TW201219048A - A novel standardized composition, method of manufacture and use in the resolution of RNA virus infection - Google Patents

Abstract

The present disclosure is in relation to antiviral preparations obtained from plant sources namely Cinnamon, Litchi and Arachis. It provides a composition and a process to prepare the composition comprising pentameric procyanidin flavonoid, trimers and tetramers. The composition improves immunity response and found to be useful in treatment and management of HIV infection and AIDS and for the prevention, treatment and management of Influenza virus and infection.

Description

201219048 VI. Description of the Invention: [Technical Field to Which the Invention Is Ascribed] The present invention relates to an antiviral preparation. The present invention provides an antiviral preparation obtained from plants to improve its immune response and is found to be effective against HIV infection, AIDS and influenza viruses and infections. Background Catechin is a polyphenolic plant metabolite belonging to the flavonoid family. The molecular formula and molecular weight of catechins are 290 g/mol. The catechins and epicatechins are epimers, which make (-)-epicatechin and (+)-catechin the most common optical isomers found in nature. Proanthocyanidins or condensed tannins are flavonoid oligomers, and the building blocks are (+)-catechin and (_)-epicatechin. It is the oligomeric end product of the xanthone-based biosynthetic pathway and has now been identified and recognized for its beneficial effects on humans. It is abundantly present in the plant kingdom in fruits, bark, leaves and seeds and is protected against light, oxidation and predators. Proanthocyanidins are found in many plants, mainly apple, pine bark, cinnamon bark, branch peel, peanut, grape seed, cocoa grape skin, mulberry, cranberry, black currant, green tea and black tea. & Proanthocyanidins are classified as Α-type, based on linkages between continuous monomer units, B-type or C-type polyphenols. Through the $' pre-anthocyanin's continuous Liqiu „ _ m 迷 早 早 早 早 早 早 早 Between 第 第 位于 『 口 口 口 口 口 口 口 口 口 , , , , , , , , , , , , , , , , Produce the moon. Or, the bond can exist in the right-handed Shao 』 兀 兀 c4 and 201219048

A c-type proanthocyanidin is produced between C6 and the early c6. Type B and. Type A large number of plant sources are visible. Type A proanthocyanidins are formed when the continuous monomer unit is connected by a "synchronous C2 and C4 of the upper unit and a C7 position of the lower unit and an 8-bit (respectively) oxygen). Compared with type B and polyphenols, 'type A proanthocyanidins are extremely rare. C. Immune Response to Antigens The immune system is a collection of mechanisms by which the host protects against disease by identifying and eliminating pathogens. The system's response to pathogens is identified by the origin of the protein, which ultimately destroys the source of the protein, thereby preserving the dual host. Even the identification of simple proteins from unicellular organisms involves complex steps that result in the ultimate elimination of organisms from the host. This entire process is an immune response to the presence of foreign proteins or antigens.纟Immunal system washes The infection is an immune response to the antigen, and it can be divided into three stages. · Activation and movement: White blood cells (WBC) are activated when foreign molecules or antigens are recognized. The release of immune cells (e.g., macrophages and T cells) attracts: the immune cells attract substances to the location of the identified foreign molecules and thus move countless immune cells to destroy the pathogen. Regulation • The immune response elicited must be controlled to avoid excessive damage to the host. Regulatory + T lymphocytes assist in controlling the immune response by secreting cellular hormones that act as messengers of the immune system, thereby modulating excessive immune responses. One solution: infection resolution involves binding pathogens and eliminating them from the body. After pathogen elimination, most of the WBC is destroyed, and the rest is called “memory cells” and protects the host against future infections caused by the same pathogen by triggering an early immune response to the pathogen. 201219048 Pathogens successfully cause infection when the host is unable to provide protection that is strong enough to eliminate pathogens. In such cases, the antibody produced by the host is not sufficient to neutralize the existing number of antigens. Therefore, the free antigen successfully infects the host. In such cases, use, such as antibiotics and antiviral agents, to aid in reducing the number of antigens. Once the number of antigens is reduced, the immune response is sufficient to eliminate the pathogen. HIV infection and AIDS: Human immunodeficiency virus (HIV) is a retrovirus that destroys the immune system. This infection can eventually lead to acquired immunodeficiency syndrome (aids), a serious and life-threatening condition that prevents the immune system from functioning properly. HIV primarily infects specific cells in the human immune system: r-assisted "lymphocytes (specifically CD4+ sputum cells), macrophages, and dendritic cells. When the number of CD4+ τ cells falls below a critical level, cell-mediated immunity is lost and the body becomes increasingly sensitive to opportunistic infections. HIV life cycle: Once HIV enters the host, HIV needs specific host cells to aid in its replication and reproduction. The host cell in the case of HIV is a tau cell or a CD4 cell. 1. Identification and binding of the host: HIV searches for CD4 cells and attaches to CD4 cells via a co-receptor on the cell surface by a "lock and key" system. Proteins on the surface of HIV attach to complementary proteins on CD4 cells. 2. Attachment and entry into the host: After attachment, HIV injects the viral protein into the cell fluid (cytoplasm) of the tau cells. This allows the cell membrane to fuse with the outer membrane of ΗΙν. 201219048, 3. Decomposition of viral proteins: In order to use its genetic material (r replication, it must dissolve the protective coating surrounding RNA.) M>] RNA Μ. ^ Λ ΠΜδ , right without this step, ..., 忒锊化For DNA (new Ηίν system stop. No,,,. constitutive early 兀), and complex 4 · reverse transcription: once in the cell. Turn into a double-strand dNA. This step must be transferred by the yeast's early strand RNA. This step is caused by the enzyme reverse transcriptase. Use the structural unit from the sputum cell to make the λ person - to help turn the virus into a ship. DNA contains the genetic information needed for HIV replication. 5. Copy and assemble into new virions: for copying

