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WO2017223331A1 - Traitements sélectifs de la peau utilisant des dispositifs à lumière pulsée intense équivalente au laser - Google Patents

Traitements sélectifs de la peau utilisant des dispositifs à lumière pulsée intense équivalente au laser Download PDF

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Publication number
WO2017223331A1
WO2017223331A1 PCT/US2017/038781 US2017038781W WO2017223331A1 WO 2017223331 A1 WO2017223331 A1 WO 2017223331A1 US 2017038781 W US2017038781 W US 2017038781W WO 2017223331 A1 WO2017223331 A1 WO 2017223331A1
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WO
WIPO (PCT)
Prior art keywords
ipl
band pass
pass filter
source
light
Prior art date
Application number
PCT/US2017/038781
Other languages
English (en)
Inventor
Yacov Domankevitz
Israel Schuster
Original Assignee
Lumenis Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lumenis Ltd. filed Critical Lumenis Ltd.
Priority to CN201780038674.2A priority Critical patent/CN109788946B/zh
Priority to IL303752A priority patent/IL303752A/en
Priority to IL263143A priority patent/IL263143B2/en
Priority to EP17816217.8A priority patent/EP3474762A4/fr
Priority to CA3026197A priority patent/CA3026197A1/fr
Priority to CN202310077226.0A priority patent/CN115998417A/zh
Publication of WO2017223331A1 publication Critical patent/WO2017223331A1/fr
Priority to US17/836,160 priority patent/US11813474B2/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/203—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser applying laser energy to the outside of the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
    • A61B18/26—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor for producing a shock wave, e.g. laser lithotripsy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00452—Skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B2018/1807—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using light other than laser radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/065—Light sources therefor
    • A61N2005/0654—Lamps

