DE102020002349A1 - Combination, can be used for the treatment and prophylaxis of corona virus-induced lung dysfunction and damage - Google Patents
Combination, can be used for the treatment and prophylaxis of corona virus-induced lung dysfunction and damage Download PDFInfo
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- DE102020002349A1 DE102020002349A1 DE102020002349.5A DE102020002349A DE102020002349A1 DE 102020002349 A1 DE102020002349 A1 DE 102020002349A1 DE 102020002349 A DE102020002349 A DE 102020002349A DE 102020002349 A1 DE102020002349 A1 DE 102020002349A1
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Abstract
Die Erfindung bezieht sich auf eine Kombination zur Prophylaxe und/oder Behandlung von insbesondere Corona-Viren-induzierter Lungendysfunktion und - schäden, die A) ein Antikoagulationsmittel sowie Zusätze, ausgewählt aus üblichen Excipientien, Lösemittel und Extendern aufweist, die bei einer bevorzugten Ausführungsform auch einen Gehalt an b) einem oder mehreren Entzündungshemmern aufweisen kann.The invention relates to a combination for the prophylaxis and / or treatment of, in particular, corona virus-induced lung dysfunction and damage, comprising A) an anticoagulant and additives selected from customary excipients, solvents and extenders, which in a preferred embodiment also have one Content of b) one or more anti-inflammatory agents.
Description
Die Erfindung betrifft eine Kombination, einsetzbar zur Behandlung und Prophylaxe Corona-Viren-induzierter Lungendysfunktion und - schädenThe invention relates to a combination which can be used for the treatment and prophylaxis of corona virus-induced lung dysfunction and damage
Coronaviren, wie Sars-Cov-2 und Covid 19 oder MERS-Cov führen häufig zu Lungenentzündungen, die eine starke Einschränkung und sogar Schädigung der Lunge bewirken, wodurch aufwändige Behandlungen und in besonders gravierenden Fällen sogar Beatmung mit Beatmungsgeräten eingesetzt werden muss.Coronaviruses such as Sars-Cov-2 and Covid 19 or MERS-Cov often lead to pneumonia, which severely restrict and even damage the lungs, which means that complex treatments and, in particularly serious cases, even ventilation with ventilators have to be used.
Dabei treten in einigen Fällen Lungenembolien mit Verbrauch von Antithrombin und Bildung von Anti-Phospholipid-Antikörpern (APA) auf. APA fördern die Bildung von Thromben. Die schwere Form führt zum Tod durch eine Embolie.In some cases, pulmonary embolism occurs with consumption of antithrombin and the formation of anti-phospholipid antibodies (APA). APAs promote the formation of thrombi. The severe form leads to death from an embolism.
Es ist bekannt, den Entzündungshemmer Chloroquin alleine zur Behandlung von Corona einzusetzen - die Erfolge waren aber eher mäßig.It is known to use the anti-inflammatory drug chloroquine alone to treat corona - but the success has been rather moderate.
Es ist daher Aufgabe der Erfindung, eine Kombination zu schaffen, welche Lungenfunktionsstörungen bei Coronainfektionen vermeidet oder verringert.It is therefore the object of the invention to create a combination which avoids or reduces lung dysfunction in corona infections.
Die Aufgabe wird durch eine Kombination mit den Merkmalen des Anspruchs 1 gelöst. Vorteilhafte Weiterbildungen ergeben sich aus den abhängigen Ansprüchen.The object is achieved by a combination with the features of claim 1. Advantageous developments result from the dependent claims.
Ferner bezieht die Erfindung sich auch auf ein Verfahren zur Herstellung der Kombination.The invention also relates to a method for producing the combination.
Grundsätzlich weist die Kombination zur Behandlung und Prophylaxe Corona-Viren-induzierter Lungendysfunktion und - schäden, A) ein Antikoagulationsmittel sowie Zusätze, ausgewählt aus üblichen Excipientien, Lösemittel und Extendern auf.In principle, the combination for the treatment and prophylaxis of corona virus-induced lung dysfunction and damage, A) an anticoagulant and additives selected from the usual excipients, solvents and extenders.
