WO2022234064A1 - Topical capsaicinoids for treating a neuropathic condition in covid-19 patients - Google Patents
Topical capsaicinoids for treating a neuropathic condition in covid-19 patients Download PDFInfo
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- WO2022234064A1 WO2022234064A1 PCT/EP2022/062244 EP2022062244W WO2022234064A1 WO 2022234064 A1 WO2022234064 A1 WO 2022234064A1 EP 2022062244 W EP2022062244 W EP 2022062244W WO 2022234064 A1 WO2022234064 A1 WO 2022234064A1
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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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- topical admin istration has been effected so that the one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, are preferably removed from the skin.
- the neuropathic condition such as pain relief may last for up to 90 days or even longer.
- the neuropathic condition to be treated according to the invention may cause neuropathic symp toms such as numbness, tingling, pain or impaired sensory function in hands and/or feet, clumsiness in fingers, peripheral muscular weakness, or difficulties in walking. Further symptoms and signs according to the invention may be tingling; numbness; sharp, burning, shooting, or electric-like pain; paresthesia; allodynia; hyperalgesia and hyperpathia; motor dysfunction (for example foot or wrist drop, symmetric motor weakness, difficulty buttoning a shirt or holding a pen); and myalgias or muscle cramps.
- neuropathic symp toms such as numbness, tingling, pain or impaired sensory function in hands and/or feet, clumsiness in fingers, peripheral muscular weakness, or difficulties in walking.
- Further symptoms and signs according to the invention may be tingling; numbness; sharp, burning, shooting, or electric-like pain; paresthesia; allodynia; hyperalges
- the treatment of the neuropathic condition is for regenerating and/or restoring sen sory nerve fibers.
- the neuropathic condition to be treated preferably the neuropathic pain to be treated, is
- neuropathic pain preferably pre-existing chronic neu ropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mo noneuropathic pain
- the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-
- the 16 patients as compiled in the following table receive capsaicin by means of topical appli cation of one or more high-concentration capsaicin topical patches for treating neuropathic pain:
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Abstract
The invention relates to one or more high-concentration capsaicinoid topical dose units for use in the treatment of a neuropathic condition, preferably neuropathic pain, in a patient who is or who was previously infected with a coronavirus, wherein each of said one or more high-concentration capsaicinoid topical dose units contains capsaicinoid, preferably capsaicin, at a concentration of at least 5 wt.-%, relative to the total weight of the dose unit.
Description
Topical capsaicinoids for treating a neuropathic condition in COVID-19 patients
[0001] The invention relates to one or more high-concentration capsaicinoid topical dose units for use in the treatment of a neuropathic condition, preferably neuropathic pain, in a patient who is or who was previously infected with a coronavirus, preferably severe acute respiratory syndrome coronavirus 2, wherein each of said one or more high-concentration capsaicinoid topical dose units contains capsai cinoid, preferably capsaicin, at a concentration of at least 5 wt.-%, relative to the total weight of the dose unit.
[0002] A significant number of patients currently undergoing or previously having undergone corona virus disease 2019 (COVID-19) require pain treatment. The painful condition may already have preex isted prior to infection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and may have worsened in the course of COVID-19, or the painful condition may have developed in the course and/or as a consequence of COVID-19. Further, the painful condition may be acute or chronic, typically neuropathic, i.e. caused by damage or disease affecting the somatosensory nervous system.
[0003] Various painful conditions can be associated to COVID-19 disease. For example, F. Aksan et al., Journal of Neuro Virology, https://doi.org/10.1007/sl3365-020-00887-4 relates to a COVID-19 pa tient with intense burning pain. A.A. Joyce et al., Pain Medicine, 00(0), 2020, 1-12 relates to changes in interventional pain physician decision-making, practice patterns, and mental health during the early phase of the SARS-CoV-2 global pandemic. H.I. Kemp et al., British Journal of Anaesthesia, 125 (4): 436e449 (2020) relates to implications for rehabilitation with regard to chronic pain after COVID-19. L. Killion et al., BMJ Case Rep 2021;14:e240863. doi: 10.1136/bcr-2020-240863 relates to rare cutane ous manifestation of COVID-19. Ch.H. Meyer-FrieBem et al., www.painreportsonline.com, 6 (2021) e893, 1-7, http://dx.doi.org/10.1097/PR9.0000000000000893 is a narrative review of current knowledge of pain during and after COVID-19 in Germany and worldwide. A. Nalbandian et al., Nature Medicine, 27, pages601-615(2021), https://doi.org/10.1038/s41591-021-01283-z relates to post-acute COVID-19 syndrome. J. Blanch-Rubio et al., AGING 2020, Vol. 12, No. 20, relates to the influence of anti -osteo porosis treatments on the incidence of COVID-19 in patients with non-inflammatory rheumatic condi tions. W. Sun et al., Frontiers in Microbiology, 24 September 2020 | https://doi.org/10.3389/ ffnicb.2020.572318 relates to the management of immunity alteration-induced chronic pain during the coronavirus disease-2019 (COVID-19) pandemic. I.P.E. Widyadharma et al., The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2020) 56: 121 https://doi.org/10.1186/s41983-020-00258-0 is a literature review with regard to pain as clinical manifestations of COVID-19 infection and its manage ment in the pandemic era.
