Model of Information Technology in Pharmaceutical Application (MITPA)

Technical field:

Our project aim is to replace the clinical trial studies that actually done on the humans by several systems that make simulation of the human body to perform on it clinical trials. Hence our project aim to develop the clinical research in the pharmaceutical field. Background Art:

There is no background art. Disclosure of invention:

The aim of this project is to decrease the hazards resulting from some clinical trials done on human beings. This could be achieved by performing a model of the various organs of the human body with all the details as possible. Consequently, one can reduce clinical trial of massive costs and medical supervision. So that we can decrease the time taken to launch the new products. This could be accomplished by performing some tests in few hours in stead of few years. This project is based on different techniques dealing with: 1 -Stereochemistry. 2-Physiology. 3 -Histology. 4-Anatomy. 5 -Psychology. 6 -Biochemistry. 7-Pathology. 8 -Parasitology. 9-Pharmacology. 10-Microbiology. 11 -Pharmaceutical chemistry. 12-Drug design. 13 -Molecular biology. 14-Nano-technology. 15 -Pharmacokinetics. 16-Pharmaceutics. 17-Biotechnology. 18 -Spectrochemistry. 19-Genetic map.

All this sciences are collected as a data for building up the software which designed to work by the parallel thinking. This software gives best results

of the analysis of the input data added by the user of this apparatus. Apparatus is divided into three sections. Namely:

1 -Machines. 2-Software. 3-Printer.

1 - Machines: consists of four units which help to reduce the deviation from the ideal outcome of such clinical studies as environmental factors and drug dissociation and dissolution.

2 - Software: The input data must contain the molecular formula of the drug and the type and ratio of the additives then software create the 3D form of each. The drug enter blood then reach the cells, and binds to receptors located on the cell wall, which form exactly the image of the 3D form of the drug active side. The drug may have several active sites so act on several receptors (for simplifying lock and key method). So it gives different effects. Consequently one can predict accurately the actual effect of the drug.

3 - Printer: When binding of the drug on the receptor the drug gives its effect, so this program can investigate the therapeutic and side effects of the drug. Thus, we can do clinical trial on it. So printer's function is to print the results of each organ of the human body.

1 - Devices (machines): • Machine I:

The aim of this unit is to receive the pharmaceutical dosage form and mix it to react with different body fluids.

This could be achieved by making simulation of the human body organ capacity and morphology. Then we have to make this organ to have the same movement as the normal organ movements. So this simulation can exert the same force of pressure and surface area to make the reaction of this pharmaceutical dosage form like that in the human body. Hence we will supply this simulation with the body fluids of each organ of the GIT. From the previously mentioned information we designed this device as follows:

There are tubes that contain the body fluids for each organ of the GIT. These tubes have the capacity of fluids exactly the organ have. Also they are located out the operation area. Its bottoms are funneled shaped to make complete transfer of the fluids to the operation area (the lens). The lens is made of elastic polymer and its role is to take the shape of the human organ. This could be obtained by fuse three dimensionally polymer pieces to the lens that attached to external molds of the outline of the human organ. So we have obtained the shape of the human organ. Then we will put the pharmaceutical dosage form and the organ fluid in the lens.

Then we have to make the lens to perform the organ movement in the required time. So we connect the lens to a timer which control the time of contact between the pharmaceutical dosage form and the organ fluid in the required organ shape. The lens movement designs depend on one of the following:

A- It depends primarily on the effect of the magnetic field on the polymer pieces doped with magnetic substance which lens is made of. The reshaping of the polymer in the form of the human organ shape takes place. Then charge the right side of the lens with positive magnetic field and the left side of it with negative field so the required movement can be obtained. When we stop the surrounding magnetic field the attraction between the negative and positive sides will be disappeared. So with these sequences of attraction and release we can make the required movements of the organs.

B- One can control the shape and the motion of the polymer piece by using a STEEPER MOTOR. This controls the movement of the organs so for example peristalsis movement of the intestine and the movement of stomach during digestion and other movements of GIT human organs. This design is better than Design (A), because in (A) the magnetic field strength diminishes after a period and it is in quite enough to perform the required movements.

Then each drainage of the organ fluid with the soluble pharmaceutical dosage form are collected in the collecting container, we adjust the last drainage of the intestine to the PH 8 which is the PH of the intestine by the usage of PH adapter with the use of NaHcO ₃ which is normally used in the intestine to adjust the PH. We do this to activate the enzymes that present in the intestinal fluid. So it can make changes in the structure of the drug and its additives. Then all fluids collected in it will be transferred to NMR and MASS spectrometers to measure the molecular formula of the drug and the additives. Also we use them to evaluate the concentration of each pharmaceutical dosage form component. They programmed to cancel the body fluids components readings. Then these data transferred to the software to work on it.

