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WO2008052350A1 - Thérapie photodynamique pour le traitement de l'hidradenitis suppurativa - Google Patents

Thérapie photodynamique pour le traitement de l'hidradenitis suppurativa Download PDF

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Publication number
WO2008052350A1
WO2008052350A1 PCT/CA2007/001971 CA2007001971W WO2008052350A1 WO 2008052350 A1 WO2008052350 A1 WO 2008052350A1 CA 2007001971 W CA2007001971 W CA 2007001971W WO 2008052350 A1 WO2008052350 A1 WO 2008052350A1
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WIPO (PCT)
Prior art keywords
photosensitizer
lesions
subject
skin
tissue
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PCT/CA2007/001971
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English (en)
Inventor
Jing-Song Tao
David W.C. Hunt
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Qlt Inc.
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Publication of WO2008052350A1 publication Critical patent/WO2008052350A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/409—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having four such rings, e.g. porphine derivatives, bilirubin, biliverdine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0061—5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
    • 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
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • 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
    • 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
    • A61B2018/00458—Deeper parts of the skin, e.g. treatment of vascular disorders or port wine stains

Definitions

  • the present invention relates to a method of treating Hidradenitis Suppurativa (HS) with photodynamic therapy (PDT).
  • HS Hidradenitis Suppurativa
  • PDT photodynamic therapy
  • the use of PDT and systemically administered 0 photosensitizers for treating HS is disclosed.
  • Hidradenitis Suppurativa is a chronically relapsing inflammatory skin disease that affects an estimated 1% of the population. HS is characterized by recurrent painful nodules or abscesses, scarring, sinus tracts and recurrent odious discharge. Pain is a major
  • the disease also called acne inversa
  • the disease is characterized by large, deep lesions that are generally located in non-facial regions. The main locations are in the axillae, perineum and groin. Less commonly, lesions may occur in the perianal region, inframammary region, abdominal folds, genitalia, buttocks and neck.
  • HS patients suffer an average of 2-5 lesions per month per patient, with frequent recurrence and scar formation as
  • HS patients heal. Patients may present with single or multiple lesions in one area, or with lesions in many areas. In severe cases, patients may have large, recurrent, draining lesions that never completely heal. HS patients experience a lower quality of life than in any other dermatological disease studied.
  • HS morbidity and disabling nature of the disease.
  • the disease is a relatively common, affecting an estimated 1% of the population.
  • HS is more commonly found in women than in men (2.5-5: 1).
  • the average age of onset is approximately 20, and in women, the condition subsides after menopause.
  • the disease is highly chronic, with an average duration of 18 years.
  • HS is not contagious, and it is not sexually transmissible.
  • HS is classified as a follicular disorder of the skin under the World Health Organization's (WHO's) International Classification of Diseases 10 (ICD-10).
  • WHO's World Health Organization's
  • ICD-10 International Classification of Diseases 10
  • the pathogenesis of HS is believed to involve inflammation of the pilosebaceous units, which are composed of hair follicles and associated sebaceous and apocrine glands.
  • the proposed early pathogenesis of HS involves hyperproliferation of follicular lining keratinocytes, leading to follicular inflammation, enlargement and blockage.
  • the hyperproliferation of follicular keratinocytes is thought to be stimulated by androgen.
  • Stage I disease is characterized by formation of one or more isolated abscesses, with no scarring or sinus involvement.
  • stage II recurrent abscesses with tract formation and cicatrisation occur. Patients may present with single or multiple widely separated lesions.
  • Stage III is characterized by diffuse or near-diffuse involvement, and may involve multiple interconnected tracts and abscesses across an entire area of the body. Inflammation and chronic discharge may also appear.
  • stage I disease Current treatment options for stage I disease include oral and topical antibiotics, anti- androgens, retinoids, and immunosuppressive agents, as well as oral, topical and intralesional injection of steroids. These treatments frequently show very limited benefit, and are only useful for stage I disease. Pharmacotherapy does not prevent disease progression.
  • stage II disease requires destruction or elimination of the active chronic loci.
  • Treatment of stage III disease requires total excision of the entire disease region, frequently requiring subsequent skin graft. Early surgical intervention by wide local excision is advised at the earliest recognized stage.
  • TNF-alpha tumor necrosis factor alpha
  • Moul et al. reported the treatment of a patient suffering from severe HS with the anti-TNF-alpha monoclonal antibody, adalimumab (Humira ; Abbott Laboratories, Abbott Park, IL), consisting of 40 mg subcutaneous injections every other week. The patient showed significant improvement and resolution of pain after 1 month of treatment, with continued improvement at a 4 month follow up visit with the biweekly dosing.
  • adalimumab Humira ; Abbott Laboratories, Abbott Park, IL
  • Photodynamic therapy involves delivery of a photosensitive agent to a target tissue and activation of that agent with an appropriate energy source.
  • PDT involves concentrating a photosensitizing agent in a target tissue, then photoactivating the agent by irradiation with a device which includes a light source providing light at a particular wavelength and power level.
  • the agents administered for PDT are commonly known as photosensitizers (PS) due to their inherent ability to absorb photons of light and transfer that energy to oxygen which then converts to a cytotoxic or cytostatic species.
  • PSD photosensitizers
  • the photoactivating device employed for PDT usually comprises a monochromatic light source such as a laser.
  • Clinical trials have been conducted testing PDT as a potential therapy for various indications, including squamous cell carcinoma, basal cell carcinoma, actinic keratosis, age- related macular degeneration, and Barrett's esophagus.
  • PDT may be an effective treatment in many other indications.
  • U.S. Patent No. 5,095,030 (Levy et al.) which lists typical indications as including destruction of solid tumors, dissolution of plaques in blood vessels, treatment of topical indications such as acne, athletes' foot, warts, papilloma, psoriasis, and the treatment of biological products such as blood for infectious agents.
  • U.S. Patent No. 6,897,238 (Anderson et al.) which discloses PDT with topical 5-aminolevulinic acid (ALA) for the treatment of sebaceous gland disorders, including acne vulgaris.
  • ALA 5-aminolevulinic acid
  • Strauss et al. did not observe clinical improvement in HS patients treated with topical ALA and red light PDT.