[0004] Among these painful conditions, neuropathies appear to be predominant and various scientific publications pertain to neuronal implications of COVID-19 and COVID-19 associated painful neurop athies. For example, L. Abdelnour et al., Journal of the Formosan Medical Association, Volume 119, Issue 6, June 2020, Pages 1119-1120 relates to COVID 19 infection presenting as motor peripheral neuropathy. A.N. Ozdag Acarli et al., Arch Neuropsychiatry 2020;57: 154-159 relates to the observation of neurological findings and symptoms during the combat against a pandemic with regard to coronavirus disease 2019 (COVID-19) from the point of view of neurologists. S. Andalib et al., Current Neurology and Neuroscience Reports (2021) 21: 9, https://doi.org/10.1007/sl l910-021-01102-5 relates to periph eral nervous system manifestations associated with COVID-19. N. Attal et al., www.painre- portsonline.com, 6 (2021) e884, 1-6, http://dx.doi.org/10.1097/PR9.0000000000000884 relates to the potential for increased prevalence of neuropathic pain after the COVID-19 pandemic. B.L. Bureau et al., (November 12, 2020), Cureus 12(1 l):el 1452. DOI 10.7759/cureus.l 1452 relates to peripheral neu ropathy as a complication of SARS-Cov-2. M. Cacciavillani et al., Muscle & Nerve, DOI: 10.1002/mus.27083, E7/8 relates to pure sensory neuralgic amyotrophy in COVID-19 infection. X. Cao et al., Journal of Pain Research 2020: 13 2361-2365 relates to a case report regarding herpes zoster and postherpetic neuralgia in an elderly patient with critical COVID-19. A.J. McFarland et al., www.painre- portsonline.com, 6 (2021) e885, 1-10, http://dx.doi.org/ 10.1097/ PR9.0000000000000885 relates to im plications for COVID-19 and pain with regard to neurobiology of SARS-CoV-2 interactions with the peripheral nervous system. D. Kersebaum et al., www.painreportsonline.com, 5 (2020) e858 1-10, http://dx.doi.org/10.1097/ PR9.0000000 000000858 relates to the early influence of COVID-19 pan demic associated restrictions on pain, mood, and everyday life of patients with painful polyneuropathy. C. Miller et al., Physical Therapy, 2021;101: 1-8 is a retrospective case series of 15 patients in critical care having brachial plexus neuropathies during the COVID-19 pandemic. P. Novak, eNeurologicalSci Volume 21, December 2020, 100276 is a case report with regard to post COVID-19 syndrome associated with orthostatic cerebral hypoperfusion syndrome, small fiber neuropathy and benefit of immunother apy.
[0005] The known treatment options for neuropathic conditions, preferably neuropathic pain, in pa tients who are currently infected or who were previously infected with a coronavirus, preferably severe acute respiratory syndrome coronavirus 2, are not satisfactory in every respect and there is a demand for improved treatment options.
[0006] It is an object of the invention to provide advantageous medicaments for the treatment of a neuropathic condition, preferably neuropathic pain, in patients who are currently infected or who were previously infected with a coronavirus, preferably with severe acute respiratory syndrome coronavirus 2. The medicaments should provide improved pain treatment at higher safety and/or improved
tolerability and/or improved compliance and/or for extended periods of time. Further, the medicaments should have neglectable or no interactions with other medicaments which are used for treating other aspects of COVID-19 disease.
[0007] This object has been achieved by the subject-matter of the patent claims.
[0008] The invention relates to one or more high-concentration capsaicinoid topical dose units for use in the treatment of pain in a patient who is or who was previously infected with a coronavirus, preferably with SARS CoV-2 vims, wherein each of said one or more high-concentration capsaicinoid topical dose units contains capsaicinoid, preferably capsaicin, at a concentration of at least 5 wt.-%, relative to the total weight of the dose unit.
[0009] The one or more high-concentration capsaicinoid topical dose units according to the invention contain capsaicinoid and are capable of releasing capsaicinoid to the skin when they are applied to the skin of the patient. Thus, the present invention involves topical administration of capsaicinoid by apply ing the one or more high-concentration capsaicinoid topical dose units to the skin of the patient. Typi cally, the one or more high-concentration capsaicinoid topical dose units remain on the patient's skin for a comparatively short period of time, typically not more than 1 hour, as this period of time is typically sufficient in order to topically administer a therapeutically effective dose of capsaicinoid to the skin of the patient.
[0010] The one or more high-concentration capsaicinoid topical dose units, preferably high-concentra tion capsaicinoid pharmaceutical patches for use according to the invention contain capsaicinoid, pref erably capsaicin {i.e. (E)-8-methyl-N-vanillyl-6-nonenamide, trans-8-methyl-N-vanillyl-6-nonena- mide, 6-nonenamide, (E)-N-[(4-hydroxy-3-methoxyphenyl) methyl]-8-methyl}.
[0011] Capsaicinoids are known to the skilled person and commercially available. Besides capsaicin, preferred capsaicinoids according to the invention include but are not limited to zucapsaicin (cis-capsa- icin, Civamide), (6,7-)dihydrocapsaicin, norcapsaicin, nordihydrocapsaicin I, nordihydrocapsaicin II, homocapsaicin I, homocapsaicin II, homodihydrocapsaicin I, homodihydrocapsaicin II, nomorcapsai- cin, nomordihydrocapsaicin, octanoyl vanillylamide, nonanoyl vanillylamide (Nonivamide), decanoyl vanillylamide, and mixtures thereof. Preferred capsaicionoids are selected from capsaicin, dihydrocap saicin, nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin, nonivamid, and capsazepin.