DNA must be integrated into the host cell into a disease I I pole 1f. This process has not yet been fully understood. This process is believed to be a viral transporter protein. In the days of the virus, the virus gradually develops, while the primary cells prepare the proteins they need to replicate. If available, it will be lysed by the virus based on 雹 < t丞 in the coat and structure and then in the group HIV. This process is aided by protease enzymes. V horse is newly germinated from the host cell. The final step of the viral replication cycle is called budding (bUd (4)). As the collection of genetic material and new cells formed by the cell membrane of the host (10) cells are newly formed; HIV is disconnected and enters the ring' ready to start the entire process again. Current interventions: Current interruption methods for replication and reproduction include: viral entry agents; membrane fusion inhibitors; and reverse transcriptase inhibitors; integrase inhibitors; protease inhibitors; Yin Ba has approved many drugs for the infection. Most of these drugs work by their anti-reverse transcription = (ARV) mechanism of action. , 201219048 The infection of human immunodeficiency virus (HIV) raises political, economic, public health, social and scientific challenges for countries around the world. In 2007, it is estimated that there are 33.2 million people living with HIV/AIDS in the world. Therefore, it is necessary to manage and/or treat the disease with safer and more effective drugs. Another challenge raised by this disease is its sensitivity to mutations. The viral protein of HIV* is susceptible to mutations and thus drug-resistant strains form additional months and thus require new classes of drugs. Influenza virus: Influenza is an infectious disease caused by the RNA virus (influenza virus) of the Orthomyxoviridae (〇rth〇tnyx〇viridae), which affects birds and mammals. The infection caused by this virus mainly affects the structure of the nose, throat, bronchial tubes and occasionally affecting the lung β-streaming influenza virus: influenza viruses are classified into three categories: influenza virus Α, Β and c. The three subtypes of the influenza virus have a very similar overall structure. The virus consists of a viral envelope containing two major types of glycoproteins that wrap around the central nucleus. The medium-nucleus contains the viral RNA genome and other viral proteins that package and protect this RNA. Hemagglutinin (HA) and neuraminidase (NA) are two large glycoproteins outside the virion. Streamer flu virus A: Type A virus is the most toxic human pathogen of the three influenza types and causes the most serious diseases. Type A influenza viruses can be subdivided into different serotypes based on antibody responses to these viruses. The serotypes that have been confirmed in humans are (sorted by the number of known human mass deaths): H1Nb H2N2, H3N2, H5Nb H7N7, H1N2, 8 201219048 H9N2, H7N2, H7N3, H10N7. The influenza A virus has caused several epidemics in the last century and continues to cause annual epidemics. The emergence of new strains of epidemic i continues to challenge public health and scientific communities. The H1N1 virus is a serotype of influenza A virus and is one of the known strains of the human being. The H1N1 blood_clear type caused millions of deaths (Spanish Flu) in 1918 and has recently caused a global pandemic of swine flu. ~ L line of influenza virus life cycle: influenza virus replication and reproduction process is summarized as follows: 1. Host identification and binding: the combination of virus and host cells using ΗA protein and sialic acid bound to the surface of epithelial cells Combine. Epithelial cells are typically found in the nose, throat and lungs of mammals and in the intestines of birds. , 2. Attachment and entry into the host: After binding, the ha protein cleaves and the virus enters the cell by pinocytosis. 3. Decomposition of viral proteins: Once the virus enters the cell, the pH and environmental conditions of the endosome cause a. - part of the HA fuses the viral envelope with the tonoplast, b. M2 ion channels allow protons to enter the viral core, protons Acidizing the viral core causes viral core breakdown and subsequent release of viral RN A and core proteins into the host cytoplasm. 4. Reverse transcription: Viral RN A and core proteins are now transported into the nucleus where RNA is transcribed and further translated into viral proteins. 5. Budding from host cells: HA and NA proteins form a cluster around 201219048. The virus RNA and core proteins are then covered, followed by "germination" and propagation of the virus for subsequent infection. As can be seen from the infection and propagation steps detailed above, HA and na play an important role in infection. Να also cleaves sialic acid to prevent sputum from binding to sialic acid prior to release of virions. Current involvement in influenza A virus: There are two types of drugs approved by the US FD A for influenza A virus: ion channel inhibitors such as adamantane (amantadine hydrochloride and rimantadine); Neuraminidase inhibitors such as ossevimivir (TAMIFLU) and Zanamivir (RELENZA). Type A influenza virus is prone to mutation. These mutations are primarily viral proteins such as purine, HA and M2 ion channel proteins, and therefore inhibitors of such proteins will be ineffective against mutant strains. The possibility of mutation and the global pandemic of influenza A in the year of 2009 indicates the urgent need to provide treatments for the treatment and prevention options of this virus. [Prior Art]

