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WO2022053108A1 - Glucocorticoïde destiné à être utilisé dans la prophylaxie d'un sdra - Google Patents

Glucocorticoïde destiné à être utilisé dans la prophylaxie d'un sdra Download PDF

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Publication number
WO2022053108A1
WO2022053108A1 PCT/DE2021/100749 DE2021100749W WO2022053108A1 WO 2022053108 A1 WO2022053108 A1 WO 2022053108A1 DE 2021100749 W DE2021100749 W DE 2021100749W WO 2022053108 A1 WO2022053108 A1 WO 2022053108A1
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WO
WIPO (PCT)
Prior art keywords
glucocorticoid
ards
use according
daily dosage
patients
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/DE2021/100749
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German (de)
English (en)
Inventor
Rainer MERK
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Individual
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Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to DE112021004780.9T priority Critical patent/DE112021004780A5/de
Publication of WO2022053108A1 publication Critical patent/WO2022053108A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses

Definitions

  • Glucocorticoid for use in the prophylaxis of ARDS
  • the present invention relates to the use of a glucocorticoid in the prophylaxis of ARDS when infected with an ARDS-inducing virus.
  • the pandemic triggered by the worldwide outbreak of the respiratory disease COVID-19 has triggered extensive research activities regarding the treatment and prophylaxis of this disease. While the disease often presents as a mild respiratory infection, some patients develop pneumonia, usually in the second week of illness, which can progress to acute respiratory failure (Acute Respiratory Distress Syndrome; ARDS), which is often fatal.
  • ARDS acute Respiratory Distress Syndrome
  • the inflammatory reaction of the lungs represents the body’s own defense reaction to damage to the alveoli by SARS-CoV-2 viruses. If this defense reaction is increased (hyperergic), a cytokine storm is initiated, which results in a virus-induced anaphylactoid immune response .
  • the Robert Koch Institute sees patients with a weakened immune system as a risk group for a severe course of COVID-19 disease due to the regular intake of medication that can influence and reduce the immune system, such as cortisone.
  • This prophylaxis should be based on the use of a drug that has been tried and tested for a long time, so that its new medical indication can be approved quickly and, based on the experience already available about the risks and side effects of the drug, a high level of acceptance of this prophylactic method can be expected .
  • a glucocorticoid for use in the prophylaxis of ARDS infections with a ARDS-inducing virus by administration prior to the time of infection.
  • the glucocorticoid can also be used to prevent other complications of such an infection that occur alongside ARDS, such as cardiovascular diseases and kidney diseases.
  • the invention is based on the finding that gentle immune modulation at the time a COVID-19-1 infection can prevent an anaphylactoid immune response. The invention therefore does not serve to protect against a viral infection, but rather to protect against a hyperergic defense reaction of the immune system to the viral infection.
  • the administration preferably takes place once or several times a day over a period of at least 2 weeks before the time of infection, so that there is already ongoing immune modulation upon contact with the ARDS-inducing virus.
  • the suppression of the immune system provided according to the invention delays virus elimination. With successful prophylaxis of ARDS, however, this is not only harmless, but also has the additional advantage that herd immunity in the population can be achieved more quickly. If the proportion of severe disease progressions with the occurrence of ARDS could be reduced by 95% using glucocorticoids, for example, the healthcare system could tolerate twenty times the current daily infection numbers. With up to 600,000 new infections per day, it would be possible in Germany, for example, to achieve herd immunity within 80 days.
  • the glucocorticoid can be used for the manufacture of a medicament which is intended in particular for oral administration.
  • Glucocorticoids for oral use have been tried and tested for a long time and their risks and side effects are therefore well known.
  • Glucocorticoids promote the conversion of proteins into glucose and glycogen in the glucose metabolism. Both a naturally occurring glucocorticoid and an artificial glucocorticoid can be used for the prophylaxis according to the invention.
  • the glucocorticoid is preferably selected from the group which, in addition to the natural glucocorticoids cortisone and hydrocortisone, also contains the artificial glucocorticoids cloprednol, fluocortolone, betamethasone, dexamethasone, paramethasone, prednisone, prednisolone, methylprednisolone and triamcinolone.
  • a mixture of several giucocorticoids from this group can also be used to produce a combined preparation.
  • glucocorticoids are prednisone, prednisolone, methylprednisolone and mixtures thereof, which are particularly well tolerated due to their short biological half-life.
  • the glucocorticoid is very particularly preferably prednisolone.
  • giucocorticoids Long-term use of high doses of giucocorticoids can reach such a high concentration in the blood that they trigger what is known as Cushing's syndrome. This initially manifests itself in an elevated blood sugar level and develops with increased accumulation of fatty tissue on the trunk and simultaneous muscle atrophy on the limbs.
  • use is preferably by daily dosing below the Cushing's threshold dose of the glucocorticoid.
  • the Cushing's threshold dose is a value of the daily dosage tabulated in the specialist literature for all glucocorticoids that is just not supposed to trigger Cushing's syndrome.
  • the adult Cushing's threshold dose for the preferred glucocorticoids is given in Table 1:
  • a different Cushing threshold dose should be used for children.
  • the use be limited to a daily dosage below 80% of the Cushing's threshold dose of the glucocorticoid is used to ensure even greater prophylactic safety. Furthermore, it is preferred that the use takes place through a daily dosage which has a relative glucocorticoid effect which corresponds to a daily dosage in the range from 15 mg to 25 mg hydrocortisone. It particularly preferably corresponds to a daily dosage of 20 mg hydrocortisone. Different natural glucocorticoids and different artificial glucocorticoids have different relative glucocorticoid effects.
  • the relative glucocorticoid activity of the preferred glucocorticoids is listed in Table 2.
  • the relative glucocorticoid effects of other glucocorticoids as well as their Cushing threshold doses can be found in the Roche Medical Lexicon, for example.
  • prednisolone is used as the glucocorticoid, which has a relative glucocorticoid effect of 4.0 in relation to hydrocortisone
  • the preferred daily dose for prophylaxis is therefore 5 mg.
  • Only a few severe courses of COVID-19 diseases in infected people under the age of 45 are known. This suggests that around 1975 there was already a pandemic with the SARS-CoV-2 virus or a very similar ARDS-inducing corona virus. This pandemic presumably had a very low virulence and was therefore not perceived by the public as a pandemic.
  • the memory cells of the immune system would recognize the SARS-CoV-2 virus as equivalent to the ARDS-inducing coronavirus of the time.
  • the cytokine storm would be initiated, resulting in a virus-induced anaphylactic reaction.
  • Such an infection process would be comparable to that of the Spanish flu, for example.
  • patients up to 20 years old who had a first contact with the virus were only mildly affected, 20 to 40 year old patients who had already been exposed to a second contact were severely affected and patients over 40 years old who had been exposed to a third contact were, in turn, mildly affected.
  • the glucocorticoid should be particularly suitable for use in the prophylaxis of ARDS in patients aged at least 40 years, in particular at least 45 years, since there is a high probability of severe courses of the to be able to prevent illness.
  • various exemplary embodiments of the invention provide for prophylactic treatments to prevent a severe course of any COVID-19 disease that may occur.
  • a medication containing a glucocorticoid in the daily dose given in Table 5 is taken orally every day. It is taken even before a COVID-19 infection occurs and in this way gives the patient protection against a severe course of the disease should he become infected with the SARS-CoV-2 virus.
  • tablets containing 5 mg prednisolone are available from numerous manufacturers and could be used for the new medical indication described here.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Virology (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un glucocorticoïde qui peut être utilisé dans la prophylaxie d'un SDRA en cas d'infection par un virus induit par le SDRA par administration avant la date d'infection.
PCT/DE2021/100749 2020-09-12 2021-09-10 Glucocorticoïde destiné à être utilisé dans la prophylaxie d'un sdra Ceased WO2022053108A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE112021004780.9T DE112021004780A5 (de) 2020-09-12 2021-09-10 Glucocorticoid zur Verwendung bei der Prophylaxe eines ARDS