[0012] Capsaicin and capsaicinoids according to the invention are N-acyl derivatives of vanillylamine having different acyl chains R, as shown here below:
[0013] In a preferred embodiment, the one or more high-concentration capsaicinoid topical dose units, preferably high-concentration capsaicin pharmaceutical patches, for use according to the invention con tain capsaicin but essentially no other capsaicinoid.
[0014] For the purpose of the specification, a "dose unit" is defined as a predetermined quantity of a pharmaceutical formulation containing a high concentration of capsaicinoid for topical application to the skin of a patient.
[0015] For example, when the pharmaceutical formulation is a cream provided in a dispensing device (e.g. tube), a dose unit according to the invention may be e.g. a strand of cream of predetermined length taken from the dispensing device. Said strand of cream of predetermined length contains a predeter mined dose of capsaicinoid which, when the strand of cream is applied to and spread over the painful skin of the patient, is partially administered to the patient. A skilled person recognizes that creams, gels, ointments and other liquid or semisolid formulations may be applied to the skin at various thicknesses so that the applied dose per area of skin, e.g. expressed in terms of pg/cm2, may vary. However, as the dose unit is typically applied to the skin for a comparatively short application period of time before it is removed, e.g. 15 to 90 minutes, preferably 30 to 60 minutes, these potential variations in thickness will typically not significantly alter the administered dose of capsaicinoid. Typically, within such compara tively short application periods, less than 100% of the capsaicinoid that was originally contained in the
dose units will be administered, whereas a significant quantity of capsaicinoid will be removed along with the remainder of the dose unit at the end of the application period.
[0016] Likewise, when the pharmaceutical formulation is provided in form of a topical patch, a dose unit according to the invention may be a patch that is optionally cut to match the size and shape of the treatment area. Said patch contains a predetermined dose of capsaicinoid which, when the patch is ap plied to the painful skin of the patient, is partially administered to the patient.
[0017] Irrespective of the type of pharmaceutical formulation (e.g. cream, gel, ointment, or patch), the one or more topical dose units according to the invention contain a comparatively high concentration of capsaicinoid of at least 5 wt.-%, preferably at least 6.0 wt.-%, more preferably at least 7.0 wt.-%, most preferably at least or about 8.0 wt.-%, relative to the total weight of the dose units.
[0018] For the purpose of the specification, unless expressly stated otherwise, "high-concentration cap saicinoid topical dose unit" refers to a dose unit comprising capsaicinoid at a concentration of at least 5 wt.-%, preferably at least or about 8 wt.-%, relative to the total weight of dose unit.
[0019] Preferably, the high-concentration capsaicinoid topical dose unit according to the invention in each case is a high-concentration capsaicinoid pharmaceutical patch comprising capsaicinoid at a con centration of at least 5 wt.-%, preferably at least 6.0 wt.-%, more preferably at least 7.0 wt.-%, most preferably at least or about 8.0 wt.-%, relative to the total weight of the patch without release liner.
[0020] Preferably, the one or more high-concentration capsaicinoid pharmaceutical patches each com prise a backing layer, an adhesive layer, and a release liner; and wherein the content of capsaicinoid is at least 5.0 wt.-%, more preferably at least 6.0 wt.-%, still more preferably at least 7.0 wt.-%, most preferably at least or about 8.0 wt.-%, relative to the total weight of a pharmaceutical patch without release liner. Preferably, the capsaicinoid is contained in the adhesive layer (drug -in-adhesive).
[0021] For the purpose of the specification, a high-concentration capsaicinoid pharmaceutical patch comprising a backing layer, an adhesive layer, and a release liner; wherein the content of capsaicinoid is about 8.0 wt.-%, relative to the total weight of a pharmaceutical patch without release liner, is also referred to as "8% capsaicinoid patch" .
[0022] Preferably, the one or more high-concentration capsaicinoid pharmaceutical patches are cutane ous patches containing at least 400 micrograms of capsaicinoid per cm2 of patch, more preferably at least 500 micrograms of capsaicinoid per cm2 of patch, still more preferably at least 600 micrograms of
capsaicinoid per cm2 of patch, most preferably at least or about 640 micrograms of capsaicinoid per cm2 of patch.
[0023] Preferably, the one or more high-concentration capsaicinoid pharmaceutical patches are cutane ous patches each containing 640 micrograms of capsaicinoid per cm2 of patch and having an area of 280 cm2 (14 cm x 20 cm) such that each patch contains a total of 179 mg of capsaicinoid. Preferably, each high-concentration capsaicinoid pharmaceutical patch consists of an adhesive side containing the active substance and an outer surface backing layer. The adhesive side is preferably covered with a removable release liner. Preferably, the adhesive side is composed of a matrix comprising capsaicinoid, silicone adhesives, diethylene glycol monoethyl ether, silicone oil and ethylcellulose. Preferably, the surface backing layer is composed of a polyethylene terephthalate fdm with siliconized inner side. Preferably, the removable protective layer (release liner) is composed of a polyester fdm coated with a fluoropoly- mer. High-concentration capsaicinoid pharmaceutical patches of this type (8% capsaicinoid patches) are commercially available under the tradename Qutenza®.