For more details see the flash product attached with the papers. • Machine II:

The design depends on the following:

-It is based on Newton secand law of motion in physics, which provides for the following:

"The acceleration of an object as produced by a net force is directly proportional to the magnitude of the net force, in the same direction as the net force, and inversely proportional to the mass of the object." This device aimed to measure the spreading of micro-organisms in the air and their kind. This apparatus can contain Im ³ of the air tightly closed. The

role of Vacuum pump is to suck the air inside the apparatus through the openings of width smaller than the diameter of the micro-organisms. The virtual diameter is IA ⁰ . So we can obtain free fall of the micro-organisms without any air resistance. The suction force is calculated to avoid disruption of micro-organisms. Assuming that the height of the apparatus is equal to Im (The gravity = 9.8 m/s).

The rapid fall of the micro-organisms will be in 1/9.8 second after the time of the suction. Thus, we can collect all micro-organisms in the air. Water can be added to make different titers of the micro-organisms. Thus they could be easily separated. We must separate the micro-organisms from each other by using ultra centrifuge which is sensitive to small differences in weight through centrifugal force at different rates per minute (rpm) values. As example bacteria and viruses could be precipitated respectively at rate equal 400rpm and 7000rpm. Identification of the micro-organisms types is carried out by one of the following methods:

* Dying of the micro-organisms is an optional matter to be done, then the use of the examinational power of the electron microscope. The results of this process are transferred to the secondary software which contains a wide data base of the morphology of each bacteria or viruses and the nucleus of them. There is a camera hanged up the electron microscope that takes a picture for the organisms and its nucleus. From the input of this data, the secondary software compare between the two pictures that integrated already in the data base, so we can determine each of the microorganisms type and their number. Then this data transferred to the main software.

* By the usage of laser beam that automatically directed to the m.o. under the electron microscope:

1-The reflection of the beam can detect the no. and type of it. 2-By calculating the difference in the absorbance of each m.o. to the laser beam by the use spectrophotometer.

As Raman scattering method used in blood counting devices. There is anther model that make the same role of this device. As it can collect the bacteria from the air as follows:

The bacterial collectable rolling ball:

This devise is a box of isolated diamagnetic dielectric material, inside it composed of a set and poles by side the internal surface of the box. It works alternatively. The main purpose of those poles is to force a metal magnetized out side ball to rotate.

This ball is symmetric ball. The internal crust of the ball is small tubes ends with holes which locate on the internal surface of the ball. Main gel source is responsible to distribute the gel like (gelatin) to these small tubes.

The device is working as the following:

After the set is moving up mechanically to collect air. It attends to close.

Then the box will be closed. The poles will work automatically so that the ball will separate from the set. Then the set will move downward to the base.

The ball will begin to roll and the Bactria inside the ball will concentrate at the center of the ball according to the centrifugal force. Then after a certain time the gel will be sprayed on.

Then the Bactria will be coated like capsules by a coat of the gel material.

We recommend the use of gelatin as it can easily dissolved in the water. So we can make different titers of micro-organisms. We can get the purified air from this apparatus by the following method:

An attached tube will appear after the ball stop to roll. It will absorb the remained air. Then transfer it to NMR and MASS spectrometer to measure air components percentage after collecting the bacteria. Then complete the procedure as mentioned above.

Therefore one can accurately investigate one of the Environmental factors affecting on human being.

The purified air will be analyzed by using NMR and MASS spectrometers to give information about the ratios and types of gases in the air. The air could affect strongly on the different biological processes in the human body, e.g.:

A-The presence of Co ₂ in the air increases the temperature of the surrounding environment around patient which affect the metabolic process and also on drug metabolism in the trial. Co ₂ cause tissue hypoxia which affects also on the metabolic process and drug metabolism.

B-The presence of co in x% which has 220 times affinity higher than O ₂ to

Hb indicates how much methemo Hb formed, consequently make tissue hypoxia

For more details see the flash product and movies attached with the papers.

