Methylene blue preparation technology for controlling epidemic outbreak through enveloped virus gene targeted therapy

Abstract

The invention relates to a methylene blue preparation technology for controlling epidemic outbreak through enveloped virus gene targeted therapy. The key point is that different epidemic situations caused by enveloped viruses or non-enveloped viruses are summarized and recognized from thousands of viruses and epidemic situations which are emerged all the time. The enveloped virus can be effectively inactivated by adopting light to activate methylene blue. The methylene blue can be embedded into a virus nucleic acid chain through light activation, and virus nucleic acid replication can be prevented, so that inactivation targeted therapy is achieved. The method is a breakthrough for controlling outbreak of epidemic situation in epidemic situation treatment. According to the preliminary result, the No.2 preparation of the light activated methylene blue is orally taken once every two days, and 120 milligrams of the No.2 preparation are taken each time. 15 times of treatment, all three or five positive cases of hepatitis B can be effectively turned to negative, and various preparations No.1 and No.3 have no obvious effect. The preparation process determines the curative effect. An effective way for treating and controlling propagation is explored for controlling threats to human life caused by epidemic situation propagation and outbreak. The preparation process comprises the steps of preparing the photo-activated methylene blue and the capsules, tablets and granules of the photo-activated methylene blue.

Description

Technical Field

[0001] The field of epidemic treatment and prevention for effectively treating enveloped virus infectious diseases, controlling the acute spread of the epidemic, controlling the outbreak of the epidemic, and avoiding threats to human life, health, public health, and social economy. Background Art

[0002] After inquiry, no identical background art was found. Summary of the Invention

[0003] From thousands of viruses and numerous past epidemics, it is recognized that the viruses causing epidemic spread are mainly two categories: enveloped and non-enveloped viruses. Recognizing the characteristic differences between these two categories of viruses, namely being enveloped and non-enveloped, is the breakthrough point for epidemic prevention and treatment.

[0004] The rapid spread of the virus is mainly due to the lack of understanding of the characteristics of the spreading virus, resulting in helplessness. Understanding the characteristics of the spreading virus is the key.

[0005] Utilizing the unique chemical structure of methylene blue, which can be activated by light and has an inactivating effect on numerous enveloped viruses, is the breakthrough point for solving the treatment of epidemic spread.

[0006] All kinds of epidemics that have broken out over the years have brought disasters to humanity. Using light activation to inactivate the envelope is an effective way to treat infectious diseases and control the outbreak of the epidemic.

[0007] By using a light activation device and preparing a preparation after activating methylene blue, a solution to the treatment of epidemic spread has been explored.

[0008] Preliminary results show that the preparation process determines its efficacy.

[0009] Preliminary practical results show that according to the in vivo metabolic process, after taking the methylene blue light-activated preparation, it is excreted from the body in about 46 hours. It is initially determined to take it once every two days, with a dose of 120 mg each time. The dosing dose and drug administration interval have been initially explored.

[0010] Using the methylene blue light-activated preparation to treat cases with positive hepatitis B three or five items, the preliminary observation results show that taking the drug once every two days for 15 times, all cases turn negative effectively. However, there is currently a lack of targeted drug treatment.

[0011] By using a light activation device and using the methylene blue light-activated preparation to treat virus infectious diseases, controlling the spread and outbreak of the epidemic to avoid threats to human life, health, the public health system, and social economy caused by the outbreak of the epidemic. Technical Solution

[0012] From thousands of viruses and from the epidemics that have broken out over the years, it is recognized that they are caused by many enveloped or non-enveloped viruses, which is an effective breakthrough for treating various epidemic infectious diseases and controlling the spread and outbreak of various epidemics.

[0013] For example 1 of the basis of the solution, the outbreak of the epidemic has brought unprecedented challenges to the global public health system and social economy. The acute outbreak of the epidemic has left the world helpless and posed a huge threat to the health of the people. The epidemic is spread by enveloped DNA / RNA coronaviruses. And there are currently no effective control methods and effective treatment drugs.