Definitions

  • the present invention relates to light treatments applied to human skin tissue and in particular to light treatments utilizing selective band pass filters in Intense Pulsed Light devices.
  • Optical energy radiation is a known modality for the treatment of skin disorders.
  • the irradiated optical energy will preferably be absorbed in the skin.
  • Light absorbance in the skin is dominated by three endogenous chromophores: water, melanin and hemoglobin.
  • a correct matching between a light wavelength or a spectrum of wavelengths, with a targeted chromophore, may lead to an optical energy absorbance which may be followed by a clinical effect due to one or more of
  • selective laser treatment may be achieved by selecting the right wavelength to the right chromophore as mentioned above, by applying an energy pulse which is shorter or equal to the thermal relaxation time of the target chromophore and by delivering above-threshold energy to the target tissue.
  • IPL devices emit polychromatic, non-coherent and non-collimated light in a spectrum range from about 400nm to about 1 ,400nm, and are normally delivered in a variety of pulse durations. As such, IPL is less selective since different chromophores may be targeted in this range.
  • One option to improve selectivity of IPL-generated light energy is by using filters. Cut off filters are used on the lower end of the emission spectrum of IPL devices and cut on filters are used on the upper end of the emission spectrum. Such filters may improve treatment selectivity or reduce parasitic wavelengths which may put the patient at risk, such as ultra-violet or increased bulk heating such as is possible with the presence of an infrared component in the light emitted. Common medical IPL cut off filters include 550, 560, 570, 590, 615, 645, 695, 755 and 780 nm filters. Cut off and cut on filters may be used together to create what is termed a band pass filter.
  • Band pass filters provided by some providers, such as Alma Lasers, for example, provide a narrow spectrum IPL based treatment within the range of 500nm-600nm for the treatment of vascular lesions which are targeted at larger blood vessels.
  • An alternative narrow band pass filter is provided in the range of 550nm-600nm for skin rejuvenation.
  • One of the problems with such filters is that, in the filtering process, they also remove part of the total optical energy produced by the light source, which is an IPL light source. Therefore, in order to produce a clinical effect by meeting the threshold-energy requirement mentioned above, only a limited amount of the spectrum can be removed.
  • vascular lesions are treated by targeting intravascular chromophore of oxyhemoglobin which has light absorption peaks at 418nm, 542nm and 577nm.
  • the most common vascular lasers are KTP, 532nm, pulsed dye laser (PDL) 585nm-595nm, Alexandrite 755nm, diode laser 940-980 nm and Nd:YAG 532 or l,064nm.
  • PDL pulsed dye laser
  • An IPL light source may also be used for the treatment of vascular lesions, as mentioned above, using filters which include at least one of these absorption peaks and remove damaging UV wavelengths and/or infrared wavelengths which may cause collateral thermal damage.
  • filters which include at least one of these absorption peaks and remove damaging UV wavelengths and/or infrared wavelengths which may cause collateral thermal damage.
  • Two companies, Lumenis and Palomar provide such dual band filters. For example, in the vascular dual band filter, the shorter wavelengths are used for smaller superficial vessels and the longer wavelengths are used for larger deeper vessels.
  • Pigmented lesions are also treated by lasers by targeting melanin in melanosomes as the target chromophore with lasers such as KTP (532 nm), Ruby (694 nm), alexandrite (755 nm), etc. using a variety of pulse durations ranging from milliseconds down to picoseconds.
  • IPL may also be used for some pigmented lesions such as dyschromia or solar lentigines.
  • filters which generate the appropriate spectrum of optical energy provided that the spectrum is wide enough such that a sufficient amount of fluence reaches the target tissue, an IPL-powered device may be used to treat at least some pigmented lesions.
  • different chromophores may be targeted and selectivity may be decreased.
  • short pulses may be required to confine the area or volume of any thermal effects in the target tissue. These short pulses may be in the range of nanoseconds or less while IPL offers pulses in the range of milliseconds only.
  • IPL single light source
  • a device for the cosmetic treatment of vascular lesions on skin tissue which is an equivalent of a laser with an operating wavelength of 532nm, includes: an intense pulsed light (IPL) source, the IPL source being activatable; it further includes a band pass filter which blocks substantially all but one range of wavelengths of light emanating from the IPL source when activated; the band pass filter permits transmission of light from the IPL source when activated in the range of about 525nm to about 585nm; the IPL with the band pass filter provides equivalent cosmetic treatment as a laser with an operating wavelength of 532nm.
  • IPL intense pulsed light
  • a method of providing cosmetic treatment equivalent to a 532nm laser on a body vascular region includes: providing an intense pulsed light (IPL) source; interposing a band pass filter between the IPL source and the body vascular region; the band pass filter is of a type that substantially passes light in the range of about 525nm to about 585nm; the method further includes activating the IPL source; the filtered light impinging on the vascular body portion provides cosmetic treatment equivalent to that of the 532nm laser.
  • IPL intense pulsed light
  • a cosmetic method of providing light treatment to skin tissue includes providing an intense pulsed light (IPL) source; interposing a band pass filter between the IPL source and the body vascular region; the band pass filter passes light in the range of about 525nm to about 585nm; the method further includes activating the IPL source and applying it to the skin tissue, wherein the filtered light impinging on the skin tissue provides equivalent treatment to that of a 532nm laser.
  • IPL intense pulsed light
  • a band pass filter is the equivalent to a 532nm laser impinging on skin tissue; the band pass filter is constructed to pass light through the filter
