WO1994005293A1 - Compositions destinees au traitement de la peau, contenant du dimethylsulfone et de l'allopurinol ou l'oxypurinol - Google Patents

Compositions destinees au traitement de la peau, contenant du dimethylsulfone et de l'allopurinol ou l'oxypurinol Download PDF

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Publication number
WO1994005293A1
WO1994005293A1 PCT/GB1993/001877 GB9301877W WO9405293A1 WO 1994005293 A1 WO1994005293 A1 WO 1994005293A1 GB 9301877 W GB9301877 W GB 9301877W WO 9405293 A1 WO9405293 A1 WO 9405293A1
Authority
WO
WIPO (PCT)
Prior art keywords
oxypurinol
allopurinol
skin
methylsulphonylmethane
msm
Prior art date
Application number
PCT/GB1993/001877
Other languages
English (en)
Inventor
Aws Shakir Mustafa Salim
Original Assignee
Aws Shakir Mustafa Salim
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB929218774A external-priority patent/GB9218774D0/en
Application filed by Aws Shakir Mustafa Salim filed Critical Aws Shakir Mustafa Salim
Priority to AU49748/93A priority Critical patent/AU4974893A/en
Publication of WO1994005293A1 publication Critical patent/WO1994005293A1/fr

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Classifications

    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine

Definitions

  • the present invention pertains to pharmaceutically synergistic compositions suitable for use in improving the condition of the skin, which compositions comprise allopurinol or oxypurinol together with methylsulphonylmethane.
  • the present invention now provides a synergistic composition comprising allopurinol and/or oxypurinol with methylsulphonylmethane.
  • composition of the invention has been found surprisingly and unexpectedly to improve the condition of the skin by protecting it against many disorders .
  • disorders such as non-mechanical injury and degenerative disorders; affords a very effective therapy for a wide range of diseases be they inflammatory, endocrinal, metabolic or traumatic; besides enhancing the regenerative power of the skin as for example in wound healing. Consequently, the compositions of this invention are equipped with the novelty of combating the disease process while enhancing the repair of any damage that has been inflicted and increasing the resistance against recurrence of the disease.
  • compositions of the present invention exhibit the following actions: 1. Scavenging oxygen-derived free radicals which are cytotoxic agents implicated in tissue damage and injury besides impairing the process of healing and repair.
  • Cytoprotection which refers to sustaining the physio-chemical properties of biological tissues, thus increasing their resistance to noxious stimuli.
  • the improvement in the skin condition can also include maintenance of its vitality, smoothness, firmness and texture.
  • vasodilator substance such as menthol
  • menthol in order to further increase the effectiveness of the composition in the skin.
  • enhanced therapeutic gains have been noted with the incorporation of vitamins A and E in the compositions of the invention.
  • the present invention provides a pharmaceutical composition being presented in intimate admixture with a physiologically acceptable carrier for use in improving the condition of the skin.
  • this invention introduces a topical formulation consisting of the above composition in intimate admixture with a pharmaceutically acceptable vehicle.
  • a pharmaceutically acceptable vehicle should not be deleterious to biological tissues or incompatible with any of the ingredients of the formulation. Since some individuals have more sensitive skin than others, alternative vehicles to those used normally may have to be tried.
  • Suitable vehicles are well known in the art and are presented in all its standard publications such as the British National Formulary and British Pharmacopoeia. They include ointments and creams bases, lotions, pastes, jellies, sprays, aerosols and bath oils. Ointments and creams may contain oleaginous absorption colloidal clays, thickening agents such as gum tragacanth or sodium alginate and other pharmaceutically acceptable accessory ingredients such as humectants, preservatives, buffers and antioxidants which have utility in such formulations. In general, cream formulations are preferred as being most acceptable to the majority of users.
  • a particularly convenient base is one utilizing cetomacrogol, comprising for example 30% w/v cetomacrogol emulsifying ointment (30% w/v cetomacrogol emulsifying wax, 20% w/v liquid paraffin wax, 50% w/v white soft paraffin) in freshly boiled and cooled purified water__with for ' example 0.1% w/v chlorocresol or 0.08% w/v propyl hydroxybenzoate, 0.15% w/v methyl hydroxybenzoate and 1.5% w/v benzyl alcohol.
