WO2019090405A1

WO2019090405A1 - Ciclesonide medicinal product for curing and preventing flu caused by the influenza virus

Info

Publication number: WO2019090405A1
Application number: PCT/BR2018/050375
Authority: WO
Inventors: Mario Virgilio de CARVALHO JÚNIOR
Original assignee: Carvalho Junior Mario Virgilio De
Priority date: 2017-11-11
Filing date: 2018-10-15
Publication date: 2019-05-16

Abstract

The invention disclosed herein is intended for the pharmaceutical industry and the area of medicine for combating flu, and relates to any medicinal-product composition that is characterized by containing ciclesonide in the composition thereof for the purpose of producing a medicinal product for combating various forms of flu caused by the influenza type A, B and C viruses, including strains. This filing is in the form of the Swiss patent application formula. The components of the basic formulation disclosed are ethanol, distilled water, sodium chloride and ciclesonide. However, the formulation may be presented as other formulations using ciclesonide for a medicinal-product formulation composition for assisting the immune system in combating the influenza type A, B and C viruses, thereby preventing the symptoms known as flu.

Description

"CYCLESONIDE MEDICATION FOR CURE AND PREVENTION OF INFLUENZA VIRUS INFLUENZA".

TECHNICAL FIELD

The present invention is directed to the pharmaceutical industry and the field of medicine to combat influenza.

BACKGROUND OF THE INVENTION

2. There is not much to talk about the problem of influenza (physiological disturbance caused by the contamination of influenza viruses of the family Orthomyx-oviridae), which for centuries has affected the human population and still today causes the death of more than 100,000 people per year, depending on the virulence of the outbreak.

. In the United States, influenza results in approximately 200,000 hospitalizations and 36,000 deaths in a typical endemic season (Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, et al. Influenza-related mortality and respiratory syncytial virus in JAMA 2003, 289: 179-86).

. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504709/

. The preventive treatment that has been employed with relative efficiency is vaccination, from 60% to 90%, has its cons which are:

. - the production of vaccines in a period shortly before the possible outbreaks due to the changes that the virus suffers. Often one of these changes (mutation / strain variation) is not detected at the stage of vaccine development, or even, it arises after its production.

. - The vaccine still has the drawback of taking up to 30 days for the immune system to prepare for the new virus variant.

. There is no preventive treatment in the case of an immediate infection that can be submitted to a family in which one of the members contracted influenza. Or even in an office, factory or urban transport system. The general idea is "we'll all get the flu". Especially when the transmitter is a person who has been vaccinated. . In general the therapy is to take some antiallergic accompanied by a muscle relaxant. And the blessed vitamin C that no effect does on fighting manifested influenza, or more recently the Oseltamivir Phosphate in some cases when the flu is installed and recommended for type HN1.

CURRENT USE OF CICLESONIDA

10. Ciclesonide has been used to treat MIA, bronchitis, and allergic rhinitis.

11. Being marketed under two names:

12. 1 - ALVESCO: for use in asthma. As the insert is cut from the link:

13. http://www.anvisa.gov.br/datavisa/fila_bula/frm ViewBula.asp? PNuTransacao = 478222 2014 & pldAnexo = 2086734

14. WHAT IS THIS MEDICATION INDICATED FOR?

15. Alvesco ^® is a medicine for the control of asthma and prevention of future crises. It should be used regularly, even if you are not having symptoms, as directed by your doctor.

16. 2 - ONMINARIS: for use in allergic rhinitis, coryza, itch and spiro. According to the bull whose text we reproduce below.

17. http://www.takedabrasil.com/"'/media/Countries/br/Files/Bulas/Omnaris%20-%20Paciente.pdf

18. WHAT IS THIS MEDICINE INDICATED FOR?

19. This medicine is used to treat symptoms of allergic rhinitis, including stuffy nose, runny nose, itching, and sneezing.

20. These formulations are shown in patents: PI 0313611-6, PI 0312377-4

HOW THE INVENTOR HAS CAME THE MEDICINAL FORMULATION THAT CURES THE FLU

21. Having entered the fifth decade of life. Always being a flu sufferer. Affected once or twice a year, high fever and infection in the throat and lung. Knowing that after 60 years the virulence is greater and even lethal. After catching a flu I leave you 2 days of bed with no strength to stand up. Started researching on the internet, notably on the website www.ncbi.nlm.nih.gov on the virus causing, famous Influenza, its form of proliferation, infection and how the organism reacts.