[0014] For example 2 of the basis of the solution, viral hemorrhagic fever is an acute infectious disease with fever and bleeding as the main clinical symptoms, which seriously threatens human health. During the epidemic, about 390 million people were infected, and more than one-third of the global population lives in high-risk infection areas. The epidemic of viral hemorrhagic fever is spread by enveloped DNA / RNA yellow fever virus, West Nile virus, dengue virus, Crimean-Congo hemorrhagic fever virus, Ebola virus, chikungunya virus, and there are currently no effective control methods and effective treatment drugs.

[0015] For example 3 of the basis of the solution, hepatitis B infection is still a serious public health problem worldwide. There have been 2 billion people infected with the hepatitis B virus worldwide, of which 350 million have become hepatitis B virus patients, and about 1 million people die each year from liver failure, cirrhosis, and liver cancer caused by hepatitis B virus infection. And there are currently no effective control methods and effective treatment drugs.

[0016] For example 4 of the basis of the solution, photoactivated methylene blue has good inactivating effects on enveloped human immunodeficiency virus, hepatitis B virus, hepatitis C virus, West Nile virus, herpes simplex virus, Crimean-Congo hemorrhagic fever virus, Nipah virus, Zika virus, yellow fever virus, Ebola virus, dengue virus, chikungunya virus.

[0017] For example 5 of the basis of the solution, the inactivating mechanism of photoactivated methylene blue on enveloped viruses. Methylene blue can be embedded with the viral nucleic acid chain. Through visible light activation, energy transfer generates highly reactive singlet oxygen, which oxidizes guanosine in the viral nucleic acid chain, thereby destroying the viral nucleic acid chain and preventing the replication of the viral nucleic acid chain to achieve the inactivation of the virus.

[0018] For example 6 of the basis of the solution, as early as the beginning of the 20th century, it was found that the visible light activation of methylene blue can inactivate most lipid-enveloped DNA and RNA viruses. The S+ in the methylene blue molecule phenothiazine-5 can be activated by visible light to be an organic ion catalyst, catalyzing the destruction of enveloped and intracellular organelle membranes to achieve inactivation.

[0019] Based on Example 7, for the inactivation of enveloped viruses, the enveloped lipids are the main components of cell membranes and intracellular organelle membranes. The fluidity of cell membranes is an important characteristic of lipid membranes, and maintaining appropriate fluidity is very important for the normal functions of lipid membranes. The electron transport chain and other reactions in intracellular mitochondria will generate various reactive oxygen species, such as superoxide radicals, hydroxyl radicals, etc. These reactive oxygen species are prone to react with biomolecules, such as lipids, DNA / RNA, and protein molecules, and change their functions. Since the lipid membrane contains unsaturated lipids, it is easily affected by oxidants, resulting in lipid peroxidation. After lipid peroxidation, in addition to causing structural changes, it will also affect the normal fluidity of the lipid membrane, causing cell damage and inactivation.

[0020] The solution uses a photoactivation device. The methylene blue sample is placed on the device backing plate according to the set thickness. According to the set sample thickness, set illuminance, set light activation time, number of light activation times, and the sample is mixed 3 times to activate methylene blue. And the photoactivated methylene blue samples are numbered.

[0021] The solution prepares the activated methylene blue samples into capsules, tablets, and granules respectively according to the sample numbers and set doses. Example

[0022] For the photoactivation device, 6 pieces of 5 - millimeter - thick glass plates are used to form a cuboid glass box. Among them, 4 pieces are 660 millimeters long and 500 millimeters wide. One of them is used as the bottom. The lower ends of the two other pieces on both sides of the bottom are connected and fixed to the bottom. Then, two glass plates with a width of 400 millimeters and a height of 500 millimeters are respectively set at both ends and are respectively connected and fixed to the bottom and the side glass plates. The fluorescent lamp is fixed inside the top - cover glass, and a stainless - steel plate is set on the bottom of the device. The upper plane of the stainless - steel plate is 300 millimeters away from the fluorescent lamp. When in use, the cover is covered to form the photoactivation device.

[0023] To prepare the photoactivated methylene blue No. 1 sample, take 50 grams of methylene blue pharmaceutical raw material powder, spread it on a stainless - steel plate that is 500 millimeters long and 350 millimeters wide, spread it into a 1 - millimeter - thick sample, place it on the backing plate of the photoactivation device, and cover the lid. Turn on the light. Under the condition of the same illuminance, each light activation lasts for 4 minutes, the sample is mixed and flattened twice again, and after 3 times of light activation, the sample is collected and sealed. It is numbered as the photoactivated methylene blue No. 1 sample.