  • the topical formulations of the invention contain at least 0.5% w/w of each of its ingredients, preferably from 1 to 30% w/w and most preferably from 1 to 10% w/w, e.g. 5% methyl sulphonylmethane and 1% allopurinol or oxypurinol. Where menthol is included, this is generally used in an amount of from 1 to 30% w/w and most preferably from 1 to 5% w/w.
  • compositions of this invention can be administered in a suitable vehicle orally or parenterally, in particular by intravenous injection.
  • the active ingredients of the invention and any accompanying material may be presented as a draught in water or in a syrup, in capsules, sachets, boluses or tablets, as an aqueous or oleaginous solution or suspension or in suspension in a syrup, such suspensions optionally including suspending agents or as an oil-in-water or water-in-oil emulsion.
  • the compositions of the invention can be taken orally in an alcoholic drink be that a spirit, wine or beer.
  • the non-alcoholic forms of these drinks may also serve as vehicles for the oral consumption of the invention.
  • the invention can be added to fruit juices, mineral waters be they carbonated or not, and to all forms of soft drinks.
  • flavouring sweetening, preserving, thickening or emulsifying agents
  • Tablets may contain the ingredients of the invention and any accompanying material as a powder or granules optionally mixed with binders, lubricants, inert diluents or surface - active or dispersing agents.
  • ingredients of the invention and any accompanying material may be presented in sterile solutions or suspensions in aqueous or oleaginous vehicles, which may also contain preservatives and material for rendering the solution or suspension isotonic with the blood of the recipient.
  • aqueous or oleaginous vehicles which may also contain preservatives and material for rendering the solution or suspension isotonic with the blood of the recipient.
  • Such formulations may conveniently be presented in unit-dose or multi-dose sealed containers.
  • the ingredients of the invention are preferably presented in solution or suspension or emulsion at a concentration of from 0.5 to 15% w/v, more preferably from 1 to 5% w/v, advantageously in unit multi-dose form.
  • each of these doses contains 500mg methyl sulphonylmethane and 50mg allopurinol or oxypurinol.
  • the dosage may be given one or more times a day, preferably at intervals of from 2 to 8 hours, most preferably every 6 hours.
  • the ingredients of the invention are administered in a slow release or a sustained release vehicle, various suitable vehicles of this type being known in the art.
  • compositions of the invention can be directly delivered to the lung via smoke and in this respect, they can be added as a powder or solution to tobacco leaves or to the tobacco of cigarettes, cigars and pipes.
  • the invention may also be included as a solution or powder in cigarette filters or small delivery compartments incorporated in the cigarette. These compartments may also contain .the compositions of the invention in granules which evaporate upon contact with the smoke thereby delivering their substances to be carried by the smoke.
  • the formulation is applied onto the skin and/or mucosa from 1 to 3 times a day then spread over the area to be treated and gently rubbed in for a few minutes. It is advisable to leave the evening application overnight if repair of any skin damage is to be effected. It is not necessary to wash away the previous application in order to apply a fresh one, this however may simply be carried out using warm water alone or with soap.
  • vitamin A retinol
  • E alpha tocopheryl acetate
  • the formulae were prepared at a temperature of 25°C. Five grams of methyl sulphonylmethane are mixed with one gram of allopurinol or oxypurinol in a glass or stainless steel container then 94 grams of cetomacrogol 'A' (or 93 grams if menthol is to be used) are added and mixed for 10 minutes. After standing for 30 minutes, one gram of finely ground menthol crystals alone or with the above mentioned amounts of vitamins A and/or E can be added and mixed for 10 minutes. The product is then placed in a dark-coloured airtight glass container and stored at an optimal temperature of 26°c, and most preferably no higher, away from direct sunlight. After preparation, none of these formulations should be used for at least 24 hours, should not be left exposed to the air for long periods of time and should not be directly exposed to the sun.
  • the creams described in Example 1 can be applied several times a day.
  • the evening application may be left overnight and washed away the following morning using warm water with or without soap. Treatment may be for a few days or months depending on each case.
  • the daily application is limited to the period of exposure and is preferably twice a day, where one of the applications is used prior to the exposure to afford protection, and the other is used before retiring to bed and left overnight to induce therapy for any ultraviolet-induced damage to the skin.