  • a cosmetic method of providing light treatment to skin tissue includes the steps of providing an intense pulsed light (IPL) source; interposing a band pass filter between the IPL source and the skin tissue; the band pass filter passes light in a selected range of wavelengths with an average absorption coefficient equivalent to that of a selected laser light source; the method further includes activating the IPL source and applying it to the skin tissue, wherein the filtered light impinging on the skin tissue provides equivalent treatment to that of the selected laser light source.
  • IPL intense pulsed light
  • a cosmetic method of providing an intense pulsed light (IPL) source equivalent in treatment effect to a selected laser light source includes for the selected laser light source of a specific wavelength, determining the average absorption coefficient of the specific wavelength in skin tissue; and, selecting a band pass filter with a substantially equivalent average absorption coefficient in skin tissue.
  • the skin tissue may be one or more of: absorption in blood and absorption in melanin.
  • the IPL source further includes a body portion which includes the IPL source and an opening in the body portion to accept one or more band pass filters and wherein the one or more band pass filters are filters which pass different ranges of light from the IPL source to the skin tissue.
  • the one or more band pass filters may be in one or more of the following ranges: 560-690nm; 675 - 900nm; 700 - 800nm; 725 - 775nm; 940 - 980nm.
  • a method of selecting an IPL light source having a band pass filter equivalent to a specified wavelength laser light source for providing cosmetic treatment of skin tissue includes the steps of: selecting a laser light source of a specified
  • the target may be skin tissue.
  • a method of selecting an IPL light source having a band pass filter equivalent to a specified wavelength laser light source for providing cosmetic treatment of skin tissue includes the steps of: selecting a laser light source of a specified
  • activating the laser light source directing the laser light source at a target; measuring the average depth of penetration of the selected laser in the target; storing the depth of penetration; selecting a band pass filter; activating the IPL light source;
  • a band pass filter is an equivalent to a 595nm laser impinging on skin tissue; the band pass filter is constructed to pass light through the filter substantially in the 560nm to 690nm range.
  • the light may be an IPL light source.
  • a band pass filter is an equivalent to a 755nm laser impinging on skin tissue; the band pass filter is constructed to pass light through the filter substantially in the 700nm to 800nm range.
  • the light may be an IPL light source.
  • a device for the cosmetic treatment of vascular lesions on skin tissue wherein the device is an equivalent of a laser having an operating wavelength of 595nm, includes an intense pulsed light (IPL) source, the IPL source being activatable; a band pass filter which blocks substantially all but one range of wavelengths of light emanating from the IPL source when activated; the band pass filter permits transmission of light from the IPL source when activated in the range of about 560nm to about 690nm; and, the IPL with the band pass filter provides equivalent cosmetic treatment as a laser with an operating wavelength of 595nm.
  • IPL intense pulsed light
  • a device for the cosmetic treatment of vascular lesions on skin tissue wherein the device is an equivalent of a laser having an operating wavelength of 755nm includes an intense pulsed light (IPL) source, the IPL source being activatable; a band pass filter which blocks substantially all but one range of wavelengths of light emanating from the IPL source when activated; the band pass filter permits transmission of light from the IPL source when activated in the range of about 700nm to about 800nm; and, the IPL with the band pass filter provides equivalent cosmetic treatment as a laser with an operating wavelength of 755nm.
  • IPL intense pulsed light
  • Fig. 1 graphically illustrates absorption of blood by light of various wavelengths.
  • Fig. 2 illustrates by a table the absorbent coefficients shown in Fig. 1
  • Fig. 3 graphically illustrates absorption of melanin by light in various
  • Fig. 4 illustrates in a table the absorbent coefficients shown in Fig. 3.
  • Fig. 5 illustrates graphically the ratio of the absorption coefficient of light in melanin over blood as a function of wavelength.
  • Fig. 6 illustrates graphically penetration depths of light into tissue at various wavelengths.
  • Fig. 7 illustrates graphically at different wavelengths the relative efficiency of IPL light sources.
  • Figs. 8 and 9 illustrate in tabular form typical numerical values of optical absorption at different wavelengths for different chromophores.
  • the absorption coefficient of light in tissue or chromophore is a function of wavelength.
  • Fig. 1 shown is a graph of light absorption values in whole blood as a function of wavelength for a "532 laser filter” in “solid lines” and a “Dye laser filter” in “dashed lines”.
  • the blood is assumed to consist of about 70% oxyhemoglobin and 30% deoxyhemoglobin on the average. It can be seen that the absorption level varies with the wavelength.
  • Fig. 2 shows a table containing selected numerical values derived from the graph of Fig. 1.
  • Fig. 3 shows a graph of the absorption values of light in melanin as a function of wavelength
  • Fig. 4 provides selected numerical values derived from the graph of Fig.3.
  • Figs 8 and 9 list typical numerical values of optical absorption at different wavelengths for different chromophores. Average absorption calculations which will be given as examples below are based on these numerical values.
  • a band pass filter for an IPL system may be provided in the range of 525 to 585 nm, as indicated in Fig. 1 as "532 laser filter" for vascular lesion treatment and as indicated in Fig. 9 which shows an example of a range of wavelengths which can be chosen to provide an equivalent averaged absorption coefficient as provided by the laser.
  • the average absorption coefficient referring to all wavelengths in this range in blood, is equal to the 232 1/cm which characterizes the 532 KTP laser absorbance in blood.