Richard Anderson et al., of polyphenols Type A polymer from cinnamon with (6) "//«-//k, in J〇urnal 〇f AgHcu|turai and Food Chemistry, 2004, p. 52, pp. 65_70 e This article describes the product An aqueous extract of cinnamon and having identified a polyphenolic polymer that increases glucose metabolism in the in vitro cell line by about 20-fold. It is prepared using oyster (C7_m pre- (10) heart; K〇rintjicassia) Extract. This variant has a high content of coumarin and cinnamaldehyde. 10 201219048 This document further describes a preparative HPLC method for the preparation and characterization of this aqueous extract. This publication describes the type A double bond of catechins. Pre-anthocyanin is linked. This document has identified a catechin trimer (molecular weight 864), a tetramer (molecular weight 1 52) and an oligomer isolated from cinnamon.

Kilkuskie, <(HIV and reverse transcriptase inhibition by tannins), in Bioorganic and Medicinal Chemistry Letters, 1992, Vol. 2, pp. 1529-1534. This publication evaluates the anti-HIV activity of tannins and condensed tannins and Its ability to inhibit reverse transcriptase enzymes. Although this study found some tannins with anti-Hiv activity, it also has related toxicity. This publication discusses three compounds, which are condensed forms of catechins. 44 and 45 are dimers, trimers and tetramers of catechins. This document considers that there is no correlation between the inhibition of RT enzymes and the anti-HIV effects of these tannins. In addition, molecules 44 and 45 respectively Shows 90% and 73% of anti-HIV activity, but does not exhibit significant RT enzyme inhibition.

Michael Ovadia et al., Patent Application US 2006 275515A1 This patent entitled "Anti-viral preparations 〇btained jy〇ma (10)hra/ (10) describes a natural aqueous extract obtained from cinnamon having antiviral properties. This document describes cinnamon An aqueous extract which is subjected to salting out precipitation with a salt. The precipitate is redissolved in water or buffer and purified using lydose gel chromatography followed by another buffer and galactose. The commonly used salting out process refers to the selection of high molecular weight molecules (usually peptides) 11 201219048. Therefore, it is apparent from this process that the process described in this document aims to recover high molecular weight molecules (about 10 Kda). The active ingredient of the claimed composition has a molecular weight greater than (〇KDA and its response to absorbance at 28 〇 nm is between about 5 and μ 〇 D. The final use of phosphate buffer and galactose from sephar〇n Guangui elutes this compound. Therefore, the final compound will have a high concentration of phosphate and galactose. | Has been in influenza A PR 8 virus, parainfluenza ( The high-molecular-weight compound described in this application was tested in the virus (Sendai), pre-absorption into red blood cells and weight gain in mice infected with influenza or Sendai virus, and in HIV syncytology studies. Example 1 3 describes the test with this extract in MT2 cells to examine the effect on syncytium formation. According to Figure 15 of this application, at 60 to 1 microgram concentration, it inhibits the syncytium. Body formation. Syncytium formation is not a confirmation test for antiviral activity. This is clearly stated in the following publication [Gueseppe pantaleo et al., Eur J immun〇l〇gy 1991, 21, 1771:1774 cdissociation between syncytia formation and HIV spreading Suppressing Syncytia formation does not have refiect inhibition of HIV infection,]. Although the disclosed extracts exhibit the ability to inhibit syncytium formation, it should be noted that only some HIV strains cause syncytia formation. In addition, syncytia formation It is not possible to establish a correlation with the presence or progression of HIV infection or AIDS. Synaptic formation is only a manifestation of performance by some strains. The lack of syncytia formation is incapable of establishing a correlation with the absence of HIV or management of infection. 12 201219048 SUMMARY OF THE INVENTION Objects of the Invention A first object of the present invention is to provide a pentameric proanthocyanidin comprising plant-derived sources. a composition of flavonoids, terpolymers and tetramers. A second object of the present invention is to provide the preparation of pentameric proanthocyanidin flavonoids, terpolymers and tetramers from plant sources such as Cinnamon (Cz. «« (10), Litchi and Peanut). The method of composition. A third object of the present invention is to provide a composition which improves the immune response in an individual and is also effective against HIV infection, AIDS and influenza virus and infection. STATEMENT OF THE INVENTION Accordingly, the present invention is directed to a composition comprising pentameric proanthocyanidin flavonoids in a concentration range of from about 55% w/w to about 99% w/w, each at about 5%. Terpolymers and tetramers ranging from w/w to about 35% w/w concentration, and optionally medically acceptable excipients; preparations comprising a concentration range of from about 55% to about 99% w/w The pentameric proanthocyanidin flavonoids are each about 0.5% w/w to about 35. /. Method for composition of terpolymer and tetramer in a concentration range of w/w' The method comprises the steps of: extracting a pulverized plant body using an organic solvent to remove toxic substances; drying the plant body to remove the organic solvent; Re-extracting the dried plant body with an aqueous solvent to obtain an extract; and purifying the extract through a chromatography column' followed by wave-shrinking, purification, normalization, and an effective amount of the composition of the immune response in the individual Obtaining a composition; improving a need-to-use method comprising administering to a subject a medicine 13 201219048 "The composition contains five small amounts of phthalocyanine in a concentration range of about 55% w/w to about 99% w/w. Flavonoids, trimers and tetramers each ranging from about 0.5% w/w to about 35% w/w, and optionally medically acceptable excipients; and treatment, prevention, and management A method of retroviral infection in a subject in need thereof, the method comprising the step of administering to the individual a medically effective amount of a composition comprising from about 55% w/w to about 99% w/w concentration Polyanthocyanidin flavonoids, each about 5% Terpolymers and tetramers ranging from w/w to about 3 5 °/〇 w/w, and optionally medically acceptable excipients.