  • the formulation may be applied once daily onto the parts of the skin to be protected such as the face and limbs prior to the exposure.
  • Application for therapeutic purposes is determined by the nature of the disease or disorder to be treated, e.g. dermatitis 5-10 days (unless caused by varicose veins when treatment is extended to 4 weeks), wound healing 2-3 weeks, varicose ulceration 12-16 weeks.
  • the application is 2 to 3 times daily, most preferably at 8 hourly intervals. Maintenance therapy after successful treatment or to sustain the condition of skin may require a once daily application to a particular part of the skin for months, years or even indefinitely.
  • Alcohol is a noxious substance which can produce direct and lasting damage to living tissues.
  • Application of this agent in high concentrations to the gastric mucosa disrupts its barrier causing hydrogen ion back diffusion and coagulative necrosis.
  • the alcohol-induced acute gastric mucosal injury is mediated by oxygen-derived free radicals.
  • This injury offers a good experimental model for use in the study of the mechanisms of tissue injury in living bodies and the various means which can be utilized in the protection against such injuries.
  • Dose dependant protection against the alcohol-induced acute gastric mucosal injury was afforded by each of allopurinol, oxypurinol and MSM.
  • the administration of combinations of allopurinol or oxypurinol with MSM enhanced the protection in a synergistic manner. This protection was not associated with any influences on gastric acid secretion, thus, reflecting cytoprotection.
  • each of allopurinol, oxypurinol and MSM affords cytoprotective activities against tissue injury but combinations of MSM and oxypurinol or allopurinol provide synergistically enhanced levels of activity.
  • the mechanism of this action is believed to be scavenging the oxygen derived free radicals which mediate tissue injury.
  • Alcohol-induced acute gastric mucosal injury has been utilized to study the influence of allopurinol, oxypurinol and MSM on the healing rate of biological tissues in vivo.
  • Administration of these agents stimulated the healing of the alcohol-induced injury and interacted to provide synergism without affecting the state of gastric acid secretion. Consequently, it appears that the advantageous action of stimulating the healing of tissue injury was achieved by mechanisms operating at cellular levels such as promotion of biosynthesis by sulphur and methyl group donation besides scavenging the oxygen-derived free radicals which impair healing by a direct deleterious effect upon tissues.
  • Example l.A The sunscreening effect of the formulation listed under Example l.A and its ability to protect patients against skin burns, erythema, itching and scaling, which occur following a few hours' exposure to the sun, was examined.
  • Complete protection (100%) was afforded by active therapy against all the adverse effects produced by exposure to the sunlight. This protection also extended to the prevention of skin burns or irritation. Controls had no such protection at all.
  • Example l.A The therapeutic efficacy of the formulation listed under Example l.A for the treatment of contact dermatitis was examined. Treatment was applied twice every day for 5 days. There were 16 controls (8 men and 8 women, age range 18 to 40 years, mean 26) and 14 treatment cases (8 men and 6 women, age range 19 to 46 years, mean 28) . While complete healing of the dermatitis was noted at the end of the study in all the active treatment cases (100%), only 2 controls (13%) demonstrated this favourable response.
  • Hyperkeratosis is a proliferative skin disorder which represents hyperplasia of the epidermis and may have a malignant potential.
  • the condition affects the exposed parts of the skin of middle aged people, particularly the face and upper limbs.
  • Treatment of these lesions by the twice daily application of the formulation listed under Example l.E for four weeks (18 cases, 10 women and 8 men with.an age range of 53 to 69 years, mean 61) caused complete shedding of the lesions and their replacement by normal skin in all cases. No response was noted in any of the control cases (21 patients, 12 women and 9 men with an age range of 55 to 71 years, mean 64) . It is, thus, construed that the formulation used stimulates repair of skin lesions.
  • Example l.C The therapeutic efficacy of the formulation listed under Example l.C in controlling the symptoms caused by skin burns resulting from exposure to the sun and in treating this condition was examined by its application onto the affected parts of skin every 8 hours for 10 days.
  • Within 24 hours of treatment all the symptoms of the burns (hyperaesthesia, itching, pain) were completely controlled in all of the members of the active therapy group but in none of the controls.