  • an IPL system having such a band pass filter would be expected to have a similar tissue interaction on skin as would the 532nm laser and may be as effective in the treatment of vascular lesions as a 532nm laser.
  • a dye laser which has a wavelength of about 595 nm has an absorption coefficient in the blood of about 60 1/cm.
  • the average absorption coefficient value of the band pass filter between 560nm and 690 nm will have the same average absorption coefficient in blood as a dye laser and therefore, according to this aspect of the invention, an IPL system with a band pass filter of 560nm to 690nm, "dye laser filter" as may be seen marked in Fig. 2 as such, may be provided for the treatment of vascular lesions.
  • an alexandrine laser (755nm) has an absorption coefficient of about 172 1/cm in melanin, as may be seen in Fig. 3.
  • a band pass filter from, for example, 700nm to 800nm passes a light spectrum which has, on the average, an absorption coefficient in melanin of 173 1/cm and therefore, according to this aspect of the present invention, an IPL system having a band pass filter between 700 nm to 800 nm is provided as an equivalent to an Alexandrite laser and called herein an "Alexandrite laser filter".
  • a band pass filter which passes a light spectrum from 675nm to 900nm may provide similar results.
  • Fig. 8 is a table with examples of ranges of wavelengths which can be chosen to provide, in an IPL device, an equivalent averaged absorption coefficient as the laser Alexandrite.
  • Such an IPL system may be deemed to be characterized with the same or very similar clinical effects as an Alexandrite laser for the treatment of pigmented lesions.
  • an IPL system having an IPL handpiece which has a permanent embedded filter which is configured to hold a band pass filter which delivers a spectrum of light which has an average absorption coefficient which is about similar to the absorption coefficient of one of the known laser wavelengths, such as for example KTP, 532nm, pulsed dye laser (PDL) 585nm-595nm, Alexandrite 755nm, diode laser 800-8 lOnm and Nd:YAG 532, Ruby 694nm or l,064nm and more.
  • PDL pulsed dye laser
  • an IPL system with an IPL handpiece may be configured to accept different filters, each in accordance with the present invention, so that a single handpiece may interchangeably deliver light spectrums which have average absorption coefficients on a target tissue or chromophore similar to those of equivalent known lasers.
  • the average calculation of a series of absorption values associated with a certain light spectrum which is passed through a band pass filter as described above, can be made in different ways.
  • the calculation of the average was a basic arithmetic average calculation in which the "weight" of each wavelength is similar.
  • the penetration depth of light into a tissue varies and is also a function of wavelength. Therefore, according to another aspect of the invention, the average absorption coefficient of a spectrum of light passed through a band pass filter in accordance with the present invention may be calculated based on a weighted average calculation.
  • an IPL system having an IPL band pass filter which is configured to deliver a spectrum of light which has an average absorption coefficient of a target tissue or chromophore which is similar to the absorption coefficient of a known laser at a predefined depth in the skin.
  • an Alexandrite laser of 755nm has an absorption value of an about 172 1/cm in melanin, as can be seen in Fig. 4.
  • a spectrum of light which on the average will have a similar absorption in melanin as the Alexandrite laser may be a band pass filter of 700nm to 800nm.
  • different band pass filters may also, on the average, produce a spectrum with an averaged absorption coefficient similar to an Alexandrite laser, for example, a band pass filter of 725 nm to 775 nm.
  • a critical energy threshold also preferably is reached in order to achieve a required clinical effect. Therefore, a band pass filter should be chosen, based on the lamp performances and intensity, to not only deliver a spectrum having an average light absorption in a target tissue or chromophore similar to that of a known laser but also to deliver at least the threshold energy to achieve a clinical effect.
  • an Alexandrite laser filter for pigmented lesion which aims to target melanin deeper in the skin due to the shift toward mid-infrared, may need to deliver a slightly different light spectrum shifted toward blue, in order to keep the average absorption value of the delivered spectrum around the 172 1/cm + at this deeper location.
  • the energy emitted from a lamp is also a function of wavelength.
  • the efficiency of the lamp is different and therefore a different amount of energy is irradiated and delivered Therefore, as mentioned above, a weighted average calculation may be performed in order to compensate for uneven energy distribution of the lamp.
  • An IPL system and an appropriate band pass filter which is configured to deliver a light spectrum which on a weighted average basis has an absorption coefficient value in the skin or anywhere inside the skin which is similar to the absorption coefficient value of a known laser in a target tissue or chromophore is also an aspect of the present invention.
  • FIG. 5 shows the ratio of the absorption coefficient of light in melanin over blood as a function of the wavelength.
  • the band pass filter of the present invention may be configured to pass a spectrum of wavelengths in which the ratio of the absorption of light in melanin over the absorption of light in blood is at least above 10 1/cm. A ratio higher than 10 1/cm will be expected to produce good selectivity for the treatment of pigmented lesion.
  • an IPL system may be configured to deliver a light spectrum having a ratio larger than 20 1/cm, larger than 30 1/cm, larger than 40 1/cm or larger than 50 1/cm to further enhance selectivity.
  • a lamp having a high degree of brightness is configured to deliver high energy fluences and therefore, even with the use of a relatively narrow band pass filters, a threshold energy sufficient to produce a clinical effect will be achieved.
  • One example of a suitable flash lamp for practicing the present invention may be that flashlamp structure as described in US Provisional Application Serial No.

