5-500 ms, preferably tser=20-250 ms, and characterized by one or more (or all) single laser pulse durations of less than 5 ms, preferably less than 1 ms, and one or more (or all) single pulse fluences Fo below 2.5 J/cm2, preferably below 1 J/cm2, most preferably below 0.5 J/cm2. The cumulative fluence Fc=N×Fo is for N greater than 1 in the range of 1-50 J/cm2, preferably up to 20 J/cm2 with overall pulse sequence duration tc=N×tser being in the range of 20 ms to 10 s, preferably in the range of 100 ms−2000 ms. The combination of parameters N, Fo and tser must be chosen such that the pulse sequence does not result in an appreciable tissue ablation.
Ablative resurfacing may be performed in order to produce small epidermal perforations. The goal of these perforations is to trigger scalp regeneration via tissue healing mechanisms, and/or to facilitate penetration of PRP (Platelet-Rich Plasma) or any other medications intended for the treatment of hair loss and other scalp related indications. For example, the medications may be applied by simply rubbing them thoroughly in, for example, circular motion over the pre-drilled area.
In one of the embodiments this step is performed with an Erbium laser with a wavelength between 2.5 and 3.5 mm, such as for example Er:YAG (2940 nm) or Er, Cr:YSGG (2780 nm). The laser energy may be delivered in N=1-10 pulses separated by tser=20-500 ms, preferably tser=50-250 ms, and characterized by one or more (or all) single laser pulse durations of less than 5 ms, preferably less than 1 ms, and one or more (or all) single pulse fluences Fo above 2 J/cm2, preferably above 5 J/cm2, most preferably above 8 J/cm2.
Biomodulation may consist of non-ablative non-thermal (average power density less than 0.2 W/cm2) or minimally thermal (average power density less than 3 W/cm2) stimulation of the scalp.
In one of the embodiments, minimally thermal stimulation is performed with an Nd:YAG laser (1064 nm) with an average power density below 3 W/cm2, preferably below 0.5 W/cm2. The treatment duration may be adjusted from 0.5 s to 5 s to deliver from 0.1 J/cm2 to 1.5 J/cm2.
Other preferred embodiments include the following diode lasers, with the treatment duration adjusted from 0.5 s to 5 s to deliver from 0.1 J/cm2 to 1.5 J/cm2; 1064 nm diode with power density below 0.5 W/cm2 preferably below 0.2 W/cm2; 630-680 nm diode with power density below 0.3 W/cm2 preferably below 0.1 W/cm2; 960-980 nm diode with power density below 0.3 W/cm2 preferably below 0.2 W/cm2.
| Number | Date | Country | Kind |
|---|---|---|---|
| 20176304.2 | May 2020 | EP | regional |