  • the burnt skin had been shed off and a return to normal skin was achieved by the 10th day of treatment in all cases.
  • Example l.F The efficacy of the formulation listed under Example l.F in maintaining the skin smoothness and avoiding its roughening and/or fissuring was examined in a group of women who were already using some form of beauty cream to this end and who had no previous history of any skin diseases. All the cases entered into the study abstained from using their original cream and were then randomized to the control or active therapy group and instructed to use their respective cream whether for the hands and/or face once daily before retiring to bed and to leave it overnight. Treatment was applied for 2 months. There were 32 cases in the active therapy group (age range 18 to 34 years, mean 26) and 34 cases in the control group (age range 18 to 36 years, mean 27) .
  • Example l.B Following excision and partial thickness skin grafting for deep burns extending over a surface area of 9 to 12% of the lower limbs, a liberal amount of the formulation listed under Example l.B or the control cream was applied over the grafted area before dressing it. Fifteen patients were randomized to the active therapy group (9 women and 6 men, age range 19 to 45 years, mean 31) and 16 patients were randomized to the control group (8 women and 8 men, age range 18 to 51 years, mean 34) . When the dressing was removed five days after grafting, ⁇ completely successful take was observed in all members of the active therapy group. Two controls (13%) , however, showed failure of graft taking. This study reflects the ability of the active treatment employed to enhance skin grafting.
  • the ulcer was dressed by open-weave Terylene (TM) and cotton gauze.
  • TM Terylene
  • the skin surrounding the ulcer was treated with propylene glycol monostearate then a below knee graduated compression bandage as described above was applied over the dressing. This procedure was repeated every day for 7 days then weekly until the ulceration had healed or until the end point of the study at 3 months. Patients were advised to sleep with the foot of the bed raised, to avoid long periods of standing without exercising the calf pump, to walk whenever possible and to elevate the leg when sitting.
  • Pruritis ani caused by anal warts may produce itching which is very difficult to treat until the warts have been removed.
  • a study was carried out on patients with this pruritis who were on the waiting list for some form of treatment for the warts to examine the therapeutic efficacy of the formulation listed under Example l.F in controlling symptoms. Twelve patients (7 women and 5 men, age range 18 to 28 years, mean 21) were randomized to the active therapy group and 10 patients (6 women and 4 men, age range 18 to 31 years, mean 25) were randomized to the control.-group. Patients were instructed to maintain a high degree of self hygiene, to wash the perinium with soap and water after every motion, and to apply the cream onto the perianal region 3 times every day for 5 days. Complete symptomatic control was achieved within 24 hours by all members of the active therapy group, but in none of the control patients.
  • Allopurinol or oxypurinol powder was dissolved in a few drops of 0.1M aqueous NaOH and then added to a solution of methyl sulphonylmethane (MSM) in double distilled water to prepare the following formulations:
  • Oxypurinol lOOmg + MSM 500mg Similarly, in other groups of ten healthy volunteers of ages ranging between 20 and 41 years, 5 grams of each of the formulations presented under Example 1 were applied onto the face, neck and shoulders once in the morning, once again in the morning and once in the evening, or once every 8 hours. Treatment was carried out for ten days. Each application was spread over the face, neck and shoulders, gently rubbed in for a few minutes then left for at least 3 hours before being washed away with warm water.
  • methylsulponylmethane and oxypurinol and/or allopurinol are advantageously used in amounts in the ratio 5:1, by weight, in the synergistic compositions of the invention, other ratios may also be used. Generally there is used a ratio of from 20:1 to 1:1, preferably from 10:1 to 3:1 most preferably about 5:1, by weight.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à des compositions synergiques comprenant du méthylsulfonylméthane et de l'oxypurinol et/ou de l'allopurinol, ainsi qu'à leur utilisation dans des formulations et méthodes thérapeutiques et prophylactiques destinées aux lésions et/ou maladies, et/ou états affectant la peau.
PCT/GB1993/001877 1992-09-04 1993-09-03 Compositions destinees au traitement de la peau, contenant du dimethylsulfone et de l'allopurinol ou l'oxypurinol WO1994005293A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU49748/93A AU4974893A (en) 1992-09-04 1993-09-03 Skin treatment compositions containing dimethylsulphone and allopurinol or oxypurinol