  • one patient was treated using a 633 nM diode laser, while three others were treated using a broadband red light source in the 570-670 nM range. All four patients complained of burning and stinging following each treatment, and two patients did not complete the study. None of the four patients showed significant improvement in regional HS scores at an 8 week follow-up visit, and two patients showed deterioration.
  • Strauss et al. note that the results of the Gold study are surprising, given that blue light penetrates to a depth of only around 1-2 mm, while HS involves deeper lesions. The authors note that the short exposure time to ALA (30 minutes) raises questions as to whether sufficient ALA could be absorbed to be therapeutically effective. Strauss et al., Brit. J. Dermatol. 2005; 152:803-804.
  • the present invention relates to the use photodynamic methods for treating and/or preventing hidradenitis suppurativa (HS).
  • the present methods involve: (i) systemically administering a photosensitizer to a subject having HS; and (ii) exposing the affected tissue to energy of a wavelength capable of activating the photosensitizer (PS).
  • PS photosensitizer
  • the PS is a lipophilic and/or hydrophobic PS.
  • Photodynamic therapy may represent a safer and more efficacious approach to treating HS than existing pharmacological or procedural therapies, due to its selectivity toward the pilosebaceous units in skin. Such an approach may be capable of changing the course of disease when given to patients with early stage disease.
  • a method to treat, reduce or inhibit hidradenitis suppurativa (HS) lesions or peri-lesions with photodynamic therapy comprising systemically administering a pharmaceutical composition comprising photosensitizer to a subject in need thereof; and exposing of the affected tissue in said subject to energy of a wavelength capable of activating the photosensitizer after waiting an appropriate period of time to allow accumulation of the photosensitizer in the affected tissue.
  • HS hidradenitis suppurativa
  • a method to treat, reduce or inhibit hidradenitis suppurativa (HS) lesions or peri-lesions with repeated photodynamic therapy comprising (i) systemically administering a photosensitizer to a subject in need thereof; (ii) exposing the affected tissue in said subject to energy of a wavelength capable of activating the photosensitizer after waiting an appropriate period of time to allow accumulation of the photosensitizer in the affected tissue; and (iii) repeating steps (i) and (ii) at least once.
  • HS hidradenitis suppurativa
  • a method to prevent hidradenitis suppurativa (HS) lesions or recurrence of HS lesions comprising systemically administering a photosensitizer to a subject at risk of developing HS lesions; and exposing of the affected tissue in said subject to energy of a wavelength capable of activating the photosensitizer after waiting an appropriate period of time to allow accumulation of the photosensitizer in the affected tissue.
  • the subject has previously undergone an ablative or surgical procedure for HS.
  • (HS) lesions or peri-lesions with repeated photodynamic therapy comprising (i) systemically administering a photosensitizer to a subject in need thereof; (ii) exposing the tissue at risk in said subject to energy of a wavelength capable of activating the photosensitizer after waiting an appropriate period of time to allow accumulation of the photosensitizer in the tissue at risk; and (iii) repeating steps (i) and (ii) at least once.
  • the use of a photosensitizer for the treatment or prevention of hidradenitis suppurativa (HS) lesions or peri-lesions as described herein or the use of a photosensitizer for the manufacture of a medicament for the treatment or prevention of hidradenitis suppurativa (HS) lesions or peri-lesions as described herein also is contemplated.
  • the pharmaceutical composition is formulated with an excipient or carrier capable of directing said photosensitizer to lipid rich pilosebaceous units.
  • the photosensitizer can be administered intravenously or orally.
  • the photosensitizer is a lipophilic and/or hydrophobic photosensitizers.
  • the photosensitizer is selected from the group consisting of 5-aminolevulinic acid and derivatives thereof, 5-aminolevulinic acid esters and derivatives thereof, porphyrins and derivatives thereof, methylene blue and derivatives thereof, bacteriochlorophyll and derivatives thereof, and combinations thereof.
  • the photosensitizer also can be selected from the group consisting of 5-aminolevulinic acid, 5-aminolevulinic acid esters, chlorins, bacteriochlorins, isobacteriochlorins, phthalocyanine, naphthalocyanines, pyropheophorbides, sapphyrins, texaphyrins, tetrahydrochlorins, purpurins, porphycenes, phenothiaziniums, bacteriochlorophyll, bacteriochlorophyll derivatives, pro-porphyrins, porphyrins, green porphyrins, and combinations thereof.
  • the photosensitizer is selected from the group consisting of verteporfin, the benzoporphyrin derivative mono-acid (BPDMA), lemuteporfin, B3, and combinations thereof.
  • BPDMA benzoporphyrin derivative mono-acid
  • the photosensitizer also can be conjugated to a targeting ligand.
  • the method or use further comprises the administration of one or more non-photodynamic therapies for HS.
  • Such therapies can include antibiotics, anti- androgens, retinoids, immunosuppressive agents, steroids, anti-TNF- ⁇ antibodies, cryotherapy, laser ablation, surgery, and combinations thereof.
  • the photosensitizer also can be conjugated to a targeting ligand.
  • Figures l(a)-(c) show skin fluorescence profiles for female Balb/c mice administered 0.1 ml of 5% dextrose in water (5DW) intravenously 24 hours before. Frozen skin cross- sections were prepared, examined by fluorescence microscopy and images captured using a digital camera system. Sections are oriented with the outer part of the skin towards the top of each image. Individual mouse identification numbers are given.
  • Figures 2(a)-(i) show fluorescence profiles for female Balb/c mice administered LFI intravenously at 10 mg/kg 1, 3 or 24 hours before. Frozen sections were prepared, examined by fluorescence microscopy and images captured by a digital camera system. Sections are oriented with the outer part of the skin towards the top of each image. Mouse identification numbers are given.
  • Figures 3(a)-(i) show skin fluorescence profiles for female Balb/c mice administered LFI intravenously at 25 mg/kg 1, 3 or 24 hours before. Frozen sections were prepared, examined by fluorescence microscopy and images captured by a digital camera system. Sections are oriented with the outer part of the skin towards the top of each image. Mouse identification numbers are given.
  • Figure 4 shows representative high-power fluorescence profile of a section prepared from a skin sample of a mouse (ME2416) given LFI intravenously at 25 mg/kg one hour previously. Cryo-sections were prepared, viewed by fluorescence microscopy and images captured by a digital camera system. Different skin structures are indicated by abbreviations: ad: adipose layer; hf: hair follicle; sg: sebaceous gland; sc: stratum corneum. Fluorescence is most prominent for sebaceous glands but also evident in the epithelial lining of hair follicles and subcutaneous adipose layer. The horizontal bar indicates the relative scale of the image.