Formulations rL The present invention relates to pentameric anthocyanin flavonoids in the range of from about 55% w/w to about 99% w/w, each about O". /. Compositions of terpolymers and tetramers ranging from w/w to about 35% w/w concentration, and optionally medically acceptable excipients. In one embodiment of the invention, the composition is obtained from a plant source selected from the group consisting of Cinnamon, Litchi, and Peanut. In another embodiment of the invention, the preferred concentration of the pentameric proanthocyanidin flavonoid is in the range of from about 80% w/w to about 99% w/w, and the terpolymer and the tetramer are each about 0. 5% w/w to about 20°/. Within the w/w concentration range. In another embodiment of the invention, the pentameric proanthocyanidin flavonoid has a molecular weight of about 1440. In another embodiment of the invention, the pentamer is a type A proanthocyanidin pentapolymer. 14 201219048 In another embodiment of the invention, the excipients are selected from the group consisting of gums, granulating agents, binders, lubricants, disintegrants, sweeteners, colorants, flavoring agents, coating agents A group of plasticizers, preservatives, suspending agents, emulsifiers, antistatic agents, and spheronization agents. In another embodiment of the invention, the composition is formulated to be selected from the group consisting of a tablet, a sugar-coated tablet, a buccal tablet, an aqueous or oily suspension, a dispersible powder or granule, a hard gel capsule or a soft gel. Various dosage forms of the group of emulsions, syrups, and ugly agents in capsules. The present invention relates to the preparation of pentameric proanthocyanidin flavonoids ranging from about 55% w/w to about 99% w/w, each in the range of from about 0.5% w/w to about 35% w/w. Method of composition of terpolymer and tetramer The method comprises the steps of: extracting a pulverized plant body using an organic solvent to remove toxic substances; I drying the plant body to remove the organic solvent; and extracting using an aqueous solvent The dried plant body is subjected to an extract; and the extract is purified via a chromatography column' followed by concentration, purification, standardization, and drying to obtain a composition. In a particular embodiment of the invention, the pulverized plant system is selected from the group consisting of plants of the genus Cinnamon, the genus and the genus Peanut. In another embodiment of the invention, the group of acid ethyl esters and butyl acetate combinations. In the amyl acetate, the organic solvent is selected from the group consisting of ethyl acetate, 2-ethylhexyl acetate and any of the following, including about 8 hours, including coumarin, in another specific example of the invention, the time within the range of the extraction, Preferably, it is about 1 〇 in another embodiment of the invention, the toxicity and the combination. 15 201219048 Passing through a two-stage chromatography column In another embodiment of the invention, the extract is filtered. In another specific embodiment, the 哕恳>~, νβ chromatography column is selected from the group consisting of XAD-7HP and XAD_114 oxime resins. In a further embodiment of the invention, the use of an aqueous solvent is carried out at a pH in the range of from about 3.8 to about 5.8, preferably at about pH. In another embodiment of the invention, the re-extraction is carried out at a temperature in the range of about 90 ° C, preferably 3 rc to 4 (in the range between rc, for a period of from about 8 hours to about 12 hours, Preferably, it is about 1 hour. In another embodiment of the invention, the aqueous solvent is acidified deionized water. In another embodiment of the invention, the composition further comprises an excipient Excipients are selected from the group consisting of gum granules, binder lubricants, disintegrants, sweeteners, colorants, flavoring agents, coating agents, plasticizers, preservatives, suspending agents, emulsifiers, anti-drugs. The present invention relates to a method for improving an immune response in an individual in need thereof, the method comprising the step of administering to the individual a medically effective amount of the composition comprising about 55% w/w Pentameric proanthocyanidin flavonoids in a concentration range of about 99% w/w, trimers and tetramers each ranging from about 0.5% w/w to about 35% w/w, and A medically acceptable excipient is selected in the case. In another embodiment of the invention, the immune response is A disease selected from, but not limited to, a group of influenza, HIV infection, and AIDS is improved by 2012 201219048. In another specific example of this month, the immune response is improved in an individual in need thereof. In another embodiment, the medically effective amount of the composition is in the range of from about 1 mg/kg of the individual body weight to about 1 mg/kg of the individual body weight. In another embodiment of the invention, the method is for Treating, preventing, and managing infections caused by pathogens in an individual. In another embodiment of the present invention, the pathogen includes avian virus and an HIV virus. In another specific embodiment of the present invention, the type of the virus is Η·, H3N2, X4 and R5 tropic Virus. In another embodiment of the invention, the individual is an animal or a human. The invention relates to a method for treating, preventing and managing a viral infection in an individual in need thereof, wherein The method comprises the step of administering to a subject a medically effective amount of a composition as an antiviral agent, the composition comprising a pentameric proanthocyanidin in a concentration ranging from about 55% w/w to about 99% w/w Astragalus, a terpolymer and a tetramer each in a concentration range of from about 0.5% w/w to about 35% w/w, and optionally a medically acceptable excipient. Another specific embodiment of the invention In an embodiment, the composition inhibits influenza A virus, X4 tropism and R5 tropic virus of HIV. In another embodiment of the invention, there is a medical composition, and the composition is at 4 1 mg/ Kg individual body weight to about 100 mg / kg body weight