[0024] To prepare the photoactivated methylene blue No. 2 sample, take 50 grams of methylene blue pharmaceutical raw material powder, spread it on a stainless - steel plate that is 500 millimeters long and 350 millimeters wide, with a sample thickness of 1 millimeter, place it on the backing plate of the photoactivation device, and cover the lid. Turn on the light. Under the condition of the same illuminance, each light activation lasts for 7 minutes, the sample is mixed and flattened 2 times again, and after 3 times of light activation, the sample is collected and sealed for storage. It is numbered as the photoactivated methylene blue No. 2 sample.

[0025] Prepare the photoactivated methylene blue No. 3 sample. Take 50 grams of methylene blue pharmaceutical raw material powder and spread it on a stainless steel plate with a length of 500 mm, a width of 350 mm, and a thickness of 1 mm. Place it on the backing plate of the photoactivation device and cover it with the lid. Turn on the light. Under the condition of the same illuminance, activate it by light for 10 minutes each time. Mix and flatten the sample twice more. After photoactivation for 3 times, collect the sample and store it sealed. Label it as the photoactivated methylene blue No. 3 sample.

[0026] Prepare the photoactivated methylene blue No. 4 sample. Take 50 grams of methylene blue pharmaceutical raw material powder and spread it on a stainless steel plate with a length of 500 mm and a width of 350 mm. The thickness of the sample is 2 mm. Place it on the backing plate of the photoactivation device and cover it with the lid. Turn on the light. Under the condition of the same illuminance, activate it by light for 4 minutes each time. Mix and flatten the sample twice more. After photoactivation for 3 times, collect the sample and store it sealed. Label it as the photoactivated methylene blue No. 4 sample.

[0027] Prepare the photoactivated methylene blue No. 5 sample. Take 50 grams of methylene blue pharmaceutical raw material powder and spread it on a stainless steel plate with a length of 500 mm and a width of 350 mm. The thickness of the sample is 2 mm. Place it on the backing plate of the photoactivation device and cover it with the lid. Turn on the light. Under the condition of the same illuminance, activate it by light for 7 minutes each time. Mix and flatten the sample twice more. After photoactivation for 3 times, collect the sample and store it sealed. Label it as the photoactivated methylene blue No. 5 sample.

[0028] Prepare the photoactivated methylene blue No. 6 sample. Take 50 grams of methylene blue pharmaceutical raw material powder and spread it on a stainless steel plate with a length of 500 mm and a width of 350 mm. The thickness of the sample is 2 mm. Place it on the backing plate of the photoactivation device and cover it with the lid. Turn on the light. Under the condition of the same illuminance, activate it by light for 10 minutes each time. Mix the sample twice more. After photoactivation for 3 times, collect the sample and store it sealed. Label it as the photoactivated methylene blue No. 6 sample.

[0029] Prepare the capsule of the photoactivated methylene blue No. 1 sample. Take 12 grams of the photoactivated methylene blue No. 1 sample and add 0.6 grams of pharmaceutical starch. Mix the two, granulate, fill into No. 3 hollow capsules, and package. Label it as the photoactivated methylene blue No. 1 capsule, with a dose of 120 mg per capsule.

[0030] Prepare the tablet of the photoactivated methylene blue No. 1 sample. Take 12 grams of the photoactivated methylene blue No. 1 sample and add 0.6 grams of pharmaceutical starch. Mix the two, granulate, tableting, and package. Label it as the photoactivated methylene blue No. 1 tablet, with a dose of 120 mg per tablet.

[0031] Prepare the granule of the photoactivated methylene blue No. 1 sample. Take 12 grams of the photoactivated methylene blue No. 1 sample and take 0.6 grams of pharmaceutical starch. Mix the two, granulate, and fill into an aluminum-plastic film bag and seal the package. Label it as the photoactivated methylene blue No. 1 granule, with a dose of 120 mg per bag.

[0032] Prepare the capsule of photoactivated methylene blue sample No. 2. Take 12 g of photoactivated methylene blue sample No. 2 and 0.6 g of medicinal starch. Mix the two, granulate, fill into No. 3 empty capsules, and package. Label it as photoactivated methylene blue capsule No. 2, with a dose of 120 mg per capsule.