  • Figures 5(a)-(e) show ear cross-section fluorescence profiles for samples obtained from adult male hamsters administered LFI (4 mg/kg) intravenously 1 hour before. Frozen sections were prepared, examined by fluorescence microscopy and images captured by a digital camera system. All section images were captured using the same camera exposure time (10 seconds). Sebaceous gland structures are evident by their stronger fluorescence signature within ear sections prepared from LFI-injected hamsters. Sections are oriented with the dorsal ear surface towards the top of each image. Individual animal identification numbers are given.
  • Figure 6 shows the effect of PDT with systemically- administered LFI (1 mg/kg) on the status of Balb/c mouse sebaceous glands was evaluated (PDT study 3, ACF0699).
  • Animals were exposed to a red light dose of 50 or 100 J/cm 2 given either 45 or 60 minutes after LFI injection. Light intensity was 200 mW/cm 2 .
  • Control animals received 5DW and exposed to a red light dose of 100 J/cm 2 60 minutes later. Groups consisted of ten mice per group with five per group sacrificed on Days 3 and 7 post-PDT.
  • mice For LFI-injected mice exposed to a red light dose of 100 J/cm , several mice were lost to analysis For Group 3, three samples were subjected to analysis at 72 hours and for Group 5 mice four mice were available for sebaceous gland determinations at day 7. Mean total (H) and Oil Red O- positive (D) PSU counts with standard deviations as determined by the Reader (JT) for the 72 (first pair of bars) and 168 (second pair of bars) hour sampling times are shown.
  • Figures 7(a)-(c) show concentration of LFI fluorescence in sebaceous glands in mouse skin following LFI injection at 25 mg/kg. Rapid uptake and subsequent loss of lemuteporfin fluorescence over the time, associated with sebaceous gland epithelial cell lining is observed. Similar findings were observed with 10 mg/kg dose.
  • Figure 8 shows preferential retention of LFI in rat skin following 4 mg/kg IV bolus injection.
  • Figures 9(a)-(b) show preferential accumulation of LFI in sebaceous glands in a hamster ear model one hour post-injection of 5WD or LFI (4 mg/kg).
  • FIG 10 shows selective destruction of mouse sebaceous glands with PDT. Sebaceous gland status 72 hours post-PDT (5 mice/group) is shown. No appreciable skin photosensitivity reactions or histological signs of inflammation were produced.
  • Figure 11 shows the results of a mouse LFI-PDT study.
  • Mouse sebaceous gland counts at 72 hours and 7 days post-PDT are plotted for certain light dose/irradiation time combinations following injection of LFI (1 mg/kg). Sebaceous gland reductions were evident at 72 h post-PDT with certain combinations. PDT was generally well tolerated, and no skin photosensitivity reactions were produced.
  • the methods of the present invention involve the use of photodynamic therapy (PDT) to treat HS.
  • PDT photodynamic therapy
  • the methods involve the systemic administration of a photosensitizer to a subject having HS and subsequent exposure of the affected tissue to energy of a wavelength capable of activating the photosensitizer.
  • the methods can be used to treat active HS lesions, as well as skin containing peri-lesion structures with pathological changes that are responsible for developing HS lesions in the future.
  • the methods may be used to treat early stage disease or recurrent HS.
  • an appropriate period of time refers to the time necessary to allow the PS to selectively accumulate in the affected tissue. It will be understood that an “appropriate period of time” for a particular aspect may vary depending on the pharmacokinetic and pharmacodynamic profile of the PS, the dosage of energy used to activate the PS, and the desired therapeutic effect.
  • systemic administration refers to administration through either parenteral or enteral routes of administration. Accordingly, as defined herein “systemic administration” includes but is not limited to intravenous injection, intravenous infusion, intralesional injection, mucosal delivery, oral administration, or rectal administration of an appropriately formulated PS.
  • hydrophobic photosensitizer refers to photosensitizers that repel water, have a tendency not to combine with water, or are incapable of being substantially dissolved in water.
  • lipophilic photosensitizer refers to photosensitizers that have an affinity for, tend to combine with, or are capable of substantially dissolving in, lipids.
  • hydrophobicity is the LogP value. In general, substances having a LogP of 0 or greater are thought to be hydrophobic while those with a negative LogP value are thought to be hydrophilic.
  • hydrophobic or lipophilic photosensitizer composition refer to the composition as it is administered to the subject. Therefore, the term encompasses both hydrophobic and lipophilic photosensitizers, and hydrophilic photosensitizers that are formulated such that the composition as it is administered is hydrophobic or lipophilic, as defined above.
  • the term “lesion” refers to active HS lesions. Such lesions are typically characterized by painful and deep-seated inflammatory nodules with induration, frequently with abscess formation, draining and malodorous discharge.
  • the term “affected tissue” refers to skin displaying active HS lesions, as well as apparently "normal” skin which may contain peri-lesions, i.e. pilosebaceous structures with pathological changes that are responsible for developing HS lesions in the future.
  • peri-lesion refers to areas of skin bordering active lesions that may contain pathological changes to the underlying pilosebaceous units. Such peri- lesions are believed to be responsible to developing active HS lesions in the future. The f ailure of conventional HS therapies and procedures to effectively treat these peri-lesion structures is believed to be a major cause of recurrence in HS.
  • tissue susceptible to developing HS refers to tissue which is located in the areas of the body most frequently affected by HS, including but not limited to axillae, perineum and groin. Susceptible tissue also includes tissue adjacent to active lesions or peri-lesions.
  • PDT using a systemically administered PS may offer advantages for treating HS.
  • the large, deep lesions that are characteristic of HS may not be accessible to topical agents.
  • Topical delivery of drugs into the pilosebaceous units of humans is challenging due to the skin thickness and sebaceous gland size of human subjects.
  • treatment with topical antibiotics or retinoid agents alone has shown limited efficacy in treating HS.
  • topical delivery of ALA and red-light PDT was likewise unsuccessful in treating HS lesions. Strauss et al., Brit. J. Dermatol. 2005; 152:803-804.