In another embodiment of the present invention, the individual is an animal. The present invention relates to a method for treating, preventing, and managing a need for a reversal of a disease in a subject. The method comprises the step of administering to a subject a medically effective amount of a composition comprising: 55% w/w to about 99% w/w concentration percent of the pentameric proanthocyanidin flavonoids, each at about 0.5% w/w to about 35 °/. w/w concentration reference + terpolymers and tetramers within the X range, and optionally medically acceptable excipients. In the specific example of this month, the retroviral infection includes influenza A infection and HI V infection and AIDS. In another embodiment of the invention, the medically effective amount of the composition ranges from about 1 mg/kg of the individual body weight to about 1 mg/kg of the individual body weight. In another embodiment of the invention, the individual is an animal or a human. The present invention relates to a novel standardized composition derived from a vegetal source' which is standardized as 5 (%) to flaVa_d A (tetra) anthocyanin pentapolymer as shown in Fig. The present invention is also directed to a method for obtaining a new standard composition derived from a botanical therapeutic drug source which is standardized to 50% to 99% of a yellow-burning type A proanthocyanidin pentapolymer. The invention also relates to the use of a novel standardized composition derived from a vegetable source, which is standardized to 50% to 99% of the yellow-burning "proanthocyanidin pentapolymer" for use in prevention, treatment and HIV and influenza infection in Guan Wang. The present invention is also directed to the use of a new chemical composition derived from a plant source, which is standardized to 50% to 99% of the yellow appearance type A pre-ification. A phthalocyanine pentamer, which is used to elicit an improved immune response to an antigen in an individual in need thereof. In another embodiment of the invention, the immune response can be treated, managed or 18 201219048 in essence. In a specific example, the phytochemical source used to obtain the composition is Cinnamon, Litchi, and Peanut. In one embodiment of the invention, the novel-standardized composition derived from the plant source is standardized as Flavan A-type proanthocyanidin pentapolymer. In another specific example of the present invention, as shown in Figure 1, the pentamer has a molecular weight of 1440. In another embodiment of the invention, the composition comprises Five in the range of 50% to 99% In another embodiment of the invention, the composition comprises a dimer and a tetramer in the range of from 1% to 35%. In another embodiment of the invention, the composition is chromatographed in Figure 5. In another embodiment of the invention, the monomeric unit of the novel composition is selected from the group of edulis, preferably catechin or epicatechin. The invention is also directed to a method of making novel compositions by the processes described in this document. In a particular embodiment of the invention, the standardized composition comprises a medically acceptable excipient selected as appropriate. In another embodiment of the present invention, the excipient is selected from the group consisting of an added state sweetener, a coating agent, a binder, a disintegrant, a lubricant, a penicide, a suspending agent, a solvent, and a colorant. Groups of slip agents, anti-adhesives, antistatic oximes, surfactants, plasticizers, emulsifiers, perfumes, viscosity enhancers and antioxidants. 19 201219048 In the same as the specific example towel, the composition is formulated as liquid: powder, capsule, lozenge, injection, patch, ointment, gel, lotion cream lotion, tooth powder, spray and drip Dosage form. In still another embodiment of the invention, the composition is a powder or a liquid. Benxinyue is also a method for obtaining novel standardized and derived products derived from botanical sources, which standardizes $5〇% to exo% of flavanoids type A proanthocyanidin pentamers, wherein The method comprises the steps of: 1. grinding the vegetable material to a predetermined size; extracting with an organic, gluten agent to remove undesired toxic substances; 3. extracting the vegetable powder with deionized water; 4. using a two-stage layer The purification device is used for extract purification; 5. Drying, blending and screening to obtain 50. /. The composition of the flavanoid pentamer shown in Fig. 1 to 99% purity. The present invention is also directed to the use of a novel composition comprising an excipient as appropriate in the context of the present invention, which is used in the manufacture of a medicament for the treatment and management of mv and prophylaxis. Treatment and e-<IL drugs for influenza virus infection. The invention also relates to the use of a composition comprising an excipient as described in the present & month, which is used for the manufacture of a treatment for the treatment of an individual in need thereof, and for the prevention, treatment, and management of the infection. Influenza-infected medicines. The invention also relates to a composition comprising an excipient according to the invention, which is for the manufacture of a medicament for improving an immune response in an individual in need thereof. The invention also relates to the composition of the invention. It is used to induce an improved immune response in an individual in need. In another specific example of this month, the individual is an animal and a human. 201219048 ',; lw is derived from a novel standardized composition of plant origin Method, the composition