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Abstract

La présente invention concerne un procédé cosmétique de photothérapie de tissus cutanés, qui comprend : la fourniture d'une source de lumière pulsée intense (IPL) ; l'intercalation d'un filtre passe-bande entre la source IPL et le tissu cutané ; le filtre passe-bande laissant passer la lumière dans une plage sélectionnée de longueurs d'onde avec un coefficient d'absorption moyen équivalent à celui d'une source de lumière laser sélectionnée ; le procédé comprend l'activation de la source IPL et l'application de celle-ci au tissu cutané, la lumière filtrée atteignant le tissu cutané produisant un traitement équivalent à celui de la source de lumière laser sélectionnée.
PCT/US2017/038781 2016-06-24 2017-06-22 Traitements sélectifs de la peau utilisant des dispositifs à lumière pulsée intense équivalente au laser WO2017223331A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
CN201780038674.2A CN109788946B (zh) 2016-06-24 2017-06-22 利用激光等效强脉冲光装置的选择性皮肤处理
IL303752A IL303752A (en) 2016-06-24 2017-06-22 Selective skin treatments utilizing laser-equivalent intense pulsed light devices
IL263143A IL263143B2 (en) 2016-06-24 2017-06-22 Selective skin treatments utilizing laser-equivalent intense pulsed light devices
EP17816217.8A EP3474762A4 (fr) 2016-06-24 2017-06-22 Traitements sélectifs de la peau utilisant des dispositifs à lumière pulsée intense équivalente au laser
CA3026197A CA3026197A1 (fr) 2016-06-24 2017-06-22 Traitements selectifs de la peau utilisant des dispositifs a lumiere pulsee intense equivalente au laser
CN202310077226.0A CN115998417A (zh) 2016-06-24 2017-06-22 利用激光等效强脉冲光装置的选择性皮肤处理
US17/836,160 US11813474B2 (en) 2016-06-24 2022-06-09 Cosmetic method and apparatus for selecting an IPL light source having a band pass filter equivalent to a specified wavelength laser light source for providing cosmetic treatment of skin tissue

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662354187P 2016-06-24 2016-06-24
US62/354,187 2016-06-24

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US16/221,545 Continuation US20200188687A1 (en) 2016-06-24 2018-12-16 Selective skin treatments utilizing laser-equivalent intense pulsed light devices

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WO2017223331A1 true WO2017223331A1 (fr) 2017-12-28

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EP (1) EP3474762A4 (fr)
CN (2) CN115998417A (fr)
CA (1) CA3026197A1 (fr)
IL (2) IL303752A (fr)
WO (1) WO2017223331A1 (fr)

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IL263143A (en) 2018-12-31
CN115998417A (zh) 2023-04-25
IL303752A (en) 2023-08-01
EP3474762A1 (fr) 2019-05-01
CA3026197A1 (fr) 2017-12-28
IL263143B1 (en) 2023-07-01
EP3474762A4 (fr) 2019-08-07
CN109788946A (zh) 2019-05-21
IL263143B2 (en) 2023-11-01

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