  • the present invention is based, at least in part, on the discovery that following systemic administration, lipophilic and/or hydrophobic PS preferentially accumulate and are retained in the pilosebaceous units, which are lipid rich skin appendages that include the hair follicles, sebaceous and apocrine glands. Subsequent exposure to energy of a wavelength capable of activating the photosensitizer results in selective ablation of pilosebaceous units in the treated lesion without causing significant skin damage. It is believed that selective accumulation and retention of the PS in the pilosebaceous unit reduces the risk of potential side effects, such as erythema, edema, pain, burning and itching.
  • a photosensitizer may be selectively accumulated and/or retained in certain body tissues or cell types. Tissue-selective accumulation or retention of a photosensitizer may be due a number of factors including the metabolic state of the cell/tissue, the outer membrane composition of the cell, and/or the binding of the photosensitizer to plasma proteins such as low density lipoproteins (LDL) which are specifically taken up by cell-surface receptors expressed by proliferative cell types.
  • LDL low density lipoproteins
  • Selective accumulation of a photosensitizer may be defined as a higher level of the compound of interest in certain body regions in relation to other tissue types in the immediate vicinity or distal sites.
  • the terms "selective accumulation” or “selectively accumulate” refer to the tendency of lipophilic and/or hydrophobic PS to be preferentially acquired by lipid-rich cells, such as basal and differentiated sebocytes and apocrine secreting cells and/or preferentially accumulated in the lumens of pilosebaceous structures, due to their affinity to lipids or other lipophilic contents within the hair follicles, sebaceous and apocrine glands.
  • Tissue selective photosensitizer retention may also be revealed by evaluating tissues at increasing times following photosensitizer administration. Although equivalent tissue levels, as determined by fluorescence or radioactive tracer studies, may be present at early times following administration, a photosensitizer may be released from certain tissues at faster rates than from other tissues. For the skin, this feature may be indicated by greater photosensitizer fluorescence density for sebaceous glands relative to the surrounding dermis, the inter-follicular epidermis, vasculature, underlying adipose and muscle layers. Such concentration differences may permit tissue-selective PDT effects to be achieved when activating light is applied since sufficient levels of the photosensitizer remain in the target tissue.
  • the terms “selective retention” or “selectively retained” refer to the tendency of lipophilic and/or hydrophobic PS to be bound to pilosebaceous cells or the lipid or lipophilic contents within the pilosebaceous units over an extended period of time that is longer than the time required to clear the PS from other parts of the skin, including skin structures such as the microvasculature, epithelium, and other cutaneous and subcutaneous structures. Selective accumulation and/or retention of hydrophobic and/or lipophilic PS in the pilosebaceous units allow expansion of the treatment field using PDT to include both active lesions and peri-lesion structures.
  • the present invention relates to a photodynamic method of preventing, treating, inhibiting or reducing lesions and/or peri-lesions in a subject having HS.
  • the method involves exposing the affected tissue to energy of a wavelength capable of activating a photosensitizer, wherein the PS was systemically administered to the subject.
  • the present invention relates to a photodynamic method of preventing, treating, inhibiting or reducing lesions and/or peri-lesions in a subject having HS involving exposing the affected tissue to energy of a wavelength capable of activating a systemically administered photosensitizer after waiting an appropriate period of time to allow the PS to accumulate in the affected tissue.
  • the PS is selected from the group consisting of verteporfin, lemuteporfin or combinations thereof.
  • the present method involves: (i) systemically administering a hydrophobic and/or lipophilic photosensitizer composition to a subject having HS; and (ii) exposing the affected tissue to energy of a wavelength capable of activating the photosensitizer, wherein the activation energy is at least in part supplied by light emitting diodes (LED).
  • LED are preferably arrayed in a manner that somewhat follows the contours of the skin to be treated.
  • a preferred arrangement is multiple flat panels of LED's that are moveable so that they can be positioned appropriately.
  • PDT can be combined with Blue-light Phototherapy to give extra efficacy benefits. Therefore, one embodiment of this aspect of the invention involves the activation energy being delivered by an LED devise that supplies both red (e.g. 600-75OnM) and blue light (e.g. 390-45OnM).
  • an LED devise that supplies both red (e.g. 600-75OnM) and blue light (e.g. 390-45OnM).
  • red e.g. 600-75OnM
  • blue light e.g. 390-45OnM
  • the methods of the invention may be used alone or in combination with other therapies for HS.
  • Known therapies include but are not limited to pharmacotherapy (using antibiotics, anti-androgens, retinoids, immunosuppressive agents, steroids and anti-TNF- alpha antibodies), cryotherapy, laser ablation, surgery, and combinations thereof.
  • PDT using a systemically administered PS may be combined with simultaneous administration of a retinoid or anti-androgen at the site of the lesion.
  • PDT using a systemically administered PS may be combined with intralesional injection of a steroid or anti-androgen.
  • PDT with a systemically administered PS may be used to treat peri-lesion structures, thereby preventing progression of the peri-lesion into an active lesion.
  • PDT with a systemically administered PS may be used to treat a subject who had previously undergone an ablative or surgical procedure, thereby preventing recurrence of the lesion.
  • the photosensitizer herein is delivered systemically.
  • Systemic delivery allows accumulation and retention of the PS in the pilosebaceous units of the affected tissues, which include active HS lesions as well as peri-lesions in surrounding skin.
  • Any suitable photosensitizing agent or mixture of agents may be used herein.
  • these agents will absorb radiation in the range of from 400 nm to 900 run preferably from 450nm to 750nm, more preferably 500nm to 700nm.
  • photosensitizer or “photosensitizing agent” means a chemical compound that absorbs electromagnetic radiation, most commonly in the visible spectrum, and releases it as energy, most commonly as reactive oxygen species and/or as thermal energy.
  • the compound is nontoxic to humans or is capable of being formulated in a nontoxic composition.
  • the chemical compound in its photodegraded form is also nontoxic.
  • a non-exhaustive list of photosensitive chemicals may be found in Kreimer- Birnbaum, Sem. Hematol. 26: 157-73, 1989 and in Redmond and Garnlin, Photochem. Photobiol. 70 (4): 39 1-475 (1999) both of which are incorporated herein by reference.
  • the photosensitizer composition used in the present methods is lipophilic and/or hydrophobic. Photosensitizers that strongly absorb light with extinction coefficients > 10,000 M " 1 Cm "1 are preferred.