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB929218774A GB9218774D0 (en) 1992-09-04 1992-09-04 Synergistic composition for treating the skin
GB9218774.9 1992-09-04
GB9300650.0 1993-01-14
GB939300650A GB9300650D0 (en) 1992-09-04 1993-01-14 Synergistic compositions for treating the skin

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WO1994005293A1 true WO1994005293A1 (fr) 1994-03-17

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004105741A1 (fr) * 2003-05-30 2004-12-09 Gianfranco De Paoli Ambrosi Compositions cosmetiques et/ou pharmaceutiques a base de sulphone de dimethyle destinees au traitement et a la prevention d'irritations, d'inflammations et d'erythemes cutanes
JP2008291032A (ja) * 2008-06-04 2008-12-04 Paoli Ambrosi Gianfranco De ケミカルピーリングのための処方
FR2928543A1 (fr) * 2008-03-17 2009-09-18 Oreal Utilisation d'inhibiteurs de la xanthine oxydase pour la pigmentation capillaire
EP2114384A2 (fr) * 2007-02-15 2009-11-11 Derma-Young Ltd. Compositions et méthodes permettant d'améliorer l'administration transmuqueuse
EP2246057A1 (fr) 2009-04-29 2010-11-03 Nobera Pharma, S.L. Utilisation d'allopurinol pour le traitement d'une cutiréaction sur les mains et sur les pieds
US7973046B2 (en) 2006-06-01 2011-07-05 Nobera Pharma, S.L. Use of allopurinol for the treatment of palmar plantar erythrodysesthesia
WO2014024193A1 (fr) * 2012-08-07 2014-02-13 Prodel Pharma Ltd. Compositions et procédés d'administration rapide, à travers les muqueuses, d'ingrédients pharmaceutiques
WO2019077521A1 (fr) * 2017-10-17 2019-04-25 Alfakjn S.R.L. Composition liquide destinée à être utilisée comme anti-inflammatoire
WO2020033666A1 (fr) * 2018-08-09 2020-02-13 Asymmetric Therapeutics, Llc Compositions et procédés de traitement des effets secondaires associés à l'administration d'agents thérapeutiques

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2057263A (en) * 1979-08-30 1981-04-01 Herschler R J Compositions containing methylsulphonylmethane
EP0103836A2 (fr) * 1982-09-14 1984-03-28 Robert J. Herschler Compositions diététiques et pharmaceutiques à base de méthylsulfonylméthane

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2057263A (en) * 1979-08-30 1981-04-01 Herschler R J Compositions containing methylsulphonylmethane
EP0103836A2 (fr) * 1982-09-14 1984-03-28 Robert J. Herschler Compositions diététiques et pharmaceutiques à base de méthylsulfonylméthane