• Machine III:

The goal is to make complete blood, urine and stool tests for the trial in only one device; hence one can detect infection with some types of microorganisms and diseases that do not appear on the patient. Consequently clinical studies will be at the highest degree of accuracy. The design depends on the following:

1 - Metal base that move upwards and downwards and fixed under it four groups of capillary tubes that designed with different width and materials that have selective absorption for each component of blood (plasma, platelets, WBCs and RBCs). So that one group of these capillary tubes has the selectivity to plasma, other to RBCs, other to WBCs and other to

platelets. So it can easily separate all blood components from each other. Blood sample will be 5ml. Assuming that the volume of plasma=2ml, volume RBCs = ImI, volume of WBCs = ImI and volume of Platelets = ImI. Hence the volume of the plasma can be absorbed by 20 capillary tubes if the capacity of one of them is 0.1ml. This calculation is repeated with other blood components. We absorb plasma first, then the platelets, then the WBCs, then lastly the RBCs. So the concept of absorption is to absorb from small particle size to the higher particle size. Mechanism of separation the four blood components: The first tube in unit 3 containing the blood sample.The first group of capillary tubes has specific affinity to the plasma. This group immersed in the first tube of unit 3. So this group absorbs the plasma. Then unit 3 rotates (clockwise) with an angle of 90° to settle the first group over the second test tube and second group over the first test tube. So the first group contains the plasma. Then immerse the second group in the first tube in unit 3 which have specific affinity to the platelets. So platelets are absorbed. Thus the second group contains the platelets. Then unit 3 rotates (clockwise) with an angle of 90° to settle the first group over the third tube and third group over the first tube. That has specific affinity for WBCs. So the third group contains WBCs.

The remainder of the blood sample is the RBCs only. So it will be absorbed by fourth group of the capillary tubes. Then unit 1 is moved to be above unit 5. Then it discharges its contents in four test tubes in sample plate each test tube for one blood components that used for making the tests immediately. Dilution of the sample is an optional matter. We block the capillary tubes from above directly after absorption process to avoid escaping of the blood components after absorption. 2- There is belt that have pores to fix on it blood sample tube. Its role is to make samples reach the area where it will be connected to unit 3.

3 -Under unit 1 there is a unit that consists of base of metal containing four openings where we put test tubes. It has the function to rotate around its axis. So it allows the capillary tubes group to absorb blood components. Also we can integrate in it motor to make it act as a centrifuge if needed.

4-There is a reservoir of the reagents that organized to pump the chemical reagents automatically needed by every reaction. Hence we can carry out each test easily.

5 -The sample plat consists often test groups. So the machine can carry out 10 full blood samples at the same time. It is connected to steeper motor that move it in spiral movement as make it move to left to T2 then downwards to T3 then to right to T4 and so on.

6-There is a unit under the sample plat which used to transfer the four components of the blood to the four cuvates of unit7 to carry out blood tests. Its function also is to transfer blood components to the electron microscope to make the blood counting for each component of the blood and the bacteria that present in the blood. This can be obtained by the two mechanisms that mentioned in machine II which are hanging a camera on the electron microscope or Raman Scattering method.

7- It is located under unit 6. It depends on the fact that almost tests of the blood and urine ends with giving a color. This color measured by the colorimeter. The concept of the colorimeter as simple explanation (There is a source that sending light in front of the cuvette and source that accept light behind the cuvette which measures the amount of light absorbed by the color existing in the sample after testing them). Cuvettes are distributed as cubic shape under unit 6 four needles. Within this cubic shape there are the light receptors. They are placed behind the cuvettes. There are outside the cubic shape the light sources that we put in front of cuvettes. These light sources are controlled automatically on the wave length and light intensity required. The cuvette considered as the test operation area where the sample and the reagents added. We are using kinetic reaction for performing blood tests as it isn't take a lot of time. So we can obtain accurate and fast results.

8 -There is urine sample container that transfers the urine sample to the electron microscope. It is transferred by making drops of the sample on consequent slides that moved to the electron microscope by belt. Under this belt there is a flam which makes the slides to be dried after exposure to it. So we can make examination of it by the microscope by the two mechanisms mentioned above. We also make the urine test by making direct discharge of urine sample to the cuvettes in unit 7. So chemical reagents can be added easily and get test results by the usage of kinetic reaction also.

9-There is stool sample container which has a side knife that fixed from one side and rotates in circular motion. Its role is to make spread of the stool sample on the microscope slide. So it can be examined easily under the electron microscope. One can identify micro-organisms in it by the two mechanisms mentioned above. 10-We use in this device the electron microscope which has the golden role in machine II and III as it takes the whole micro-organisms yield from them. Then identifying and counting the micro-organisms take place.