— ,, the product is quenched to 50% to 99% of the flavans A i is the phthalocyanine pentamer, and the K古 K initial method includes the following steps:

1. Grinding plant cinnamon apricot &# I, 彳4 is a technical peel or a nut with red seed coat. 2. Use a single consisting mainly of ethyl acetate, butyl acetate, amyl acetate or acetic acid. The solvent or a mixture of the above solvents (k is preferably si) solvent extraction material to remove fats and toxins as well as other aromatic compounds. This step is selected for the case of cinnamon; / 3. The extracted plant material is dried to remove the solvent; 4' is extracted with deionized water at pH 4 or a pH of between 3.8 and 5.8, preferably at pH 4.0. The two-stage chromatographic separation is used to carry out the extract 4 (four) for polar molecules and one for non-polar molecules; the adsorbed material is eluted with an alcohol solvent; 6. The eluted solvent is concentrated to a fine powder; 7. Dilute the hanked material with water and spray dry as appropriate to remove residual solvent. Characterized by 50%-99% pentamer 5. The novel composition obtained by the above process contains 1/0-35% dimer and 1%_35% tetramer and is pushed by means of the following examples as shown in the following example: 丨 4 L n L & The invention is illustrated. However, the examples are not to be considered as limiting the scope of the invention. Example 1

The average size of 1000 gm was immersed in 3000 ml of powdered cinnamon powder in the range of 3000 ml of acetic acid and poured into an extractor having a 200 mesh mesh bottom 21 201219048 screen. The bottom stripping agent is repeatedly recycled via the packed mass to achieve an effective extraction. Discard the eluent and remove the material from the extractor and force the air oven towel 3 〇. . Dry down. After the solvent is removed by drying, the material is reloaded into the extractor. The packaged material was extracted with 5000 liters of acidified deionized water at pH 4 and at 35. . The extract was recirculated through the bed over about 8 hours to achieve efficient extraction. The extract was filtered through a two-stage chromatography column to obtain a composition having 8% by weight of yellow, a type A proanthocyanidin pentamer (having a molecular weight of 144 Å): the extract was extracted by the first column to extract The relatively low polarity molecules in the material and the second stage chromatographic separation are used for relatively high polarity molecules in the composition. The resins used were the equivalents of XAD_1180& XAD_7Hp resin, respectively. The column was thoroughly washed with deionized water to make it free of adhesive material and the eluent was neutral. The column was further eluted with 175 ml of pure isopropanol and the collected eluent was concentrated under vacuum at 40 t and diluted with water and spray dried under the following conditions: Spray dryer: Cocurrent gas inlet temperature: 140 ° C outlet temperature 60 ° C atomizer RPM 14000 final weight of 5 丨 gm. Example 2 A powdered cinnamon powder having an average size of 1000 gm in the range of 16 mesh was immersed in 3000 ml of ethyl acetate and poured into an extractor having a 200 mesh mesh bottom 22 201219048 sieve. An effective extraction was achieved by recirculating the bottom stripping agent over the packaged material over a period of 10 hours. The eluent was discarded and the material was removed from the extractor and dried in a forced air oven at 30 °C. After the solvent is removed by drying, the material is reloaded into the extractor. The packaged material was extracted with 5 liters of acidified deionized water at pH 4.0 and the extract was recirculated through the bed for about 8 hours at 35 to achieve efficient extraction. The extract was filtered through a two-stage chromatography column to obtain 7 5 °/. The composition of the yellow type A proanthocyanidin pentapolymer (having a molecular weight of 144 Å). The extract is first passed through a first column to extract relatively low polarity molecules in the composition and the second stage chromatographic separation is used in relatively high polarity molecules in the composition. The resins used were equivalents of xAD_1180 and XAD_7Hp resins, respectively. The column was thoroughly washed with deionized water to make it free of adhesive material and the eluent was neutral. The column was again stripped with 250 ml of pure decyl alcohol and the collected eluate was below 40 in vacuo. Concentrate under the arm and dilute with water and spray dry under the following conditions: Spray dryer: Parallel flow inlet temperature: 145t: outlet temperature 60. (: The atomizer RPM 14 〇〇〇 final weight is 4,5 gm. Example 3 1 000 gm of powdered cinnamon powder with an average size of 16 mesh, soaked in 2500 ml of butyl acetate and Pour into the extractor of a porous bottom mesh with 2 mesh sieves. Repeat the extraction of the bottom eluate from the packaged material over 1 hour to achieve effective extraction. Discard the eluent and extract the extractor. 23 201219048 Remove the material and dry it in a forced air oven 3 (dry under rc) After removing the solvent by evaporation, refill the material in the extractor. Extract the encapsulating material with acidified deionized water at 3Gt: The extract was recirculated through the bed for about 12 hours to achieve an effective extraction. The extract was passed through a two-stage chromatography column to obtain 89% of a flavanoid type A phthalocyanine pentamer (molecular weight: 44 Å). The composition first passes the extract through the first column to extract relatively low polarity molecules in the composition and the second stage chromatographic separation is used to form relatively high polarity molecules of the composition. The resins used are XAD_m〇& The equivalent of XAD_7Hp resin. Deionized charge The column is decontaminated so that it is free of adhesive f and the eluent is neutral. The column is then stripped with 200 ml of pure ethanol and the collected eluate is concentrated under vacuum at 4 Gt and diluted with water and below. Spray drying under conditions: spray dryer: cocurrent flow