[0024] Preferably, the one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, are not per manently applied to the skin of the patient but only for a comparatively short application period that is needed in order to topically administer capsaicinoid from the one or more dose units and patches, re spectively, into the patient's skin. Administration is preferably locally, i.e. intradermally, but not transcutaneously (e.g. systemically).
[0025] The one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, are preferably for sin gle use. Thus, a high-concentration capsaicinoid topical dose unit once applied typically is not and can not be reused as such. However, the treatment according to the invention is not limited to a one time treatment only, i.e. it is rather contemplated that additional high-concentration capsaicinoid topical dose units are subsequently used for continued treatment.
[0026] When the one or more high-concentration capsaicinoid topical dose units according to the in vention are provided in form of one or more high-concentration capsaicinoid pharmaceutical patches, said patches are preferably cut to match the size and shape of the treatment area. Preferably, the one or more high-concentration capsaicinoid pharmaceutical patches are cut prior to removal of the release liner. When treating feet, the one or more high-concentration capsaicinoid pharmaceutical patches are preferably wrapped around the dorsal, lateral and plantar surfaces of each foot to completely cover the treatment area.
[0027] Preferably, the one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, are applied to the skin of the patient for an application period of 15 to 90 minutes, preferably 30 to 60 minutes, and subsequently removed.
[0028] Preferably, the one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, are applied to the most painful skin areas (using up to a maximum of 4 high-concentration capsaicinoid dose units and high-concentration capsaicinoid pharmaceutical patches, respectively). For the purpose of the spec ification, applying " one or more high-concentration capsaicinoid topical dose units, preferably one or more high-concentration capsaicinoid pharmaceutical patches to the skin " refers to simultaneous or essentially simultaneous use of 1, 2, 3 or 4 high-concentration capsaicinoid dose units and high-concen- tration capsaicinoid pharmaceutical patches, respectively, preferably 1, 2, 3 or 4 8% capsaicinoid patches. More than a single high-concentration capsaicinoid pharmaceutical patch may be needed be cause the area of the skin of the patient to be covered with a high-concentration capsaicinoid pharma ceutical patch is larger than can be covered with a single high-concentration capsaicinoid pharmaceutical patch.
[0029] The painful area is preferably determined by the physician and marked on the skin. The one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, are preferably applied to intact, non-irri- tated, dry skin, and allowed to remain in place for an application period of 15 to 45 minutes, preferably 30 minutes for the feet (e.g. for treating HIV-associated neuropathy, painful diabetic peripheral neurop athy) and for an application period of 45 to 75 minutes, preferably 60 minutes for other locations (e.g. for treating postherpetic neuralgia). In case of high-concentration pharmaceutical patches, they are pref erably first cut to match the size and form of the painful area of the skin, and subsequently applied to the skin.
[0030] For the purpose of the specification, unless expressly stated otherwise, "application period " preferably refers to a period of 15 to 90 minutes, preferably 30 to 60 minutes, during which the one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches are applied to the skin of the patient be fore they are removed.
[0031] After removal of the one or more high-concentration capsaicinoid topical dose units, preferably one or more high-concentration capsaicinoid pharmaceutical patches from the skin, a cleansing gel is preferably applied liberally to the treatment area and left on for at least one minute. The cleansing gel is
then preferably wiped off with dry gauze to remove any remaining capsaicinoid from the skin. After the cleansing gel has been wiped off, the area of the skin is preferably gently washed with soap and water. A suitable cleansing gel may contain macrogol 300, carbomer, purified water, sodium hydroxide, diso dium edetate, and butyl hydroxy anisole.
[0032] After application periods of e.g. 15 to 90 minutes, preferably 30 to 60 minutes, topical admin istration has been effected so that the one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, are preferably removed from the skin. When proceeding this way, after removal from the skin, as a consequence of the administered dose of capsaicinoid, treatment of the neuropathic condition such as pain relief may last for up to 90 days or even longer.
[0033] Preferably, the one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, are applied to the skin of the patient, remain on the skin for an application period thereby topically administering capsaicinoid during the application period, and are subsequently removed, whereby as a consequence of topical administration of capsaicinoid by means of the one or more high-concentration capsaicinoid topical dose units, preferably one or more high-concentration capsaicinoid pharmaceutical patches, the patient preferably perceives relief of signs and symptoms of neuropathic pain for a period of at least 4 weeks, more preferably at least 6 weeks, still more preferably at least 8 weeks; preferably by a change versus baseline of at least 2 points or at least 30% decrease on a numeric rating scale (NRS) pain rating scale. As it may take between 1 to 3 weeks from the application period until onset of analgesia, the period of pain relief does not necessarily commence immediately after the application period.
[0034] Subsequent application of one or more further high concentration capsaicinoid dose units ac cording to the invention, preferably one or more high concentration capsaicinoid pharmaceutical patches, may be preferably repeated after 2 to 4 months, preferably after 3 months, e.g. every 90 days. When application is repeated, said one or more further high concentration capsaicinoid dose units, pref erably high concentration capsaicinoid pharmaceutical patches, are preferably applied to the same pain ful area of the skin of the patient where the one or more further high-concentration capsaicinoid topical dose units, preferably one or more high-concentration capsaicinoid pharmaceutical patches, were also previously applied, i.e. 2 to 4 months ago. It is contemplated and preferred that treatment with one or more further high-concentration capsaicinoid topical dose units is continued also after the acute phase of the COVID-19 infection has ended.