Then this data enter the computer. So the computer will use this data in the required purposes. For more details see the flash product attached with the papers.

• Machine IV:

It is a photocell that can measure the components of light located at the place where the trial is done. This could accomplished by identifying the type of light (UV, IR, X-ray and so on) by determining the average frequency of this radiation. Also we determine the intensity of every radiation. Then this input data will be transferred to the software to measure effect of these environmental factors on the clinical trial.

As light radiations affect on the drug properties in the human body. Also these radiations have an effect to the organs of the human body. Hence affect the effect of the drug on the human body. 2 - Program (main software):

It is based on several systems that depend mainly on the sciences mentioned previously. These sciences will be modified by unique way serve the goal of this project. The aim of the main software is to simulate the human body to make clinical trials in exchange for doing it on the human being. This could be achieved by introducing the molecular formula of the drug and additives that we get from machine I. Then directly expect the 3D form of the drug and additives. So one can expect the effect of them by search in all the body 3D form of receptors that have the corresponding sequence of them.

So when the search gets its results. The software finds the organ which it present in. Then the software will perform the actions that done when the drug binds to the receptor. So immediately the software can expect the effect of the new drugs. The software will use existing chemical properties of the drug structure to expect the period of drug action. By evaluating the strength (length) of the chemical bond formed between the drug and the receptor. Also the data about some environmental factors measured by machines II and IV will be integrated in the software process. We can also measure the temperature and humidity of the atmosphere. Hence one can reduce the number of the clinical trials done on the humans. Also we can therefore make very accurate studies than those occur now on new drugs. So we can avoid side effects that show after product launching in the pharmaceutical market. We will do the clinical trials by excellent ways that simulate the actual clinical trials. This could be obtained by taking blood, urine and stool samples from the patient who would perform the clinical trial and analyze it by machine III. So we can determine the diseases that he suffering from even if he don't know about it.

Then we will take his finger print or biopsy. So we can get information about his genetics. So we can enter his genetics on the software. Then will make study id for each patient. Hence the software seamed to perform the clinical trial on this patient. After performing the trial the patient will reported by the expected result of the drug on him.

This is some details about the software mechanism:

The results of the program begins from the first place in which the drug have been administered as an example; if the patient take a tablet, so the first place in contact with the drug is the mouth. If this tablet is surrounded by a coat of starch, so decomposition of a part of its coat occur in the mouth to disaccharides. Thus the printer has to print a full report from the mouth of the changes that have occurred to the drug and additives and the mouth. We will carry out the previously mentioned process for all organs that the drug and additives passes by it.

The trial done on this software will be at higher probabilities than the trial done on the humans as we can choose different diseases and illnesses to see drug disease interactions at wide range of variables.

The variables are introduced to the software. These variables documented for each person who performs such tests. Such as:

1 - Length, waist and weight and determinations. When introducing it to the software, it will calculate hypothetically the muscle mass and every organ surface area which from its value one can put hypothetical number of the cells in each organ of the body. Thus for example we can determine the percentage of inflammation in every organ because the sensitivity to the drug and additives (allergic reactions).

2 - Introducing the difference in sex, race and other variables that affect the impact of the drug medication.

3 - Adapt the conditions of pregnancy and lactation when the trail on females and other conditions which represent great importance in clinical trials. So we can therefore forbid the use of this drug during pregnancy as it may cause complications to the fetus.

4 - Adapt the software to work on the prevented medical studies such as the gene therapy.

5 - Use it in the new researches that have been discovered recently, such as nanotechnology and molecular Biology.

To get all this, we use a method called parallel thinking. We can obtain this by giving the software the specific scientific facts about the human body. The software will search into existing organ's receptors corresponding to the drug molecule. Through the chemical nature of the drug we could account for the effect of modern and old drugs. Also the machines have a great role in giving us the factors that essential to decrease the deviation in these experiments. For more details see the flash product attached with the papers.

3 - Printer:

When the drug active site binds to the corresponding receptor. The software can know the therapeutic effects and side effects of the drug. The role of the printer is to print report of the results of each organ of the human body.