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SALIM A.S.: "Role of Oxygen derived free radicals in the mechanism of chronic gastric ulceration in the rat: Implications for Cytoprotection", DIGESTION, vol. 43, no. 1-2, 1989, pages 113 - 119 *

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2003238687B8 (en) * 2003-05-30 2009-08-06 Gianfranco De Paoli Ambrosi Cosmetic and/or pharmaceutical compositions comprising dimthylsulphone for the cure and prevention of irritation, inflammation and cutaneous erythema
JP2006525951A (ja) * 2003-05-30 2006-11-16 デ・パオリ・アムブロスィ、ジアンフランコ 刺激、炎症および皮膚紅斑の治療および予防のための化粧品および／または薬学的組成物
WO2004105741A1 (fr) * 2003-05-30 2004-12-09 Gianfranco De Paoli Ambrosi Compositions cosmetiques et/ou pharmaceutiques a base de sulphone de dimethyle destinees au traitement et a la prevention d'irritations, d'inflammations et d'erythemes cutanes
AU2003238687B2 (en) * 2003-05-30 2009-07-02 Gianfranco De Paoli Ambrosi Cosmetic and/or pharmaceutical compositions comprising dimthylsulphone for the cure and prevention of irritation, inflammation and cutaneous erythema
US8557829B2 (en) 2006-06-01 2013-10-15 Nobera Pharma, S.L. Use of allopurinol for the treatment of palmar plantar erythrodysesthesia
US7973046B2 (en) 2006-06-01 2011-07-05 Nobera Pharma, S.L. Use of allopurinol for the treatment of palmar plantar erythrodysesthesia
EP2114384A4 (fr) * 2007-02-15 2012-02-01 Derma Young Ltd Compositions et méthodes permettant d'améliorer l'administration transmuqueuse
EP2114384A2 (fr) * 2007-02-15 2009-11-11 Derma-Young Ltd. Compositions et méthodes permettant d'améliorer l'administration transmuqueuse
CN101754755A (zh) * 2007-02-15 2010-06-23 德尔玛-杨有限公司 促进跨粘膜递送的组合物及方法
FR2928543A1 (fr) * 2008-03-17 2009-09-18 Oreal Utilisation d'inhibiteurs de la xanthine oxydase pour la pigmentation capillaire
JP2008291032A (ja) * 2008-06-04 2008-12-04 Paoli Ambrosi Gianfranco De ケミカルピーリングのための処方
EP2246057A1 (fr) 2009-04-29 2010-11-03 Nobera Pharma, S.L. Utilisation d'allopurinol pour le traitement d'une cutiréaction sur les mains et sur les pieds
US20100280051A1 (en) * 2009-04-29 2010-11-04 Yolanda Rodemer Use of allopurinol for the treatment of hand foot skin reaction
US8623878B2 (en) * 2009-04-29 2014-01-07 Nobera Pharma, S.L. Use of allopurinol for the treatment of hand foot skin reaction
US20140080845A1 (en) * 2009-04-29 2014-03-20 Nobera Pharma, S.L. Use of allopurinol for the treatment of hand foot skin reaction
RU2543325C2 (ru) * 2009-04-29 2015-02-27 Нобера Фарма, С.Л. Применение аллопуринола для лечения ладонно-подошвенного синдрома
WO2014024193A1 (fr) * 2012-08-07 2014-02-13 Prodel Pharma Ltd. Compositions et procédés d'administration rapide, à travers les muqueuses, d'ingrédients pharmaceutiques
WO2019077521A1 (fr) * 2017-10-17 2019-04-25 Alfakjn S.R.L. Composition liquide destinée à être utilisée comme anti-inflammatoire
WO2020033666A1 (fr) * 2018-08-09 2020-02-13 Asymmetric Therapeutics, Llc Compositions et procédés de traitement des effets secondaires associés à l'administration d'agents thérapeutiques

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Publication number Publication date
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