[0035] It is contemplated according to the invention that the treatment area of the painful skin of the patient may be pre-treated with a topical anesthetic (e.g. topical lidocaine (4%), or topical lidocaine
(2.5%)/prilocaine (2.5%)) or the patient may be administered an oral analgesic prior to application of the one or more high-concentration capsaicinoid topical dose units according to the invention, preferably one or more high-concentration capsaicinoid pharmaceutical patches, to reduce potential application related discomfort. The topical anesthetic is preferably applied to cover the entire treatment area and surrounding 1 to 2 cm. Topical anesthetics are preferably removed prior to applying the one or more high-concentration capsaicinoid topical dose units, preferably one or more high-concentration capsai cinoid pharmaceutical patches.
[0036] The patient to be treated according to the invention is or was previously infected with a corona- virus, preferably with SARS CoV-2 virus.
[0037] For the purpose of the description, a patient who "is infected" with a coronavirus currently has a detectable viral load above the threshold of suitable means for detecting coronavirus, preferably SARS CoV-2 virus. Suitable means for detecting coronavirus are known to the skilled person and include but are not limited to antibody tests, such as SARS-CoV-2 rapid antibody tests based upon chromatographic immune assays. Other tests are PCR test. Preferably, coronavirus and SARS CoV-2 virus in a patient who "is infected" are determined by means of PCR tests.
[0038] For the purpose of the description, a patient who " was infected" with a coronavirus previously had a detectable viral load above the threshold of suitable means for detecting coronavirus, preferably SARS CoV-2 virus, preferably determined by antibody tests (see above). It is contemplated that the patient was never tested during the acute phase and therefore never had a documented positive PCR test. Typically, such patient currently has no detectable viral load above the threshold of suitable means for detecting coronavirus, preferably SARS CoV-2 virus, preferably determined by PCR. Suitable means for determining whether a patient was previously infected with a coronavirus, preferably SARS CoV-2 virus, are known to the skilled person. Preferably, coronavirus and SARS CoV-2 virus in a patient who "was infected" are determined by means of antibody tests. The antibodies are preferably directed towards the nucleocapsid or one or more spike proteins of the coronavirus.
[0039] For the purpose of the description, a patient who "is infected" with a coronavirus does not need to show any signs or symptoms of the infection (e.g. COVID-19). Likewise, a patient who "was infected" with a coronavirus does not need to show signs or symptoms of the infection (e.g. COVID-19).
[0040] Thus, infection with coronavirus, preferably SARS-CoV-2 virus, means (i) that the patient cur rently carries a viral load, or (ii) that the patient previously carried a viral load, whereas depending upon the time lapsed from viral infection, said patient typically may have detectable antibodies against coro navirus, preferably SARS-CoV-2 virus, produced due to an immune response to the previous infection.
[0041] While the type of coronavirus according to the invention is principally not particularly limited, the coronavirus is preferably a so-called severe acute respiratory syndrome-related coronavirus, more preferably a severe acute respiratory syndrome coronavirus 2 (SARS CoV-2).
[0042] In preferred embodiments, the coronavirus is the severe acute respiratory syndrome coronavirus 2 or a mutant of the severe acute respiratory syndrome coronavirus 2 selected from the group consisting of Cluster 5, Lineage B.1.1.7, Lineage B.1.1.207, Lineage B.1.1.317, Lineage B.1.1.318, Lineage B.1.429, Lineage B.1.525, Lineage B.1.526, Lineage B.1.618, Lineage P.1, and Lineage P.3.
[0043] Preferably, the patient suffers or suffered from a corona virus disease (COVID), preferably COVID-19.
[0044] For the purpose of the description, a patient " suffers " (is suffering) from a corona virus disease (COVID), preferably COVID-19, when the patient currently has signs or symptoms of corona virus disease (COVID), preferably COVID-19, and currently typically has a detectable viral load.
[0045] For the purpose of the description, a patient "suffered" from a corona virus disease (COVID), preferably COVID-19, when the patient previously had signs or symptoms of corona virus disease (COVID), preferably COVID-19, but (i) currently - besides the pain to be treated - does not necessarily still show any of such signs or symptoms any longer, or (ii) currently only shows a limited number of such signs or symptoms, or (iii) currently shows such signs or symptoms to a significant lower degree than previously.
[0046] Characteristic signs and symptoms of corona virus disease (COVID) and COVID-19 are known to the skilled person and include but are not limited to severe acute respiratory syndrome, cough, fever, cold, disturbance of olfactory sense, disturbance of gustatory sense, pneumonia, sore throat, breathless ness (dyspnea), headache, limb pain, anorexia, weight loss, nausea, vomiting, diarrhea, stomach ache, conjunctivitis, skin rash, sentinel node swelling, apathy, and somnolence.
[0047] Preferably, the corona virus disease is a severe acute respiratory syndrome (SARS), preferably SARS-CoV-2. In preferred embodiments, the patient is under intensive care.
[0048] In a preferred embodiment, the patient suffers from chronic corona virus disease syndrome (CCS), which is also known as "long COVID ", "post-acute sequelae of SARS-CoV-2 infection", " post acute sequelae of COVID-19 (PASC)", or " long-haul COVID" .