Brief Description of Drawings:

Figure (M-I): - This are tubes that contain the normal body fluids which react with the pharmaceutical dosage form. It designed to have the capacity of each organ fluids accurately. It is connected to reservoir that refills it after each usage.- This are connecting tubes locating under (1) to transmit all the body fluid in (1) to the lens(3) by the effect of the gravity. - This is the lens which is the place where the body fluids and the pharmaceutical dosage form are reacted in. This lens is reshaped to take the morphology and surface area of the human organs. This lens is made of polymer that connected three dimensionally with polymer pieces of higher density that responsible for giving the lens its shape by the usage of outer molds of the organ image. - This is the collecting container that collects drainages after the reaction of the body fluids with the pharmaceutical dosage form. These drainages is adapted to the final PH of the intestine by the use of PH adapter that consume NaHcO ₃ as the adapter of the PH till reach approximately 8 which- is intestine PH to activate the enzymes that present in the body fluids that consequently affect the drug structure. - The whole drainage in (4) is transmitted to this unit which is consist of NMR and Mass spectrometers which give us the concentration and the molecular formula of the drug and additives. These two units can be exchanged by Energy dispersive x-ray apparatus which can also perform their work and with low costs. These results transmitted to the software to work on it.

Figure (M-2):

The figure explains the openings in the device that the vacuum pump connected to it. The container that collect different micro-organisms in water solution. Also it describes the role of the flame for drying the slides to examine it under the electron microscope. Figure (M-3): - Metal base that move upwards and downwards and fixed under it four groups of capillary tubes that designed with different width and materials that have selective absorption for each component of the blood. So that one group of these capillary tubes has the selectivity to plasma, others to RBCs, others to WBCs and others to platelets. So it can easily separate all blood components from each other. - There is belt that have pores to fix on it blood sample tube. Its role is to make samples reach the area where it will be connected to unit 3. - It consists of base of metal containing four openings where we put test tubes. It has the function to rotate around its axis. So it allows the capillary tubes group to absorb blood components. Also we can integrate in it motor to make it act as a centrifuge if needed.

- It is the reservoir of the reagent that organized to pump the reagent automatically needed by every reaction. Hence we can carry out each test easily. - It is called sample plat it consist often test groups. So the machine can carry out 10 full blood samples at the same time. It is connected to steeper motor that move it in spiral movement as make it move to left to T2 then downwards to T3 then to right to T4 and so on. - This is device that used to transfer the four components of the blood to the four cuvettes of unit7 to carry out blood tests. Its function also is to transfer it to the electron microscope to make the blood counting for each component of the blood and the bacteria that present in the blood. This can be obtained by the two mechanisms that mentioned in machine two which are hanging a camera on the electron microscope or Raman Scattering method. - It is located under unit 6. It depends on the fact that almost tests of the blood and urine ends with giving a color. This color measured by the colorimeter.

Cuvettes are distributed as cubic shape under unit 6. Within this cubic shape there are the light receptors. They are placed behind the cuvettes. There are outside the cubic shape the light sources that we put in front of cuvettes. These light sources are controlled automatically on the wave length and light intensity required. The cuvette considered as the test operation area where the sample and the reagents added. We are using kinetic reaction for performing blood tests as it isn't take a lot of time. So we can obtain accurate and fast results. - Urine sample container that transfer the urine sample to the electron microscope. It is transferred by making drops of the sample on consequent slides that moved to the electron microscope by belt. Under this belt there is a flam which makes the slides to be dried after exposure to it. So we can make examination of it by the microscope by the two mechanisms mentioned above. We also make the urine test by making direct discharge of urine sample to the cuvettes in unit 7. So chemical reagents can be added easily and get test results by the usage of kinetic reaction also. - Stool sample container which have a side knife that fixed from one side and rotate in circular motion. Its role is to make spread of the stool sample on the microscope slide. So it can be examined easily under the electron microscope. One can identify micro-organisms in it by the two mechanisms mentioned above. 0- The electron microscope which has the golden role in machine II and III as it takes the whole micro-organisms yield from them. Then identifying and counting the micro-organisms take place. Then this data enter the computer. So the computer will use this data in the required purposes.

Figure (M-4):

It describes the connections between the main software, the four machines and the printer. Figure (M-5):

The following example is only to simplify and clarify the idea, but it isn't the real performed steps:

This draw represents for the hard disk of the computer. The shaded area formed of four units which called clusters. The clusters are the building unit of the hard disk. The shaded figure is seamed to be like the kidney morphology. Imagine that the scientific information available about the kidney will be developed in this area only. We will put in the upper shaded part the Information of the nephrons which is the building unit of the kidney. Information's about the nephrons contains information about the tissue and cell of it. Thus, the shaded area represents the whole layout of the kidney. Now we can repeat the same imagination with all existing organs in the human body.