Es kann vorteilhaft sein, in der Kombination auch B) mindestens ein antiinflammatorisches Mittel wie Chloroquin, Chinin oder Hydrochloroquin, Boswelliaextrakte und deren Abkömmlinge und Derivate und/oder Enzyme einzusetzen.It can be advantageous to use in the combination also B) at least one anti-inflammatory agent such as chloroquine, quinine or hydrochloroquine, boswellia extracts and their derivatives and derivatives and / or enzymes.
Die Erfindung bezieht sich auch auf eine Zusammensetzung, die durch Mischung von mehreren der in der Kombination vorliegenden Komponenten erhältlich ist als Kombination zur Prophylaxe und Behandlung von insbesondere durch Corona-Viren-induzierter Lungendysfunktion und - schäden,The invention also relates to a composition which can be obtained by mixing several of the components present in the combination as a combination for the prophylaxis and treatment of lung dysfunction and damage, in particular caused by corona virus,
Bei Befall oder drohendem Befall (Prophylaxe bei einer Epidemie) mit COVID 19, Sars-Cov-2 oder MERS-Cov wird daher gegen das Auftreten einer eingeschränkten Lungenfunktion - erkennbar bspw. durch Husten oder Atemnot, erfindungsgemäß umgehend eine Antikoagulation mit einem Antikoagulationsmittel, das ggf. infiltriert oder oral gegeben wird - wie Heparin, Danaparoid, Hirudin, Warfarin, Phenprocoumon, Acenocumarol und/oder durch orale Gabe von „Direkte Orale Antikoagulantia“ (DOAKs, wie Dabigatran, Rivaroxaban, Apixaban, Edoxaban) oder entsprechende Enzyme wie Bromelain, Papain, Nattokinase etc. vorgenommen. Dies kann bereits prophylaktisch Schlimmeres abschwächen oder verhindern.In the event of an infestation or threat of infestation (prophylaxis in the event of an epidemic) with COVID 19, Sars-Cov-2 or MERS-Cov, an anticoagulation with an anticoagulant is immediately used according to the invention to counteract the occurrence of a restricted lung function - recognizable e.g. by cough or shortness of breath if necessary infiltrated or given orally - such as heparin, danaparoid, hirudin, warfarin, phenprocoumon, acenocumarol and / or by oral administration of "direct oral anticoagulants" (DOAKs, such as dabigatran, rivaroxaban, apixaban, edoxaban) or corresponding enzymes such as bromelain, Papain, nattokinase etc. made. As a prophylactic measure, this can attenuate or prevent worse.
Eine erfindungsgemäße Kombination von Antikoagulantien mit ggf. weiteren Wirkstoffen, wie antiinflammatorisch wirkenden Stoffen als injizierbare Zubereitung hat wiederum den Vorteil, dass sie schnell vom Körper aufgenommen wird und exakt individuell vor Ort dosiert werden kann. Sie ist vor allem in akuten Fällen indiziert.A combination according to the invention of anticoagulants with possibly other active ingredients, such as anti-inflammatory substances as an injectable preparation, in turn has the advantage that it is quickly absorbed by the body and can be dosed precisely and individually on site. It is particularly indicated in acute cases.