  • photosensitizers including, but not limited to, pro-drugs such as the pro-porphyrin 5-aminolevulinic acid (ALA) and derivatives thereof, porphyrins and porphyrin derivatives (e.g. chlorins, bacteriochlorins, isobacteriochlorins), methylene blue derivatives, phthalocyanine and naphthalocyanines and other tetra- and polymacrocyclic compounds, and related compounds (e.g. pyropheophorbides, sapphyrins and texaphyrins) and metal complexes (such as, but not limited by, tin, aluminum, zinc, lutetium).
  • pro-drugs such as the pro-porphyrin 5-aminolevulinic acid (ALA) and derivatives thereof, porphyrins and porphyrin derivatives (e.g. chlorins, bacteriochlorins, isobacteriochlorins), methylene blue derivatives,
  • Tetrahydrochlorins, purpurins, porphycenes, and phenothiaziniums are also within the scope of the invention.
  • Other suitable photosensitizers include bacteriochlorophyll derivatives such as those described in WO-A-97/19081, WO-A- 99/45382 and WO-A-01/40232.
  • a preferred bacteriochlorophyll is palladium- bacteriopheophorbide WST09 (TookadTM ).
  • the photosensitizers are selected from pro-porphyrins, porphyrins, and mixtures thereof.
  • pro-drugs include aminolevulinic acid such as LevulanTM and aminolevulinic acid esters such as described in WO-A-02/10120 and available as MetvixTM, HexvixTM and BenzvixTM.
  • aminolevulinic acid such as LevulanTM
  • aminolevulinic acid esters such as described in WO-A-02/10120 and available as MetvixTM, HexvixTM and BenzvixTM.
  • di-hydro or tetra-hydro porphyrins are described in EP-A-337,601 or WO-A-01/66550 and available as FoscanTM (temoporfin). Combinations of two or more photosensitizers may be used in the practice of the invention.
  • the photosensitizers are selected from those which photobleach upon exposure to activation energy.
  • green porphyrins A particularly potent group of photosensitizers is known as green porphyrins, which are described in detail in U.S. Patent No. 5,171,749 (incorporated herein by reference).
  • Gp green porphyrins
  • BPDs benzoporphyrin derivatives
  • green porphyrins are selected from a group of tetrapyrrolic porphyrin derivatives obtained by Diels-Alder reactions of acetylene derivatives with protoporphyrin under conditions that promote reaction at only one of the two available conjugated, nonaromatic diene structures present in the protoporphyrin-EX ring systems (rings A and B).
  • Metallated forms of a Gp in which a metal cation replaces one or two hydrogens in the center of the ring system, may also be used in the practice of the invention.
  • the preparation of the green porphyrin compounds useful in this invention is described in detail in U.S. Patent No. 5,095,030 (incorporated herein by reference).
  • Preferred green porphyrins include benzoporphyrin derivative diester diacid (BPD-DA), mono-acid ring A (BPD-MA), mono- acid ring B (BPD-NIB), or mixtures thereof. These compounds absorb light at about 692nm wavelength which has good tissue penetration properties.
  • BPD- MA and BPD-MB may be homogeneous, in which only the C ring carbalkoxyethyl or only the D ring carbalkoxyethyl would be hydrolyzed, or may be mixtures of the C and D ring substituent hydrolyzates.
  • BPD B -ring derivatives may also be used in the present invention. These derivatives have the following general formula:
  • Preferred photosensitizers include verteporfin, the benzoporphyrin derivative mono- acid (BPDMA), lemuteporfin (QLT0074 as set forth in U.S. Pat. No. 5,929,105 referred to therein as AEA6) and B3 (as set forth in U.S. Pat. No. 5,990,149), and combinations thereof.
  • BPDMA benzoporphyrin derivative mono- acid
  • AEA6 lemuteporfin
  • B3 as set forth in U.S. Pat. No. 5,990,149
  • the photosensitizers may be conjugated to various ligands to facilitate targeting.
  • ligands include receptor- specific peptides and/or ligands as well as immunoglobulins and fragments thereof.
  • Preferred ligands include antibodies in general and monoclonal antibodies, as well as immunologically reactive fragments of both.
  • Dimeric forms of the green porphyrin and dimeric or multimeric forms of green porphyrin/porphyrin combinations can be used.
  • the dimers and oligomeric compounds of the invention can be prepared using reactions analogous to those for dimerization and oligomerization of porphyrins per se.
  • the green porphyrins or green porphyrin/porphyrin linkages can be made directly, or porphyrins may be coupled, followed by a Diels- Alder reaction of either or both terminal porphyrins to convert them to the corresponding green porphyrins.
  • photosensitizers include, but are not limited to, green porphyrins disclosed in US Pat. Nos. 5,283,255, 4,920,143, 4,883,790, 5,095,030, and 5,171,749; and green porphyrin derivatives, discussed in US Pat. Nos. 5,880,145 and 5,990,149.
  • green porphyrins disclosed in US Pat. Nos. 5,283,255, 4,920,143, 4,883,790, 5,095,030, and 5,171,749
  • green porphyrin derivatives discussed in US Pat. Nos. 5,880,145 and 5,990,149.
  • the photosensitizer may be administered in any form suitable for systemic administration.
  • the photosensitizer may be systemically administered by means including, but not limited to intravenous infusion or injection, intralesional injection, mucosal delivery, oral and rectal routes of administration.
  • the photosensitizer may be used alone or as a component of a mixture.
  • the photosensitizers may be formulated into a variety of compositions. These compositions may comprise any component that is suitable for the intended purpose, such as conventional delivery vehicles and excipients including isotonising agents, pH regulators, solvents, solubilizers, dyes, gelling agents and thickeners and buffers and combinations thereof.
  • Pharmaceutical formulations suitable for use with the instant photosensitizers can be found, for instance, in Remington's Pharmaceutical Sciences (21st ed. 2005).
  • Preferred formulations herein comprise pharmaceutical excipients or carriers capable of directing the photosensitizer to lipid rich pilosebaceous units.
  • Suitable excipients for use with photosensitizers include water, saline, dextrose, glycerol and the like.
  • a preferred formulation involves reconstitution of a lipid based lyophilized PS with sterile distilled water. Subsequent dilution for dosing with 5% dextrose in water (5DW) allows preparation of a dose appropriate to the bodyweight of the human or animal subject.