[0049] In preferred embodiments, the patient suffers from
(i) acute COVID-19 (signs and symptoms of COVID-19 for up to 4 weeks);
(ii) ongoing symptomatic COVID-19 (signs and symptoms of COVID-19 from 4 to 12 weeks);
(iii) post-COVID-19 syndrome (signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagno sis); or
(iv) long COVID (signs and symptoms that continue or develop after acute COVID-19; includes both ongoing symptomatic COVID-19 and post-COVID-19 syndrome, i.e. (ii) and (iii) defined above).
[0050] For the purpose of the description, the above stages (i) to (iv) of COVID-19 are defined in accordance with the COVID-19 rapid guideline: managing the long-term effects of COVID-19, NICE guideline [NG188], published on 18 December 2020.
[0051] For the purpose of the description, " COVID-19 neuropathic pain " refers to neuropathic pain due to SARS-CoV-2 infection, neuropathic pain linked to SARS-CoV-2 infection, COVID- 19-associated neuropathy, and the like.
[0052] In preferred embodiments, the patient suffers, or suffered or has suffered from a neurological disorder or disease, preferably selected from Guillain-Barre syndrome, myelitis and stroke.
[0053] Preferably, the neurological disorder or disease is due to corona virus disease (COVID), prefer ably COVID-19.
[0054] In preferred embodiments, prior to infection with the coronavirus, the patient suffered or has suffered from
(i) pre-existing neurological injury; and/or
(ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neuropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mononeuropathic pain.
[0055] For the purpose of the description, a patient who "suffered" from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, prior to infection with the coronavirus was diagnosed accordingly before infection with the coronavirus occurred. A patient who " has suffered " from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condi tion, preferably neuropathic pain, prior to infection with the coronavirus was likewise diagnosed accord ingly before infection with the coronavirus occurred, but currently is still suffering from the (i) pre-
existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, i.e. the (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neu ropathic pain, existed already before viral infection and is still currently ongoing or is aggravated by the COVID-19 infection .
[0056] Preferably, the pre-existing neuropathic condition, preferably neuropathic pain, is selected from the group consisting of postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radicu lopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neuropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small-fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-surgical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0057] In other preferred embodiments, prior to infection with the coronavirus, the patient neither suf fered from (i) pre-existing neurological injury nor from (ii) pre-existing neuropathic condition, prefera bly neuropathic pain.
[0058] Preferably, the neuropathic condition to be treated is neuropathic pain, preferably peripheral neuropathic pain. Preferably, the pain to be treated is selected from the group consisting of COVID-19 neuropathic pain (COVID-19-associated neuropathy), postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuro pathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neuropathic pain asso ciated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small-fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-surgical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0059] Preferably, when the patient suffered or has suffered from pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neuropathic pain, more preferably pre-ex isting chronic polyneuropathic pain or pre-existing chronic mononeuropathic pain; the pain to be treated is of the same type as the pre-existing neuropathic condition, preferably neuropathic pain.
[0060] Preferably, when the patient suffered or has suffered from pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neuropathic pain, more preferably pre-ex isting chronic polyneuropathic pain or pre-existing chronic mononeuropathic pain; the pre-existing neu ropathic condition may still be there, or may be deteriorated, but there are additional symptoms due to COVID-19 itself or due to the treatment received during the acute phase of COVID-19.
[0061] The neuropathic condition to be treated according to the invention may cause neuropathic symp toms such as numbness, tingling, pain or impaired sensory function in hands and/or feet, clumsiness in fingers, peripheral muscular weakness, or difficulties in walking. Further symptoms and signs according to the invention may be tingling; numbness; sharp, burning, shooting, or electric-like pain; paresthesia; allodynia; hyperalgesia and hyperpathia; motor dysfunction (for example foot or wrist drop, symmetric motor weakness, difficulty buttoning a shirt or holding a pen); and myalgias or muscle cramps.
[0062] Preferably, the neuropathic condition is associated with pain and sensory loss; preferably hy persensitivity, loss of sensation, or functional deficits such as numbness, tingling, and discomfort in the fingertips and toes, ascending from distal to proximal as the condition progresses.
[0063] Preferably, the treatment of the neuropathic condition is for increasing pain relief to more than 30% versus baseline, preferably at least 60% versus baseline, preferably on the NRS pain rating scale.
[0064] Preferably, the treatment of the neuropathic condition is for regenerating and/or restoring sen sory nerve fibers.
[0065] Preferably, the treatment of the neuropathic condition is for alleviating pain.
[0066] Preferably, the treatment of the neuropathic condition is for improving and/or maintaining sen sory function.
[0067] Preferably, the treatment of the neuropathic condition is local.
[0068] In preferred embodiments, the neuropathic condition to be treated, preferably the neuropathic pain to be treated, is
(i) chronic; and/or
(ii) moderate to severe neuropathic pain; and/or
(iii) due to or linked to infection with the coronavirus (e.g. COVID-19 neuropathic pain).
[0069] According to particularly preferred embodiments of the invention, the patient
- suffers from acute COVID-19 (NICE guideline [NG188]);
- prior to infection with the coronavirus, suffered from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neu ropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mo- noneuropathic pain;
wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-sur gical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0070] According to particularly preferred embodiments of the invention, the patient
- suffers from acute COVID-19 (NICE guideline [NG188]);
- prior to infection with the coronavirus, has suffered from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neuropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mononeuropathic pain; wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-sur gical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0071] According to particularly preferred embodiments of the invention, the patient
- suffers from acute COVID-19 (NICE guideline [NG188]);
- prior to infection with the coronavirus, neither suffered from (i) pre-existing neurological injury nor from (ii) pre-existing neuropathic condition, preferably neuropathic pain; wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably COVID-19 neuropathic pain.