Es kann aber auch günstig sein, dass das erfindungsgemäße Mittel mit Antikoagulantien für orale Gabe formuliert ist. Dadurch kann bspw. der Aufwand für medizinische Eingriffe durch Fachpersonal, wie Injektionen, vermieden werden und auch in einfacher Weise eine Vorratshaltung betrieben werden. Die oral verabreichbare Form kann leicht (auch von unqualifizierten Personen) in entsprechend verringerter Dosis als Prophylaxe bei einer drohenden Ansteckung verabreicht werden, benötigt aber aufgrund der notwendigen Aufnahme im Verdauungstrakt länger zum Erreichen der therapeutisch wirksamen Menge im Lungengewebe.However, it can also be favorable that the agent according to the invention is formulated with anticoagulants for oral administration. In this way, for example, the expenditure for medical interventions by specialist personnel, such as injections, can be avoided and storage can also be carried out in a simple manner. The orally administrable form can easily (even by unqualified persons) be administered in a correspondingly reduced dose as prophylaxis in the event of an impending infection, but it takes longer to reach the therapeutically effective amount in the lung tissue due to the necessary absorption in the digestive tract.
Je nach den Bedingungen wird daher eine orale oder infiltrierende Gabe sinnvoller sein.Oral or infiltrating administration will therefore make more sense, depending on the conditions.
In den Fällen, in denen Entzündungen und damit auch häufig Schädigungen des Lungengewebes auftreten, ist es sinnvoll, der erfindungsgemäßen Kombination NSAID (non-steroidal-antiinflammatory drug) Entzündungshemmer, wie Boswellia-Extrakte, Teufelskrallezubereitungen und Curcumazubereitungen; 4-Amino-chinoline, wie Hydrochloroquin, Chloroquin oder Chinin sowie deren Derivate, Salze und Abkömmlinge gleichzeitig mit dem Antikoagulationsmittel oder verzögert zu diesem, zuzusetzen.In those cases in which inflammation and thus frequent damage to the lung tissue occur, it makes sense to use the combination according to the invention NSAID (non-steroidal anti-inflammatory drug) anti-inflammatory agents, such as Boswellia extracts, devil's claw preparations and turmeric preparations; 4-Amino-quinolines, such as hydrochloroquine, chloroquine or quinine and their derivatives, salts and derivatives, to be added simultaneously with the anticoagulant or with a delay in relation to it.
Ggf. kann die Kombination in gravierenden Fällen ergänzt sein durch eine infiltrierbare Lösung von Humanplasma mit Corona-Antikörpern und/oder autologe mesenchymale Stammzellen, bevorzugt aus Fettgewebe. Die Antikörper können zunächst einen Teil des Immunsystems entlasten.If necessary, the combination can be supplemented in serious cases by an infiltratable solution of human plasma with corona antibodies and / or autologous mesenchymal stem cells, preferably from adipose tissue. The antibodies can initially relieve part of the immune system.
Die mesenchymalen Stammzellen können bei der Heilung bzw. Regeneration des durch Entzündungen und Intoxikation geschädigten Lungengewebes unterstützend wirken, denn Corona bewirkt in manchen Fällen eine schwere Schädigung der Lungenzellen, die so therapiert werden können .The mesenchymal stem cells can support the healing or regeneration of the lung tissue damaged by inflammation and intoxication, because in some cases Corona causes severe damage to the lung cells, which can be treated in this way.
Die Dosis der erfindungsgemäßen Kombination sowie der darin enthaltenen Wirkstoffe sowie das Mischungsverhältnis der Einzelkomponenten kann entsprechend dem vorliegenden Krankheitsbild adaptiert werden.The dose of the combination according to the invention and of the active ingredients contained therein and the mixing ratio of the individual components can be adapted according to the clinical picture at hand.
Bei Patienten, die durch eine Vorerkrankung gefährdet sind oder sich Coronaviren aussetzen müssen, kann eine geringere Dosis als Hochrisikoprophylaxe bei Patienten, die noch keine oder nur geringe Symptome aufweisen - dienen. Diese kann bis zur therapeutischen Dosis, jeweils nach dem klinischen Zustand, entsprechend den an sich bekannten Methoden zur Blutgerinnungstestung, angepasst werden. Bei Antithrombinmangel sollte dieser ausgeglichen werden. Falls Anti-Phospholipid-Antikörper gebildet werden, können diese durch eine geeignete Dosis des Entzündungshemmers im Mittel, bspw. 400mg -800mg Hydrochloroquin, täglich behandelt werden, auch um die Antikoagulationsmittel-Dosis zu stabilisieren oder zu reduzieren.For patients who are at risk from a previous illness or who have to expose themselves to coronaviruses, a lower dose can serve as a high-risk prophylaxis for patients who have no or only few symptoms. This can be adjusted up to the therapeutic dose, in each case according to the clinical condition, in accordance with the methods known per se for blood coagulation testing. If there is a lack of antithrombin, this should be compensated for. If anti-phospholipid antibodies are formed, they can be treated daily with a suitable dose of the anti-inflammatory agent, e.g. 400 mg -800 mg hydrochloroquine, also to stabilize or reduce the anticoagulant dose.