  • Exemplary carriers capable of directing the photosensitizer to sebaceous units include those disclosed in U.S. Patent Nos. 6,074,666; 6,890,555; and 7,135,193.
  • the activation energy comprises a wavelength close to at least one of the absorption peaks of the photosensitizer. This wavelength differs for different photosensitizers.
  • BPD-MA has an absorption peak at 689nm and so, when
  • BPD-MA is the photosensitizer used, the wavelength of the activation energy is preferably is at or close to 689nm.
  • the photosensitizer ALA-methyl ester (available under the tradename Metvix) has an absorption peak at 635nm and so when this photosensitizer is used the activation energy is preferable at or close to 635nm.
  • ALA (available under the tradename Levulan) has an absorption peak at 417nm and at 630nm so when this photosensitizer is used the activation energy is preferable at or close to 417nm and/or 630nm.
  • the activation energy herein may be provided by any suitable means.
  • the activation energy is provided by a visible light source although it has been suggested that x- ray, ultraviolet, or ultrasound sources may be used.
  • Preferred sources include, but are not limited to, lasers, light emitting diodes (LED), incandescent lamps, arc lamps, standard fluorescent lamps, U.V. lamps, and combinations thereof. More preferred are light emitting diodes.
  • any convenient source of activation energy having a component of wavelengths that are absorbed by the photosensitizer may be used, for example, an operating room lamp, or any bright light source, including sunlight.
  • CureLightTM available from Photocure ASA, Oslo, Norway
  • BLU- UTM available from DUSA, Wilmington, MA, USA
  • PDT Laser available from Diomed, Andover, MA, USA
  • CeralasTM available from Biolitec AG, Jena, Germany
  • OmniluxPDTTM available from PhotoTherapeutics Ltd., Birmingham, UK
  • Q-Beam & Quanta-med Quantum Devices Inc., Barneveld, WI, USA.
  • the activation energy dose administered during the PDT treatment contemplated herein can vary as necessary.
  • the dosage of the light is about 25-100 J/cm 2 .
  • the total dose of the irradiation should generally not exceed 400 J/cm , preferably 200 J/cm , or more preferably not exceed 100 J/cm 2 .
  • Preferred doses can range between about 0.1 J/cm 2 to about 200 J/cm 2 , more preferably 1 J/cm 2 to about 100 J/cm 2 .
  • the intensity of the energy source should not exceed about 600mW/cm 2 .
  • Irradiances between about 0.1 and 400 mW/cm 2 are preferred. Even more preferably the irradiance is between 5 and 100 mW/cm 2 .
  • the irradiation lasts from about 10 seconds to about 4 hours, and preferably between about 5 minutes and 1 hour.
  • irradiation times of about 10, about 15, about 20, about 30, about 45, about 60, about 75, about 90, about 105, about 120, about 135, about 150, about 165 and about 180 minutes may be used.
  • the area to be treated have minimal hair coverage when the activation energy is applied. Therefore, if there is significant hair coverage of the area to be treated, it is preferred that the hair is cut short or shaved prior to activation energy application.
  • hair coverage can affect the activation energy dose that is delivered to the target area, especially when visible light wavelengths are used. Consequently, in order to more accurately deliver the correct does it is preferred that there be little or no hair coverage.
  • the shielding effect of the hair may be compensated for by changes to delivery of the activation energy.
  • the irradiation or light exposure used in the invention may be directed to a small or large area of the body depending on the lesion to be treated. Any part of the body may be treated but HS typically affects the axillae, perineum, and groin.
  • Treatment may be preceded with an assessment of the time of light exposure for the patient's minimal erythemal dose (MED) occurrence in order to avoid potential burning of the exposed skin.
  • the treatment may be repeated as many times as is necessary. If repeated, the treatment frequency may vary.
  • the treatments could be daily, every two days, twice weekly, weekly, every two weeks, twice monthly, every four weeks, monthly, every six weeks, every eight weeks, every two months, quarterly, twice annually, or annually, or other suitable time interval.
  • the treatment is not repeated more than once per week.
  • the treatment is repeated at least once every six months.
  • the total number of treatments can range from one to as many as required.
  • the total number of treatments in any 6 month period be from 1 to 12, more preferably from 1 to 6, even more preferably from 2 to 3.
  • the preferred time between treatments ranges from 1 week to 3 months.
  • the activation energy is administered within 24 hours of administration of the PS.
  • Preferred doses of energy are between 15 and 200 J/cm2. More preferred doses include 20, 40, 80, or 120 J/cm 2 . It will be understood that the appropriate dose of energy will depend on the time elapsed following administration of the PS, the rate and level of accumulation of PS in the affected tissue, as well as the rate of clearance from both affected and non-affected tissues.
  • a low dose of activation energy is administered 1-6 hours after systemic administration of the PS.
  • a high dose of activation energy is administered 12-24 hours following systemic administration of the PS.
  • Preferred photosensitizers are selected from verteporfin, lemuteporfin, or combinations thereof.
  • LFI Lemuteporfin for Injection
  • mice Female Balb/c mice (3 animals per group) of approximately 16 weeks of age received a single intravenous dose of LFI via a tail vein.
  • the LFI doses were 10 and 25 mg/kg.
  • Control animals received an intravenous injection of the delivery vehicle, 5% dextrose in water (5DW). The injection volume was 0.1 ml.
  • LFI- injected mice were either sacrificed 1, 3 or 24 hours after LFI administration.
  • the group of mice given vehicle alone was sacrificed 24 hours post-injection.
  • Treatment groups are summarized in Table 3. TABLE 3. Treatment Group Allocation
  • animals were euthanized by CO 2 asphyxiation with cervical dislocation. An area of flank skin was closely shaved with an electric razor. A full- thickness skin sample from this site was carefully excised and prepared for fluorescence analysis. Samples were placed in embedding medium, frozen on liquid nitrogen and then stored at -70°C until processed for histology.
  • Histological procedures were performed under light-reduced conditions. For sectioning, blocks were first trimmed until an entire skin cross-section was clearly visible. Two slides with four 8 ⁇ m-thick sections were cut with a cryostat and then cover-slipped with Faramount, an aqueous based acrylic mounting medium (Dakocytomation, Mississauga, Ontario). Slides were stored at 4 0 C in the dark until read on the fluorescence microscope.