[0033] Prepare the tablet of photoactivated methylene blue sample No. 2. Take 12 g of photoactivated methylene blue sample No. 2 and 0.6 g of medicinal starch. Mix the two, granulate, press into tablets, and package. Label it as photoactivated methylene blue tablet No. 2, with a dose of 120 mg per tablet.

[0034] Prepare the granule of photoactivated methylene blue sample No. 2. Take 12 g of photoactivated methylene blue sample No. 2 and 0.6 g of medicinal starch. Mix the two, granulate, and subpackage into aluminum-plastic film bags, then seal and package. Label it as photoactivated methylene blue granule No. 2, with a dose of 120 mg per bag.

[0035] Prepare the capsule of photoactivated methylene blue sample No. 3. Take 12 g of photoactivated methylene blue sample No. 3 and 0.6 g of medicinal starch. Mix the two, granulate, fill into No. 3 empty capsules, and package. Label it as photoactivated methylene blue capsule No. 3, with a dose of 120 mg per capsule.

[0036] Prepare the tablet of photoactivated methylene blue sample No. 3. Take 12 g of photoactivated methylene blue sample No. 3 and 0.6 g of medicinal starch. Mix the two, granulate, press into tablets, and package. Label it as photoactivated methylene blue tablet No. 3, with a dose of 120 mg per tablet.

[0037] Prepare the granule of photoactivated methylene blue sample No. 3. Take 12 g of photoactivated methylene blue sample No. 3 and 0.6 g of medicinal starch. Mix the two, granulate, and subpackage into aluminum-plastic film bags, then seal and package. Label it as photoactivated methylene blue granule No. 3, with a dose of 120 mg per bag.

[0038] Prepare the capsule of photoactivated methylene blue sample No. 4. Take 12 g of photoactivated methylene blue sample No. 4 and 0.6 g of medicinal starch. Mix the two, granulate, fill into No. 3 empty capsules, and package. Label it as photoactivated methylene blue capsule No. 4, with a dose of 120 mg per capsule.

[0039] Prepare the tablet of photoactivated methylene blue sample No. 4. Take 12 g of photoactivated methylene blue sample No. 4 and 0.6 g of medicinal starch. Mix the two, granulate, press into tablets, and package. Label it as photoactivated methylene blue tablet No. 4, with a dose of 120 mg per tablet.

[0040] Prepare the granule of photoactivated methylene blue sample No. 4. Take 12 g of photoactivated methylene blue sample No. 4 and 0.6 g of medicinal starch. Mix the two, granulate, and subpackage into aluminum-plastic film bags, then seal and package. Label it as photoactivated methylene blue granule No. 4, with a dose of 120 mg per bag.

[0041] Prepare the capsule of photoactivated methylene blue No. 5 sample. Take 12 grams of photoactivated methylene blue No. 5 sample and 0.6 grams of medicinal starch. Mix the two evenly, granulate, fill into No. 3 hollow capsules, and package. Label it as the capsule of photoactivated methylene blue No. 5, with a dose of 120 mg per capsule.

[0042] Prepare the tablet of photoactivated methylene blue No. 5 sample. Take 12 grams of photoactivated methylene blue No. 5 sample and 0.6 grams of medicinal starch. Mix the two evenly, granulate, press into tablets, and package. Label it as the tablet of photoactivated methylene blue No. 5, with a dose of 120 mg per tablet.

[0043] Prepare the granule of photoactivated methylene blue No. 5 sample. Take 12 grams of photoactivated methylene blue No. 5 sample and 0.6 grams of medicinal starch. Mix the two evenly, granulate, and subpackage into aluminum-plastic film bags, then seal and package. Label it as the granule of photoactivated methylene blue No. 5, with a dose of 120 mg per bag.

[0044] Prepare the capsule of photoactivated methylene blue No. 6 sample. Take 12 grams of photoactivated methylene blue No. 6 sample and 0.6 grams of medicinal starch. Mix the two evenly, granulate, fill into No. 3 hollow capsules, and package. Label it as the capsule of photoactivated methylene blue No. 6, with a dose of 120 mg per capsule.