Die Schädigung von Geweben, insbesondere des Lungengewebes durch das Virus kann durch die Transfusion von Humanplasma mit Coronavirus Antikörpern (Plasma von Personen, die nach einer Infektion genesen sind), das virusinaktiviert ist, reduziert oder sogar verhindert werden.The damage to tissues, especially lung tissue, caused by the virus can be reduced or even prevented by transfusing human plasma with coronavirus antibodies (plasma from people who have recovered from an infection) that is virus-inactivated.
Alternativ oder ergänzend kann eine eventuelle Lungenschädigung mit autologen mesenchymalen Stammzellen, die aus Fettgewebe gewonnen und expandiert wurden, per intravenöse Applikationen zumindest gebessert oder sogar geheilt werden.Alternatively or in addition, possible lung damage with autologous mesenchymal stem cells, which were obtained from adipose tissue and expanded, can at least be improved or even cured by intravenous applications.
Nachfolgend wird die Erfindung näher anhand von Behandlungsprotokollen näher erläutert, wobei der Schutzumfang keineswegs auf dieselben eingeschränkt ist. Die Behandlungen mit Stammzellen und Plasma sind dem Fachmann bekannt und können zusätzlich erfolgen, wenn notwendig.The invention is explained in more detail below on the basis of treatment protocols, the scope of protection being in no way restricted to the same. The treatments with stem cells and plasma are known to the person skilled in the art and can also be carried out if necessary.
Behandlung Patient 1 - Verhinderung LungenembolieTreatment patient 1 - prevention of pulmonary embolism
Ein 68-jähriger Mann mit arterieller Hypertonie und Diabetes mellitus und einem BMI von 30 sowie einem viral induzierten APA Syndrom, das typisch für Corona-Viren ist, wird nach drei Lungenembolien auf Dauermedikamention mit 7,5 mg Warfarin (Coumadin®) (INR 1,8 - 2,4)/Tag in Kombination mit 3 x 200 mg Hydrochloroquin (Plaquenil ® - von Sanofi-Aventis)/Tag und 100 mg Nattokinase (von SinoPlaSan)/Tag behandelt. Unter dieser Medikation traten in den letzten 10 Jahren keine weitere Lungenembolien oder Thrombosen mehr auf.A 68-year-old man with arterial hypertension and diabetes mellitus and a BMI of 30 as well as a virally induced APA syndrome, which is typical for corona viruses, is given 7.5 mg warfarin (Coumadin®) (INR 1 , 8 - 2.4) / day in combination with 3 x 200 mg hydrochloroquine (Plaquenil ® - from Sanofi-Aventis) / day and 100 mg nattokinase (from SinoPlaSan) / day. No further pulmonary embolism or thrombosis occurred with this medication in the last 10 years.
Behandlung Patient 2Treatment of patient 2
Eine 42 jährige normalgewichtige Frau mit Antithrombinmangel und rezidivierenden viralen Mund-Rachen Infektionen - unter anderem mit dem SARS-Virus - mit zwei Thrombosen und Lungenembolien wird mit 110 mg Dabigatan 2x täglich und 3x 1000 FIP-Einheiten/Tag Bromelain (Bromelain-POS® -Ursapharm) dauerbehandelt. Seitdem ist keine Thrombose oder Lungenembolie aufgetreten.A 42-year-old woman of normal weight with antithrombin deficiency and recurrent viral mouth and throat infections - including the SARS virus - with two thromboses and pulmonary embolisms is given 110 mg dabigatan twice a day and 3x 1000 FIP units / day bromelain (Bromelain-POS® - Ursapharm) permanently treated. No thrombosis or pulmonary embolism has occurred since then.