145〇C

60°C 14000 inlet temperature: outlet temperature

The final weight of the atomizer RPM is 4.8 gm. Example 4 The powdered cinnamon powder with an average size of 100 ggm in the range of (4) is soaked in 2500 ml of butyl acetate and poured into an extractor with a mesh screen. 'After 10 hours, the eluent from the bottom of the soil was re-routed through the packaged material to achieve an effective extraction 4 to the eluate and the material was extracted and dried in a forced air oven at 3 Torr. After the solvent is removed by evaporation, the material is refilled in the extractor. The packaged material was extracted with 5 liters of acidified detached water from 2012 2012048 sub-water and the extract was recirculated through the bed at 3 (rc) for about 12 hours to achieve efficient extraction. The extract was filtered through a two-stage chromatography column to obtain 99. % of the alkane-type A composition of the phthalocyanine pentamer (molecular weight M4 〇), first passing the extract through the first column to extract relatively low polarity molecules in the composition and the first stage Chromatographic separation is used for relatively high polarity molecules in the composition. The resin used is the equivalent of XAD-丨180 and XAD_7Hp resin, respectively. The column is washed thoroughly with deionized water to make it free of adhesive and the eluent is Neutral. The column was eluted with pure isopropanol and the collected eluate was concentrated under vacuum at 40 C and diluted with water and spray dried under the following conditions: Spray dryer: cocurrent air inlet Temperature: 1 4 5. (3

The outlet temperature is 6 (TC atomizer RPM 14000 is finally reset to 5 gm. Example 5 ιυυυgm average size in the 16 filaments of the 冈 』 八 八 八 八 八 师 μ The powder was immersed in 3 g of G 軚 ethyl ester and poured into an extractor having a 200 mesh mesh bottom screen. After about 8 hours, the day and the day were passed through the bottom of the package with the packaged material f. Achieving effectiveness: Take. Discard the eluent and remove the material from the extractor and dry it under forced air core 30 C. After removing the solvent by drying, refill the material in the extract. Acidify with 5000 ml. Ionized water is subjected to stroke reaction at ° F · 且 and is recirculated through the bed at 35 ° C for about 8 hours to obtain 25 201219048 effect extraction. Filtered by two-stage chromatography column Extracting a composition having 55% of a flavanoid type A proanthocyanidin pentamer (having a molecular weight of 144 Å) to pass the extract through the first column to extract relatively low polarity molecules in the composition and A two-stage chromatographic separation is used for relatively high polarity molecules in the composition. The resin used is the equivalent of XAD-1180 and XAD-7HP resin. The column is washed thoroughly with deionized water to make it free of adhesive and the eluent is neutral. Then use 175 ml of pure isopropanol to elute the tube. The column and the collected eluate were concentrated under vacuum at 40 ° C and diluted with water and spray dried under the following conditions: Spray dryer: cocurrent flow