[0072] According to particularly preferred embodiments of the invention, the patient
- suffers from ongoing symptomatic COVID-19 (NICE guideline [NG188]);
- prior to infection with the coronavirus, suffered from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neu ropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mo- noneuropathic pain;
wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-sur gical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0073] According to particularly preferred embodiments of the invention, the patient
- suffers from ongoing symptomatic COVID-19 (NICE guideline [NG188]);
- prior to infection with the coronavirus, has suffered from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neuropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mononeuropathic pain; wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-sur gical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0074] According to particularly preferred embodiments of the invention, the patient
- suffers from ongoing symptomatic COVID-19 (NICE guideline [NG188]);
- prior to infection with the coronavirus, neither suffered from (i) pre-existing neurological injury nor from (ii) pre-existing neuropathic condition, preferably neuropathic pain; wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably COVID-19 neuropathic pain.
[0075] According to particularly preferred embodiments of the invention, the patient
- suffers from post-COVID-19 syndrome (NICE guideline [NG188]);
- prior to infection with the coronavirus, suffered from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neu ropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mo noneuropathic pain;
wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-sur gical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0076] According to particularly preferred embodiments of the invention, the patient
- suffers from post-COVID-19 syndrome (NICE guideline [NG188]);
- prior to infection with the coronavirus, has suffered from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neuropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mononeuropathic pain; wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-sur gical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0077] According to particularly preferred embodiments of the invention, the patient
- suffers from post-COVID-19 syndrome (NICE guideline [NG188]);
- prior to infection with the coronavirus, neither suffered from (i) pre-existing neurological injury nor from (ii) pre-existing neuropathic condition, preferably neuropathic pain; wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably COVID-19 neuropathic pain.
[0078] According to particularly preferred embodiments of the invention, the patient
- suffers from long COVID (NICE guideline [NG188]);
- prior to infection with the coronavirus, suffered from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neu ropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mo noneuropathic pain;
wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-sur gical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0079] According to particularly preferred embodiments of the invention, the patient
- suffers from long COVID (NICE guideline [NG188]);
- prior to infection with the coronavirus, has suffered from (i) pre-existing neurological injury and/or (ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neuropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre-existing chronic mononeuropathic pain; wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably selected from the group consisting of COVID-19 neuropathic pain, postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radiculopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to myelitis, neuropathic pain due to cancer, trigeminal neuralgia, neu ropathic pain associated with Guillain-Barre syndrome, chemotherapy induced neuropathic pain, small- fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-sur gical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
[0080] According to particularly preferred embodiments of the invention, the patient
- suffers from long COVID (NICE guideline [NG188]);
- prior to infection with the coronavirus, neither suffered from (i) pre-existing neurological injury nor from (ii) pre-existing neuropathic condition, preferably neuropathic pain; wherein the pain to be treated is neuropathic pain, preferably peripheral neuropathic pain; more prefer ably COVID-19 neuropathic pain.
[0081] The patients to be treated in accordance with the invention are not particularly limited. In pre ferred embodiments, the patients are female. In other preferred embodiments, the patients are male. In preferred embodiments, the patients are adults. In preferred embodiments, the patients are elderly, pref erably are at least 60 years, more preferably at least 65 years.
[0082] In preferred embodiments, especially when the acute phase of COVID-19 is still ongoing, the patient receives additional medicaments for treating viral infection, signs and/or symptoms thereof. Such
additional medicaments are not particularly limited and may contain as pharmacologically active ingre dients e.g. dexamethasone, remdesivir, chloroquine, lopinavir, or ritonavir.
[0083] The following example further illustrates the invention but is not to be construed as limiting its scope.
Example 1:
[0084] The 16 patients as compiled in the following table receive capsaicin by means of topical appli cation of one or more high-concentration capsaicin topical patches for treating neuropathic pain:
7 = female; M = male; A = acute COVID- 19; O = ongoing symptomatic COVID- 19; P = post-COVID- 19 syndrome; L = long COVID.
[0085] pre-existing neuropathic pain / pain treated:
1 postherpetic neuralgia PHN
2 chronic painful radiculopathy
3 cervical radiculopathy
4 diabetic painful neuropath DPN
5 spinal cord injury pain
6 neuropathic pain due to myelitis
7 neuropathic pain due to cancer
8 trigeminal neuralgia
9 neuropathic pain associated with Guillain-Barre syndrome
10 chemotherapy induced neuropathic pain, small -fiber neuropathy, chronic idiopathic axonal polyneu ropathy, post-traumatic neuropathic pain, post-surgical neuropathic pain
11 HIV infection-induced neuropathic pain
12 poststroke neuropathic pain
Claims
1. One or more high-concentration capsaicinoid topical dose units for use in the treatment of a neu ropathic condition, preferably neuropathic pain, in a patient who is or who was previously infected with a coronavirus, wherein each of said one or more high-concentration capsaicinoid topical dose units contains capsaicinoid at a concentration of at least 5 wt.-%, relative to the total weight of the dose unit.