22. In this research, we analyzed several types of drugs and their action. Thus he became aware of the action of antibiotics, non-steroidal anti-inflammatory drugs and steroids.

23. Steroid anti-inflammatory drugs, or corticosteroids that exerted a potent anti-inflammatory effect (glucocorticoid), became aware of the fact that its action led to the reduction of cellular multiplication. Increasing the time of its multiplication or even its self-description. They may interfere with protein synthesis or cell division as can be seen in the statement below:

24. -Reduction of growth rhythm: glucocorticoids exert significant suppressive effects throughout the somatotrophic axis. In prolonged use, they reduce pituitary growth hormone (GH) secretion and its ability to generate IGF-I at the hepatic and hepatic levels. (IGF-I), such as IGFBP1, reducing the bioavailability of IGF-I. As a final effect, there is a reduction in the local concentration of IGF-I and the action of GH on cartilage These effects are aggravated by the inhibitory action of glucocorticoids on growth cartilage, preventing the maturation of resting layer cells (GH dependent) and cell division on the proliferative layer (dependent IGF-I).

25.-Disproportionate cell killing: part of the therapeutic efficacy of glucocorticoids is due to its ability to reduce the rate of cell proliferation and induce cell death by apoptosis. This is an important mechanism to combat neoplastic cells, but such effects are non-specific and reach non-neoplastic cells as well. Such actions may be noticeable in hematopoietic cells, collagen and elastin producing cells, epidermal cells, mucosal cells of the digestive and respiratory tracts, muscle cells, etc. In this way, findings such as lymphopenia, thin and streaked skin, mucosal erosions, peripheral myopathy, dilated cardiomyopathy, etc. may be present.

26. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0021-75572007000700007 27. This inventor, by visualizing the fact that the virus installs itself inside a cell and multiplies itself by taking advantage of its DNA. Combined with the fact that the immune system begins to produce defenses after the body's contamination by the virus. Still combined with the fact that the organic defense is complete in seven days and that the recommendation of the use of corticosteroids should not be superior to this period, nevertheless, to cover this period, as below:

28. "To reduce the duration of treatment to a minimum, since treatments lasting between 5 and 7 days have few side effects and rapid recovery of the hypothalamic-pituitary axis;

It was then reasoned that some glucocorticoids could be used to slow the proliferation of the virus in the mucosa, or even by activating the enzyme. apoptosis (programmed death), giving the body time to create enough antibodies to fight infection without major problems - pain, fatigue, fever and so on.

1. He began to perform exhaustive research on glucocorticoids and their action on mucous membranes on the American Cancer Institute website. It called a special attention to him, the ciclesonida by its peculiarities below discriminated:

2. Oral bioavailability: the desirable factor in this case should be the lowest possible, since the action should be limited to mucosae of about <1% for ciclesonide and fluticasone 20-40% for beclomethasone.

3. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177893/

4. Prodrogras: Ciclesonide has even more advantage because it is a prodrug that must be activated and in the bloodstream it is not activated. This virtually eliminates its negative effect on the immune system. As will be discussed below. Ciclesonide is a prodrug that is inhaled as an inactive compound and then converted into its active metabolite (des-ciclesonide) by enzymes located in the pulmonary epithelium and mucosa in general.

5. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177893/ 6. Blood plasma behavior: When an ICS binds to plasma protein (albumin) in the systemic circulation, it becomes pharmacologically inactive. Therefore, a high degree of plasma protein binding is desirable to reduce the potential for systemic side effects. Ciclesonide is inversely correlated with degrees of cortisol suppression. It is highly protein bound (99%) in the systemic circulation resulting in minimal suppression of cortisol.

7. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177893/

8. Half-life in the bloodstream: A desirable factor is that the half-life in the bloodstream is as short as possible. Thus we have des-ciclesonide, the active metabolite of ciclesonide, with a half-life of 30 minutes.

9. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177893/

0. In the above work, the authors conclude: "Although other glucocorticoids have reported adrenal suppression, ciclesonide has not been identified as suppressive, but they believe that a safer approach would be to screen patients over 1000 ug / day for 3-6 months. " It is noted that this conclusion refers to prolonged treatments for allergic asthma, bronchitis and rhinitis. However, as adjuvant immune system therapy to combat the influenza virus, which has a period of seven days, this inventor has realized that there is complete safety in the use of ciclesonide with a dose of up to 500 mcg if necessary for 7 to 10 days. 1. Thus, this inventor performed the tests on the drug in several initial infestations in itself with the virus acquired from colleagues who had the flu, since their nasal mucosa is very sensitive to the virus. He also succeeded in combating the virus after convincing a colleague, newly infected of using ciclesonide-based medicine. 2. He then made the decision to guarantee his rights. When he met the Swiss patent formula he tried to make the present deposit request to guarantee his rights before entering the disclosure phase.

DETAILED DESCRIPTION OF THE INVENTION

3. The active ingredient used in this invention has its use authorized by ANVISA in pharmaceutical compositions in the national market for the control of allergic rhinitis, asthma and bronchitis - the Alvesco and Onminaris. As the purpose of the present patent deposit is to obtain the patent under the Swiss formula which is the use of a drug to produce a drug formulation to be employed in therapy for specific disease. We may cite as acceptable the formulations in the above-mentioned medicaments used for rhinitis, asthma and allergic bronchitis, provided that the patent rights of ciclesonide for the manufacture of a formulation for use in the treatment of influenza caused by the influenza virus and their varieties. But another proposed formulation is the one below.

4. FORMULATION OF THIS INVENTOR

5. 1 to 5 ml of ethanol. (Solvent)

6. 4 to 6 mg ciclesonide. (Pro-drug Principle)

7. 95 to 99 ml of distilled water. (Particle Excipient)

8. 1 g sodium chloride. (Suspended particulate anti-caking agent)

9. Preparation:

0. 1 The ciclesonide is agitated in ethanol until complete dissolution in temperature.

1. 2 - Sodium chloride is mixed in the distilled water until complete dissolution.

1. 3 - The ethanol / ciclesonide solution is dripped into the center of the distilled water / sodium chloride solution. The latter moving in a circular motion so that the particles formed by the precipitation of the alcoholic solution do not agglutinate and disperse to form the suspension of ciclesonide microparticles. Being able to heat the final solution to 79 ^Q C to evaporate the ethanol.

. The above preparation results in a medicated suspension of ciclesonide in the concentration between 40mcg and 60mcg.

Claims

1 - Drug formulation using the drug ciclesonide, molar mass 540,688, nr ^Q CAS 141845-82-1, for elaboration of a drug formulation for the purpose of aiding the immune system to combat influenza virus type A, B and C and strains , whose symptoms we call influenza, including as a preventive treatment in an environment with possible infection and can be expressed by the formulation below for the preparation of 100 ml of the formulation CHARACTERIZED BY having the composition, 1 ml to 5 ml ethanol, II - 4 mg to 6 mg of ciclesonide, II 95 ml to 99 ml distilled water, IV - 1 g sodium chloride.

2 - Medicinal formulation CHARACTERIZED BY using the drug ciclesonide, molar mass 540,688, nr ^Q CAS 141845-82-1, with other active products and excipients QSP, to elaborate a drug formulation with the purpose of assisting the immune system to fight against influenza A, B and C viruses and strains, whose symptoms we call influenza, including as a preventive treatment in an environment with possible infection.

A hand pump or spray dispenser CHARACTERIZED to contain the pharmaceutical composition of claim 1 or 2 for purposes of use in anti-influenza A, B, C and anti-virus therapy.

Another type of dispenser for use in inhalers is characterized by containing composition according to claim 1 or 2 for use in anti-influenza A, B, C and anti-virus therapy.

5. A composition comprising the substances of claim 1, items I, II, II and IV for the purpose of being employed in therapy to assist the immune system in combating the influenza virus and its influenza-causing strains. - Formulation CHARACTERIZED as constituting the substances of claim 1, items I, II, II and IV.

- Use of ciclesonide drug, molecular weight 540.688, ^Q nr CAS 141845-82-1, to be used for the preparation of a drug characterized by containing ciclesonide in combination with other principles and excipients QSP to treat influenza disease caused by influenza virus , and its strains, as well as in the auxiliary immune system therapy to combat influenza A, B and C viruses and strains, including as a preventive therapy, in an environment with possible infection by the influenza virus and its strains.