[0045] Prepare the tablet of photoactivated methylene blue No. 6 sample. Take 12 grams of photoactivated methylene blue No. 6 sample and 0.6 grams of medicinal starch. Mix the two evenly, granulate, press into tablets, and package. Label it as the tablet of photoactivated methylene blue No. 6, with a dose of 120 mg per tablet.

[0046] Prepare the granule of photoactivated methylene blue No. 6 sample. Take 12 grams of photoactivated methylene blue No. 6 sample and 0.6 grams of medicinal starch. Mix the two evenly, granulate, and subpackage into aluminum-plastic film bags, then seal and package. Label it as the granule of photoactivated methylene blue No. 6, with a dose of 120 mg per bag.

[0047] The purpose of preparing each sample into capsules, tablets, and granules is as follows: from the perspective of the absorption rate in the body, granules are absorbed quickly, capsules are absorbed more slowly, and tablets are absorbed the slowest; from the perspective of patient adaptability, coated tablets and granules need to contain sugar, which is not suitable for diabetic patients; in order to observe the results, additives in the preparation should be minimized as much as possible.

[0048] The preparations in this plan are for numerous infectious viruses. For patients with different viruses, there are differences in the irradiation activation time. Especially in the early stage of the epidemic, when the transmitted virus is unknown, a small number of cases can be selected to observe the treatment effects of samples with different light exposure times, so as to quickly determine whether it is the transmission of enveloped viruses or non-enveloped viruses, achieve targeted prevention and control and treatment as soon as possible, and facilitate popularization and application.

[0049] To determine the medication time, based on the initial trial, observe how long it takes to be metabolized and excreted from the body by the change in urine color after taking the medicine. As a result, it can be metabolized and excreted about 46 hours after taking. It can be set to take once every two days, 120 mg each time.

[0050] Due to the existence of positive cases of hepatitis B virus infection, there is currently no effective drug treatment. The preliminary tests on Samples 1 to 6 showed that taking Sample 2 15 times can effectively turn all cases with three positive or five positive hepatitis B items negative. Sample 2 has the best effect. The results show that the preparation technology determines the curative effect.

[0051] For patients already diagnosed with an enveloped virus infectious disease, the photoactivated methylene blue preparation can achieve targeted treatment. For the targeted treatment of non-enveloped virus infections, a patent has been applied for separately.

[0052] The samples of this application are prepared according to the technical solution. The practical results of the various preparations show that the technical solution of this application is basically feasible.

Claims

1. A type of methylene blue preparation technology for gene-targeted therapy of enveloped viruses to control the outbreak. The key is to summarize and realize from thousands of viruses that there are different epidemics caused by enveloped viruses and non-enveloped viruses, and that methylene blue can be activated by visible light and embedded in the viral nucleic acid chain molecules, which can prevent the replication of viral nucleic acid chains and achieve effective treatment and prevention and control. It is a key breakthrough in epidemic prevention and control treatment. It is initially observed that using a light-activated device, according to the set conditions, methylene blue can be light-activated and taken and can be excreted from the body in about 46 hours. Take 120 mg each time, take it once every two days, and take Preparation No. 2 15 times. All cases with three or five positive hepatitis B items can be effectively turned negative, and Preparations No. 1 and No. 3 have no obvious effect. It was observed after taking it that the preparation process determines the efficacy. The preparation process includes a light activation device; light activated methylene blue sample preparation; under set conditions, sample 1 is light activated for 4 minutes each time, the sample is mixed 3 times, the light is activated 3 times, and the sample thickness is 1 mm; sample 2 is light activated for 7 minutes each time, the sample is mixed 3 times, the light is activated 3 times, and the sample thickness is 1 mm; sample 3 is light activated for 10 minutes each time, the sample is mixed 3 times, the light is activated 3 times, and the sample thickness is 1 mm; sample 4 is light activated for 4 minutes each time, the sample is mixed 3 times, the light is activated 3 times, and the sample thickness is 2 mm; sample 5 is light activated for 7 minutes each time, the sample is mixed 3 times, the light is activated 3 times, and the sample thickness is 2 mm; sample 6 is light activated for 10 minutes each time, the sample is mixed 3 times, the light is activated 3 times, and the sample thickness is 2 mm. Each sample is prepared in capsule form, tablet form, and granule form. The methylene blue pharmacopoeia is classified as an antidote.