  • an LFI dose of 10 mg/kg sebaceous glands were clearly marked by bright fluorescence with good consistency among the 3 animals treated in this manner ( Figures 2(a)-(i)).
  • lower sebaceous gland fluorescence was evident at 3 hours and approached control levels for skin sections prepared from mice 24 hours post-injection.
  • LFI Lemuteporfin for Injection
  • Histological procedures were performed under light-reduced conditions. For sectioning, blocks were first trimmed until an entire ear cross-section was clearly visible. Two slides with four 8 ⁇ m-thick sections were cut with a cryostat and then cover-slipped with Faramount, an aqueous based acrylic mounting medium (Dakocytomation, Mississauga, Ontario). Slides were stored at 4°C in the dark until read on the fluorescence microscope.
  • mice Normal female Balb/c mice of 8-12 weeks of age were used. Test groups consisted of 5-10 animals. Right flank skin was initially shaved and the 1.5-cm x 1.5-cm treatment site demarcated by tattoo marks on each corner of the square.
  • mice received a single intravenous dose of vehicle or LFI in a tail vein in a volume of 0.1 ml under subdued light conditions. After the injection, animals were kept under light-protected conditions. At different specified times following LFI injection, mice were immobilized by Isofluorane inhalation anesthesia for PDT. An aluminum foil cover was placed over the animal so that only 1.5-cm x 1.5-cm square demarcated area on the right flank was visible. The designated site was exposed to red (688-nm) light provided by a Biolitec® 100 Light Emitting Diode (Biolitec Inc.) with a Thermotek Treatment Head and Cooler delivered at an intensity of 50 or 200 mW/cm 2 . Once full recovery from anesthesia was confirmed, the mice were returned to their cages and regular housing conditions. Animals were monitored daily for general health and for potential skin photosensitivity reactions such as erythema, edema or necrosis.
  • red (688-nm) light provided by a Biolite
  • mice were sacrificed either 72 hours or 7 days after PDT. Following CO 2 euthanasia with cervical dislocation, full-thickness skin from within the tattoo points on the PDT-treated right flank was carefully excised. The upper half of these tissue squares were placed in a plastic mold filled with "Neg 50" cryo embedding medium and frozen on liquid nitrogen. The lower half was preserved in formol acetic alcohol for 18 hours. The tissue was transferred to 70% alcohol until processed to wax by a standard in-house protocol. Formalin-fixed samples were subsequently stained with standard reagents (e.g. hematoxylin and eosin) to assess general histological changes within the tissue.
  • standard reagents e.g. hematoxylin and eosin
  • frozen tissue samples were cut in 8 ⁇ m sections with a cryostat onto glass slides and immediately fixed in 10% buffered formalin. Three sets of 2 slides were cut from each block with the distance between sets of approximately 200 ⁇ m. One slide from each set was stained with Oil Red O and then cover-slipped with acrylic mounting medium and allowed to set.
  • Study ACF06-051 evaluated the effect of LFI at 1 mg/kg combined with red light doses of 2.5, 5, 10 or 25 J/cm delivered at a fluence rate of 50 mW/cm either one or two hours after LFI injection (Table 4). No change in sebaceous gland counts was observed for any treatment group. Minor histological changes within the skin were evident for animals treated with the higher red light doses at 1 hour post-LFI injection. These were characterized by modest increases in sebaceous gland size as well as inter-follicular and hair follicle epithelial layer thickness for skin samples prepared 72 hours post-PDT. These responses were suggestive of a minor stimulatory effect produced by PDT within the treatment area. Further, there was evidence of sebaceous gland disruption (granulation) in basal/mid-regions of glands with the highest light doses (10, 25 J/cm 2 ).
  • PDT study ACF06-072 used LFI doses of 1, 2.5 or 5 mg/kg combined with red light doses of 25 or 50 J/cm 2 given at an intensity of 50 mW/cm 2 (Table 5).
  • Necropsy evaluations revealed gastrointestinal tract damage. However, for PDT-treated animals given the lower LFI and /or light doses, little change in appearance of skin sub-structures was evident for skin samples obtained 72 hours post-PDT.
  • mice flank skin was exposed to red light doses of 50 or 100 J/cm 2 either 45 minutes or 1 hour following injection of LFI at 1 mg/kg (Table 6).
  • the red light intensity was 200 mW/cm 2 .
  • Two of ten animals in Group 3 and one of ten mice in Group 5 died two days after PDT. Necropsy evaluations indicated damage had been caused to internal organs immediately beneath the light irradiation site.
  • Analysis of skin samples obtained 72 hours post-PDT indicated an approximate 50% reduction of sebaceous glands with a 100 J/cm 2 red light dose applied 45 or 60 minutes after LFI-injection (Figure 6). Sebaceous gland counts for skin samples obtained from mice treated with PDT 7 days before were no different from control levels.
  • PDT treatment of a patient with a lower light dose 1 hour post- infusion of LFI A female patient is diagnosed with recurrent stage II HS, with multiple widely separated painful inflammatory nodules, with odious discharge, in the right axillae. In preparation for the treatment, axillae hairs around the lesions are carefully shaved. The patient is given a 10-minute intravenous infusion of Lemuteporfin at a dose of 14 mg/m 2 . One hour after the administration of the drug, the patient receives a direct exposure of the entire right axillae to red light (at a 690 nm wavelength) at a dose of 75 J/cm 2 using light- emitting diodes (LED). Such a treatment is repeated three times at a three week interval between the treatments.
  • LED light- emitting diodes
  • PDT treatment of a patient with a higher light dose 12 hours post- infusion of LFI A female patient is diagnosed with stage I HS, with two separated painful inflammatory nodules, with odious discharge, in the left inframammary area. The patient is given a 10-minute intravenous infusion of Lemuteporfin at a dose of 14 mg/m 2 . Twelve hours after the administration of the drug, the patient receives a direct exposure of the affected area (a circle of 4 cm diameter, containing both active nodules and the surrounding skin) to red light (at a 690 nm wavelength) at a dose of 180 J/cm 2 using light-emitting diodes (LED). Such a treatment is repeated three times at a weekly interval between the treatments.
  • LED light-emitting diodes

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Abstract

L'invention propose des procédés de traitement et/ou de prévention photodynamiques de l'hidradenitis suppurativa (HS) chez un sujet. Le procédé recourt à l'administration par la voie générale d'un photosensibilisant hydrophobe et/ou lipophile à un sujet qui souffre de HS puis à l'exposition du tissu affecté à de l'énergie d'une longueur d'onde capable d'activer le photosensibilisant.