Während Ausführungsbeispiele beschrieben wurden, sollen sie mögliche Formen beschreiben, die durch die Ansprüche umfasst sind. Die in der Beschreibung verwandten Worte sind rein beschreibend und nicht beschränkend und es versteht sich, dass verschiedenste Änderungen vorgenommen werden können, ohne vom Geist und Umfang der Offenbarung abzuweichen. Wie beschrieben, können die Merkmale verschiedener Ausführungsbeispiele kombiniert werden, um weitere Ausführungsbeispiele der Erfindung zu bilden, die nicht explizit beschrieben oder dargestellt sein können. Während verschiedene Ausführungsbeispiele zur Bereitstellung von Vorteilen oder Vorteilen gegenüber anderen Ausführungsbeispielen oder Implementierungen des Stands der Technik in Bezug auf eine oder mehrere gewünschte Eigenschaften beschrieben worden sind, erkennt der Fachmann, dass ein oder mehrere Merkmale geändert werden können, um gewünschte allgemeine Systemattribute, die von der spezifischen Anwendung und Implementierung abhängen, zu erzielen. Diese Attribute können Kosten, Transport- und Lagerfähigkeit, Lebenszykluskosten, Marktfähigkeit, Aussehen, Verpackung, Größe, Gebrauchstauglichkeit, Gewicht, Herstellbarkeit, die Verabreichungsvereinfachung usw. einschließen.While exemplary embodiments have been described, they are intended to describe possible forms encompassed by the claims. The words used in the description are purely descriptive and not restrictive, and it is understood that various changes can be made without departing from the spirit and scope of the disclosure. As described, the features of different exemplary embodiments can be combined in order to form further exemplary embodiments of the invention that cannot be explicitly described or illustrated. While various embodiments have been described to provide advantages or advantages over other embodiments or implementations of the prior art with respect to one or more desired properties, those skilled in the art will recognize that one or more features can be changed to achieve desired general system attributes derived from depend on the specific application and implementation. These attributes can include cost, portability and storability, life cycle cost, marketability, appearance, packaging, size, usability, weight, manufacturability, ease of administration, and so on.
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| PCT/DE2021/100353 WO2021213587A1 (en) | 2020-04-19 | 2021-04-16 | Combination which can be used for the treatment and prophylaxis of coronavirus-induced pulmonary dysfunction and damage |
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Non-Patent Citations (5)
| Title |
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| Agnelli G. u.a.: Anticoagulant treatment for acute pulmonary embolism: a pathophysiology-based clinical approach. In: European Respiratory Journal, 45, 2015, 1142 - 1149. https://erj.ersjournals.com/content/45/4/1142.long |
| Li T. u.a.: Clinical observation and management of COVID-19 patients. In: Emerging Microbes & Infections, Vol. 9, 2020, 687 - 690. https://doi.org/10.1080/22221751.2020.1741327 |
| Siebenlist D. u.a.: Flottierender rechtsatrialer Thrombus als Ursache rezidivierender Lungenembolien. In: Dtsch. Med. Wschr. , 115, 1990, 1754 - 1757. |
| Tang N. u.a: Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. In: Journal of Thrombosis and Haemostasis, Vol. 18, 2020, 5, 1094 - 1099. https://doi.org/10.1111/jth.14817 |
| Yamamoto M. u.a.: Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Array. In: Antimicrobial Agents and Chemotherapy, Vol. 60, Nov. 2016, 11, 6532 - 6539. https://aac.asm.org/content/60/11/6532.long |
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