2. The visible light activated device according to claim 1, characterized in that: Six glass plates are used, four of which are 660 mm long, 500 mm wide and 5 mm thick. One of them is used as the bottom, two of them are used as the wall, and the lower ends of the two side walls are connected and fixed to the bottom along the length. Two of them are 400 mm wide and 500 mm high, respectively set at both ends of the three long glass connectors and fixed, and the remaining 1 glass with a length of 660 mm and a height of 500 mm is used as a cover to form a glass box, a fluorescent lamp is set at the lower end of the box cover, and a pad is set on the inner side of the box bottom, and the height between the pad plane and the lamp is 300 mm, forming a light activation device.

3. The sample 1 according to claim 1, characterized in that: Place the methylene blue sample on the pad of the light activation device, and activate it for 4 minutes each time under the same light intensity. Mix and flatten the sample 3 times, activate it 3 times, and the sample thickness is 1 mm. After the light is over, collect the sample and seal it. It is named methylene blue light activation sample No.

1.

4. The sample 2 according to claim 1, characterized in that: Place the methylene blue sample on the pad of the light activation device, and activate it for 7 minutes each time under the same light intensity. Mix and flatten the sample 3 times, activate it 3 times, and the sample thickness is 1 mm. After the light is over, collect the sample and seal it. It is named methylene blue light activation sample No.

2.

5. The sample 3 according to claim 1, characterized in that: Place the methylene blue sample on the pad of the light activation device, and activate it for 10 minutes each time under the same light intensity. Mix the sample and flatten it 3 times, activate it 3 times, and the sample thickness is 1 mm. After the light is over, collect the sample and seal it. It is named methylene blue light activation sample No.

3.

6. The sample 4 according to claim 1, characterized in that: Place the methylene blue sample on the pad of the light activation device, and activate it for 4 minutes each time under the same light intensity. Mix and flatten the sample 3 times, activate it 3 times, and the sample thickness is 2 mm. After the light is over, collect the sample and seal it. It is named methylene blue light activated sample No.

4.

7. The sample 5 according to claim 1, characterized in that: Place the methylene blue sample on the pad of the light activation device, and activate it for 7 minutes each time under the same light intensity. Mix the sample and flatten it 3 times, activate it 3 times, and the sample thickness is 2 mm. After the light is over, collect the sample and seal it. It is named methylene blue light activation sample No.

5.

8. The sample 6 according to claim 1, characterized in that: Place the methylene blue sample on the pad of the light activation device, and activate it for 10 minutes each time under the same light intensity. Mix the sample and flatten it 3 times, activate it 3 times, and the sample thickness is 2 mm. After the light is over, collect the sample and seal it. It is named methylene blue light activated sample No.

6.

9. The capsule according to claim 1, characterized in that: According to the set dosage, 5% medicinal starch is added to each of Sample 1, Sample 2, Sample 3, Sample 4, Sample 5 and Sample 6, mixed and granulated, and then filled into hollow capsules for packaging. They are respectively numbered as Sample Capsule No. 1, Sample Capsule No. 2, Sample Capsule No. 3, Sample Capsule No. 4, Sample Capsule No. 5 and Sample Capsule No.

6.

10. The tablet according to claim 1, characterized in that: According to the set dosage, 5% medicinal starch was added to each of Sample 1, Sample 2, Sample 3, Sample 4, Sample 5 and Sample 6, mixed and granulated, and then pressed into tablets and packaged. They were numbered as Sample Tablet No. 1, Sample Tablet No. 2, Sample Tablet No. 3, Sample Tablet No. 4, Sample Tablet No. 5 and Sample Tablet No. 6 respectively.

11. The granule according to claim 1, characterized in that: According to the set dosage, 5% of medicinal starch is added to each of Sample 1, Sample 2, Sample 3, Sample 4, Sample 5 and Sample 6, mixed and granulated, and then divided into granule aluminum plastic bags for packaging. They are respectively numbered as Sample 1 Granules, Sample 2 Granules, Sample 3 Granules, Sample 4 Granules, Sample 5 Granules and Sample 6 Granules.

12. In clinical observation and clinical application, according to actual needs, adjust the light activation time, number of activations, sample paving thickness, dosage, and preparation process, improve the structure of the light activation device, or increase the dosage form and indications.