TAG ELDIN MOHAMED AWAD (EG)
TAG ELDIN MOHAMED AWAD (EG)
| WO1995031479A1 | 1995-11-23 | |||
| WO2004000266A1 | 2003-12-31 | |||
| WO2001049260A2 | 2001-07-12 |
| EP1314436A1 | 2003-05-28 | |||
| US5972331A | 1999-10-26 |
| Claims What is claimed is: 1. The invitation is a physiochemical product to be administered by inhalation, spray, nebulization or any other pharmaceutical ways of administration. The particle size of the sprayed material should not be less than 20 micros. 2. The method in claim 1 wherein the first pharmaceutical component is a physiological solution of sea salt (sodium chloride) at a pH ranging from 7.9 to 5.8. 3. The method in claim 1 wherein the claim 2 the second pharmaceutical component is in the form of a polymer of polysaccharide nature with particle size ranging from 0.2 to 1.0 micron. 4. The method in claim 1 wherein the claim 2, the sea salt solution (sodium chloride solution) includes a phosphate buffer with pH raining from 7.9m to 5.8. 5. The method in claim 1 wherein the claim, 3 is the polymer (polysaccharide) which has the property of merging with the mucous layers lining the ciliated endothelium lining the upper respiratory tract which has to be protected. 6. The method in claim 1 wherein interferon alpha or beta or any other suitable material whether immunological, chemical, biological, or botanical can be added. Also a protein or polypeptide from animal, botanical or human origin could be included. These alternative components could be use solely or in addition to the cytokine to initiate an innate immune response. 9 7. The method in claim 1 provides a therapeutic or protective pharmaceutical product to be administered through the nose, mouth or any other mucous membranes in the body via drops, spray, nebulization, and atomization or even with other methods as intra-dermal, subcutaneous, intramuscular or intravenous administration on condition it is dissolved in the appropriate medium. 8. The method in claim 1 wherein allows the addition of any biological, chemical, botanical or human material capable of activating the innate immune system. 9. The method in claim 8 interferon with all its strains or any other immunological, biological or natural material can be used. 10. The method in claim 8 any material, whether immunological or not could be used or added, has to be protected. 10 |
of Viral/ Microbial Infection.
Technical Field
Pharmaceutical Product for Treatment & Prophylaxis of Viral/ microbial Infection.
Background Art:
The immune system is considered to be the fundamental guard protecting the body against many diseases (if not all of them) e.g. Influenza which is a common disease worldwide affecting human, animals and birds.
Recently the influenza virus H1N1, as well as or other more virulent and dangerous strains has been developing e.g. H 5 N 1( which spreads
worldwide in a pandemic form. Recently Corona-virus infection has emerged, which has a high mortality rate ranging from 30 to 50% of those attending the intensive care units (ICs).
As there is no effective remedy for such diseases the WHO preventive measures were the only measure to control such epidemics.
Recently, in 2012 a new strain of Corona-virus, affected human subjects in Saudi Arabian and to some extent in the Gulf area. It is named Middle East Respiratory Syndrome (MERS) Corona virus infection. It is a very virulent virus with 50% mortality rate (in I.Cs) where the patients suffer from acute viral pneumonia which is difficult to cure. In fact there are many other infectious diseases and neoplasms which develop as a result of deficient immune status.
In the 1960s the Soviet Union Scientists tried to use interferon alpha in very large doses "around millions and many thousands units (I.U.)", to control and treat influenza, but the outcome was not encouraging. In the 1970s the USA, some European countries (France, UK, Germany and other) as well as Japan, China started to use relatively smaller doses, but again the outcome was not satisfactory to put it as a standard treatment for influenza infection.
The problem and the defects:
The immune system is responsible for defense against infectious diseases as influenza, as well as the development of some neoplasms.
The first stage in combating infections come through specialized peripheral cells (Dendritic cells "DC" and Antigen Processing cells "APC") which are scattered in between the mucous membrane cells lining the internal organs e.g. respiratory tract, gastrointestinal tract, urogenital tract as well as in between the coetaneous cells (Dermis).