2. The one or more high-concentration capsaicinoid topical dose units for use according to claim 1, wherein the coronavirus is a severe acute respiratory syndrome-related coronavirus, preferably a severe acute respiratory syndrome coronavirus 2.
3. The one or more high-concentration capsaicinoid topical dose units for use according to claim 1 or 2, wherein the coronavirus is a mutant of the severe acute respiratory syndrome coronavirus 2 selected from the group consisting of Cluster 5, Lineage B.l.1.7, Lineage B.1.1.207, Lineage B.1.1.317, Lineage B.1.1.318, Lineage B.1.429, Lineage B.1.525, Lineage B.1.526, Lineage B.1.618, Lineage P.1, and Lineage P.3.
4. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the patient suffers or suffered from a corona virus disease (COVID), preferably COVID-19; preferably wherein the corona virus disease is severe acute res piratory syndrome (SARS), preferably SARS-CoV-2.
5. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the patient suffers from chronic corona virus disease syndrome (CCS).
6. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the patient suffers from
(i) acute COVID-19,
(ii) ongoing symptomatic COVID-19,
(iii) post-COVID-19 syndrome, or
(iv) long COVID.
7. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the patient suffers or suffered from a neurological disorder or
disease; preferably selected from Guillain-Barre syndrome, myelitis and stroke; preferably wherein the neurological disorder or disease is due to corona virus disease (COVID), preferably COVID-19.
8. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the patient prior to infection with the coronavirus suffered or has suffered from
(i) pre-existing neurological injury; and/or
(ii) pre-existing neuropathic condition, preferably neuropathic pain, preferably pre-existing chronic neuropathic pain, more preferably pre-existing chronic polyneuropathic pain or pre existing chronic mononeuropathic pain.
9. The one or more high-concentration capsaicinoid topical dose units for use according to claim 8, wherein the pre-existing neuropathic condition, preferably neuropathic pain, is selected from the group consisting of postherpetic neuralgia (PHN), chronic painful radiculopathy, cervical radicu lopathy, diabetic painful neuropath (DPN), spinal cord injury pain, neuropathic pain due to mye litis, neuropathic pain due to cancer, trigeminal neuralgia, neuropathic pain associated with Guil lain-Barre syndrome, chemotherapy induced neuropathic pain, small-fiber neuropathy, chronic idiopathic axonal polyneuropathy, post-traumatic neuropathic pain, post-surgical neuropathic pain, HIV infection-induced neuropathic pain, and poststroke pain.
10. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the neuropathic condition is
(i) neuropathic pain, preferably peripheral neuropathic pain; and/or
(ii) sensory loss; preferably hypersensitivity, loss of sensation, or functional deficits such as numbness, tingling, and discomfort in the fingertips and toes, ascending from distal to prox imal as the condition progresses
11. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the neuropathic condition, preferably neuropathic pain, is
(i) chronic; and/or
(ii) moderate to severe neuropathic pain; and/or
(iii) due to or linked to infection with the coronavirus.
12 The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the treatment of the neuropathic condition is
(i) for regenerating and/or restoring sensory nerve fibers;
(ii) for alleviating pain;
(iii) for improving and/or maintaining sensory function; and/or
(iv) local.
13. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the one or more high-concentration capsaicinoid topical dose units are applied to the skin of the patient
(i) for an application period of 15 to 90 minutes, preferably 30 to 60 minutes, and subsequently removed; and/or
(ii) 2 to 4 months, preferably 3 months, e.g. 90 days, after previous topical administration of capsaicinoid.
14. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein the capsaicinoid is selected from the group consisting of capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin, nonivamid, and capsazepin; preferably capsaicin.
15. The one or more high-concentration capsaicinoid topical dose units for use according to any of the preceding claims, wherein each of said one or more high-concentration capsaicinoid topical dose units is a high-concentration capsaicinoid pharmaceutical patch comprising capsaicinoid at a concentration of 6.0 wt.-%, preferably at least 7.0 wt.-%, more preferably at least or about 8.0 wt.-%, relative to the total weight of the dose units; preferably wherein each high-concentration capsaicinoid pharmaceutical patch (i) comprises a backing layer, an adhesive layer, and a release liner; and wherein the content of capsaicinoid is at least 6.0 wt.-%, preferably about 8.0 wt.-%, relative to the total weight of the pharmaceutical patch without release liner; and/or (ii) comprises capsaicinoid at a content of at least 400 micrograms of capsaicinoid per cm2 of patch, preferably about 640 micrograms of capsaicinoid per cm2 of patch.
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| WO2024189202A1 (en) * | 2023-03-15 | 2024-09-19 | Lts Lohmann Therapie-Systeme Ag | Medical patch comprising capsaicin |
| WO2024189213A1 (en) * | 2023-03-15 | 2024-09-19 | Lts Lohmann Therapie-Systeme Ag | Medical patch comprising skin irritating active agent |
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| US20060222690A1 (en) * | 2005-03-30 | 2006-10-05 | Bley Keith R | Low-concentration capsaicin patch and methods for treating neuropathic pain |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024189202A1 (en) * | 2023-03-15 | 2024-09-19 | Lts Lohmann Therapie-Systeme Ag | Medical patch comprising capsaicin |
| WO2024189213A1 (en) * | 2023-03-15 | 2024-09-19 | Lts Lohmann Therapie-Systeme Ag | Medical patch comprising skin irritating active agent |
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