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE102020005589 2020-09-12
DE102020005589.3 2020-09-12
DE2021100099 2021-02-02
DEPCT/DE2021/100099 2021-02-02

Publications (1)

Publication Number Publication Date
WO2022053108A1 true WO2022053108A1 (fr) 2022-03-17

Family

ID=77774647

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2021/100749 Ceased WO2022053108A1 (fr) 2020-09-12 2021-09-10 Glucocorticoïde destiné à être utilisé dans la prophylaxie d'un sdra

Country Status (2)

Country Link
DE (1) DE112021004780A5 (fr)
WO (1) WO2022053108A1 (fr)

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
BANI-SADR FIROUZÉ ET AL: "Corticosteroid therapy for patients with COVID-19 pneumonia: a before-after study", INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, ELSEVIER, AMSTERDAM, NL, vol. 56, no. 2, 4 July 2020 (2020-07-04), XP086234701, ISSN: 0924-8579, [retrieved on 20200704], DOI: 10.1016/J.IJANTIMICAG.2020.106077 *
BOGLIONE LUCIO ET AL: "The proper use of corticosteroids for 2019-nCov pneumonia: Towards promising results?", JOURNAL OF INFECTION, ACADEMIC PRESS, LONDON, GB, vol. 82, no. 1, 5 August 2020 (2020-08-05), XP086459616, ISSN: 0163-4453, [retrieved on 20200805], DOI: 10.1016/J.JINF.2020.08.001 *
FIROUZE BANI-SADR ET AL.: "Corticosteroid therapy for patients with COVID-19 pneumonia: a before-after study", INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, vol. 56, 2020, pages 106077, XP086234701, DOI: 10.1016/j.ijantimicag.2020.106077
LUDO BOGLIONE: "The proper use of corticosteroids for 2019-nCov pneumonia: Towards promising results?", JOURNAL OF INFECTION, vol. 82, 2021, pages e6 - e7
NATURE, 2020, pages 430 - 436
WANG YIN ET AL: "Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China", MEDRXIV, 12 March 2020 (2020-03-12), XP055805018, Retrieved from the Internet <URL:https://www.medrxiv.org/content/medrxiv/early/2020/03/12/2020.03.06.20032342.full.pdf> [retrieved on 20210517], DOI: 10.1101/2020.03.06.20032342 *
YIN WANG ET AL.: "Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVI D-1 9 pneumonia: single-center experience from Wuhan, China", MEDRXIV

Also Published As

Publication number Publication date
DE112021004780A5 (de) 2023-08-31

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