PCT/CA2007/001971 2006-11-03 2007-11-02 Thérapie photodynamique pour le traitement de l'hidradenitis suppurativa WO2008052350A1 (fr)

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2374996C1 (ru) * 2008-08-28 2009-12-10 Константин Александрович Корейба Способ оперативного лечения подмышечного гидраденита с гнойно-свищевой инфильтрацией
CN102174478A (zh) * 2011-01-05 2011-09-07 复旦大学 一种光敏剂结合蛋白/多肽及其在光动力基因治疗中的应用
EP2424536A2 (fr) * 2009-04-28 2012-03-07 Ceramoptec Industries, Inc. Nouvelles formulations de photosensibilisateurs pour administration orale
WO2009093144A3 (fr) * 2008-01-25 2013-01-03 Qlt, Inc.Lau Thérapie photodynamique de troubles des glandes sébacées
US8929978B2 (en) 2011-01-27 2015-01-06 Nitto Denko Corporation Phototherapy devices and methods comprising optionally substituted terphenyl and quaterphenyl compounds
US9112159B2 (en) 2012-12-10 2015-08-18 Nitto Denko Corporation Bipolar hosts for light emitting devices
US9263681B2 (en) 2012-12-10 2016-02-16 Nitto Denko Corporation Organic light emitting host materials
CN105412924A (zh) * 2014-08-22 2016-03-23 苏州大学 具有血液稳定性及靶向性的含糖光动力学疗法纳米粒子及其制备方法
US9614162B2 (en) 2012-12-17 2017-04-04 Nitto Denko Corporation Light-emitting devices comprising emissive layer
US10668167B2 (en) 2016-06-02 2020-06-02 Abbvie Inc. Glucocorticoid receptor agonist and immunoconjugates thereof
US10772970B2 (en) 2017-12-01 2020-09-15 Abbvie Inc. Glucocorticoid receptor agonist and immunoconjugates thereof
EP3989960A4 (fr) * 2019-06-25 2023-06-28 Dusa Pharmaceuticals, Inc. Méthodes de réduction de la douleur au cours d'une thérapie photodynamique d'une kératose actinique

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
GOLD ET AL.: "ALA-PDT and blue light therapy for hidradenitis suppurativa", JOURNAL OF DRUGS IN DERMATOLOGY, vol. 3, 2004, pages S32 - S39 *
GOLD: "Aminolevulinic acid photodynamic therapy for hidradenitis suppurativa", DERMATOLOGICAL CLINICS, vol. 25, January 2007 (2007-01-01), pages 67 - 73 *
SINGER ET AL.: "Hidradenitis suppurativa", SEMINARS IN COLON AND RECTAL SURGERY, vol. 14, no. 4, 2003, pages 186 - 195 *
STRAUSS ET AL.: "Photodynamic therapy using aminolaeulinic acid does not lead to clinical improvement in hidradenitis suppurativa", BRITISH JOURNAL OF DERMATOLOGY, vol. 152, no. 4, 2005, pages 803 - 804 *
YU ET AL.: "Hidradenitis suppurativa: A disease of follicular epithelium rather than apocrine glands", BRITISH JOURNAL OF DERMATOLOGY, vol. 122, 1990, pages 763 - 769 *

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WO2009093144A3 (fr) * 2008-01-25 2013-01-03 Qlt, Inc.Lau Thérapie photodynamique de troubles des glandes sébacées
RU2374996C1 (ru) * 2008-08-28 2009-12-10 Константин Александрович Корейба Способ оперативного лечения подмышечного гидраденита с гнойно-свищевой инфильтрацией
EP2424536A2 (fr) * 2009-04-28 2012-03-07 Ceramoptec Industries, Inc. Nouvelles formulations de photosensibilisateurs pour administration orale
CN102695509A (zh) * 2009-04-28 2012-09-26 拜莱泰克研究有限公司 新的口服光敏剂制剂
JP2012525411A (ja) * 2009-04-28 2012-10-22 セラムオプテック インダストリーズ インコーポレーテッド 経口投与のための新規の光増感剤製剤
EP2424536A4 (fr) * 2009-04-28 2012-10-31 Ceramoptec Gmbh Nouvelles formulations de photosensibilisateurs pour administration orale
CN102174478A (zh) * 2011-01-05 2011-09-07 复旦大学 一种光敏剂结合蛋白/多肽及其在光动力基因治疗中的应用
CN102174478B (zh) * 2011-01-05 2014-08-06 复旦大学 一种光敏剂结合蛋白/多肽及其在光动力基因治疗中的应用
US8929978B2 (en) 2011-01-27 2015-01-06 Nitto Denko Corporation Phototherapy devices and methods comprising optionally substituted terphenyl and quaterphenyl compounds
EP2668247B1 (fr) * 2011-01-27 2016-12-28 Nitto Denko Corporation Dispositifs et méthodes de photothérapie comprenant des composés terphényle et quaterphényle facultativement substitués
US9112159B2 (en) 2012-12-10 2015-08-18 Nitto Denko Corporation Bipolar hosts for light emitting devices
US9263681B2 (en) 2012-12-10 2016-02-16 Nitto Denko Corporation Organic light emitting host materials
US9614162B2 (en) 2012-12-17 2017-04-04 Nitto Denko Corporation Light-emitting devices comprising emissive layer
CN105412924A (zh) * 2014-08-22 2016-03-23 苏州大学 具有血液稳定性及靶向性的含糖光动力学疗法纳米粒子及其制备方法
CN105412924B (zh) * 2014-08-22 2018-10-16 苏州大学 具有血液稳定性及靶向性的含糖光动力学疗法纳米粒子及其制备方法
US10668167B2 (en) 2016-06-02 2020-06-02 Abbvie Inc. Glucocorticoid receptor agonist and immunoconjugates thereof
US10772970B2 (en) 2017-12-01 2020-09-15 Abbvie Inc. Glucocorticoid receptor agonist and immunoconjugates thereof
EP3989960A4 (fr) * 2019-06-25 2023-06-28 Dusa Pharmaceuticals, Inc. Méthodes de réduction de la douleur au cours d'une thérapie photodynamique d'une kératose actinique

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