In case of influenza infection, the peripheral immune cells (DC & APC) are scattered along the mucous membrane of the upper respiratory tract namely the nose, nasopharynx, pharynx, larynx, trachea and bronchi. Any virus infection usually interacts with the receptors of these DC & APCs. The influenza virus which spreads from one person to another through droplet infection, or by hands or handling infected material. In this case, the DCs and APCs receptors will interact with the virus and active of such cells will start the ignition of a cascade signals through the immune system. This interaction between the virus or microorganism and the DCs & APCs is nonspecific one.
Once the APCs are activated they in turn activate the CD4 immune cells; ThO and Thl which is turn secrete cytokines to activate the natural killer cells (NK cells). These activated NK cells secret interferon gamma as well as interferon alpha and beta, which attack the invading virus and
accordingly terminate the infection.
This preliminary stage of immunity is named Innate Immune Reaction (response) without identifying the type or nature of the invading micro organism. It is the frontier of defense in the body.
The new strain of viruses is more virulent and could bypass this primary phase of immunity and attack directly the pulmonary alveoli inducing acute viral pneumonia which is somewhat difficult to control. This occurs usually on the six day of infection where the signs and symptoms in these 6 days are very mild or are not recognized. This type of viruses is usually very virulent and count to 50% mortality rate.
For these above reasons, one has to develop means to activate the innate immune system to counteract this serious infection from the early beginning.
Interferon alpha has been known for over 40 years to be are antiviral immune agent and in the meantime it can activate the innate immune system, via its interactions with the receptors on the dendrite of the APCs. Which are scattered in-between the epithelial cells of the mucous membrane of the upper respiratory tract.
This innate immune reaction precedes the following stage of immune response which is a more specific one involving Th 2 & CD 8 cells. The immune cells recognize the strain of the virus, or microbes via the memory cells.
This specific immune response is named adaptive immune response where antibody formation and activation of the macrophages start to attack the invading organism in a very specific way.
In the light of this phenomena, some studies took place to estimate (detect) the effect of interferon alpha in activating the immunity of the patients, allowing I FN alpha to activate the mucosal lining of the upper respecting tract (namely nose, mouth, pharynx, nasopharynx, trachea & bronchia) by nasal drops or by inhalation via nebulization or spray via atomizers. These trials which were leaded by the Soviet Union scientists as well as other carried on by the USA, Europe & Fare East failed to control such infection particularly during epidemics. The adequate dose of interferon, as well as the type of solvent (vehicle) and its composition could be the cause of these defects. All such trials were not effective to contact the virulent strains of influenza as well as the Corona virus infection, which induces ERS Corona-virus infection where the mortality rate is up to 50% of these admitted in the ICs of hospitals.
Disclosure Of Invention :
Interferon alpha being an activator to the innate immune response in the body has been selected in an adequate concentration to allow activation of such system when sprayed into the upper respiratory tract. determination of interferon alpha, interferon gamma and interferon 2 which were assayed by ELIZA ASSAY METHODS using SIGMA standards for assay and were kept at -80C till time of assay.
At the end of day 5 (beginning of day 6) all the animals were sacrificed under anesthesia and autopsy was done.
Gross pathological examination of all organs and tissues of each animal was done. The major important organs had been exited for and were kept in saline formalin solution. These organs are; the heart, kidney, liver, thymus, suprarenale, pancreas and testicles. The respiratory tract was given a special attention, where the nose and nasopharynx were (sliced in a way to expose such tissues for histopathological examination, pharynx, larynx, trachea, bronchi and lung parenchyma.
These tissues and organs were examined by gross pathological
examination and histopathological where the times were stained by haematoxilin and eosin.
All the results were analyzed statically using the "t-student test and
AN OVA".
The amount of interferon gamma released in the circulation of the rats after exposure to natural interferon alpha nebulization with different doses in considered being the result of activation of the minute immune system.
Results & Discussion
In our experiment, it has been found that FN alpha (interferon gamma) has almost doubled in animal exposed to 500 and 1000 I.U ml of interferon alpha.
7 The rise of interferon gamma in a dose of 500 lU/ml was 205% increase, and that for 1000 lU/ml was 222%.
There was no side effects neither clinically, serologically, grace
pathologically nor histopathological. When exposed to interferon alpha nebulization. In the meantime, the vehicle used has proved to be quite safe and also provided a suitable medium to allow interferon alpha to initiate the innate immunological effect.
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