Inlet temperature: 140 ° C Outlet temperature 60 t Nebulizer RPM 14000 The final weight is 2.5 gm. Example 6: Extraction from dried litchi peel: The dried litchi peel powdered with l〇〇〇gm was soaked in 5 ml ml of acidified water for 12 hours and clarified by filtration. The clarified filtrate was passed through a column containing an adsorption resin equivalent to XAD-1140 and XAD-7HP to separate polar and relatively non-polar compounds. The non-polar first column was eluted with ethanol and the eluate was concentrated to obtain a free-flowing powder with a yield of 5 〇〇 mgm. The second column containing all the polar substances alone was eluted with ethanol and concentrated to obtain 1 gm of the powder. When analyzed by HPLC, this fraction showed 85% of a flavanoid a-type proanthocyanidin pentamer (having a molecular weight of 144 Å). 26 201219048 Example 7. Peanut shell extraction from red skin with peanut seeds 1000 gm of dried peanut shell with red skin on seeds was immersed in 3.8 under 5000 ml volume of acidified water for a period of time and then filtered for clarification liquid. The clarified filtrate is passed through a column containing an adsorption resin equivalent to XAD_U4 and to separate polar and relatively non-polar compounds. The non-polar first column was eluted with ethanol and the eluate was concentrated to obtain a free-flowing powder with a yield of 20 gm. A second column containing all polar substances alone was eluted with ethanol and concentrated to obtain 500 mg of powder. When analyzed by HPLC, this fraction showed 82% of a flavanoid a-type proanthocyanidin pentapolymer (molecular weight of 1,440), as shown in FIG. Example 8: Purification to obtain flavanoid pentamers The powders separated by the procedure detailed in Examples 1-6 were dissolved in volume water and passed; The clarified liquid was treated with activated carbon at 60 C to decolorize the solution and clarified by filtration with a filter paper to remove all insoluble particles. The ruthenium solution thus obtained was taken twice by rubbing to remove all soluble solvents. And concentrated to obtain a powder. The powder was subjected to column chromatography on a reverse phase C-1 8 stone gel in a flash chromatograph using a 1% aqueous solution of formic acid and hydrazine. 1% methanolic acid. The following parameters were used. Equipment: Combiflash Companion column with variable UV detector: Redisep 12 gm (reverse phase ruthenium dioxide) Detection wavelength: 254 nm and 280 nm " Ratio. 1 8 m 1 / mi η Peak tube volume: 18 Ml peak width: 1 min 27 201219048

Threshold: 0.20 AU Solvent A: 〇. 1% aqueous formic acid Solvent B: 〇. 1% acetonitrile of decanoic acid The fractions numbered 1 to 19 are discarded. The collections numbered 2〇 to 22 were pooled and concentrated to obtain 256 gm of light brown powder. Tlc Screening Solvent System 〇" Sodium Acetate: Acetonitrile = 7:3 ratio, the resulting powder exhibits a UV absorption spot at 0.75 Rt after spraying with a large bacteriostatic/sulfuric reagent showing orange spots, which is considered to be proanthocyanidins. characteristic. The EI-MS (M-Η) (shown in Figure 2) ion peak at m/z 1439.9 corresponds to a plurality of intervals of the catechin structure corresponding to a total of five units (the molecular weight of the isolated compound of 288 heavy peaks) 144〇9. Confirmation by the coupling pattern that the configuration of the catechin unit is consistent with the configuration of epicatechin. A single peak of 2,3 cis stereochemistry in the flavan-3-ol unit (due to high molecular weight) The oligo causes the peak to broaden. The two signals between the four signals of δ4.84 to 4.91. Between the δ26 to 2 9 m peak broadening observed due to high molecular weight oligomeric properties The F-ring signal at the 4th position of the terminal unit _CH2 - ytterbium matrix "As for the two systems of ring B and e, the aromatic region signal is between δ 6.6 and 7.6. It can be seen at δ 100.9 The 13C carbon signal confirmed that the C2 carbon' and the 13C carbon signal visible at δ27·9 confirmed the C4 carbon, and the top ring C syndrome formed a double bond with the intermediate system ring, as shown in Fig. 3. The inclusion was obtained according to the above Examples 1 to 8. a trimerized proanthocyanidin flavonoid ranging from about 55% w/w to about 990/〇w/w, each of the terpolymers in a concentration range of from about 5% w/w to about 35% w/w and The composition of the polymer, and optionally the medically acceptable excipients. In addition, the in vitro and in vivo activities described in Examples 9 to 14 below were tested using the group 28 201219048. 9 · The effect of the test composition on the body fluid antibody price in the individual treated with cyclophosphamide (immune insufficiency) The Swiss albino mice (Riss albino mice) are divided into the treatment based on their treatment. Group 5, 6 animals per group. Day 0 'Used in physiological saline! x丨〇8 cells of sheep red blood cells (SRBC) were sensitized to all 5 groups. Standard drugs and test composition combinations Treatment of groups 2-5 for 8 days (days to days 7). On day 7, blood samples were collected from each of the 5 groups by posterior orbital puncture for determination of antibody titer. On the 7th day, after the blood was drawn, the mice were challenged by injecting 0.1 ml of SRBC into the athlete's foot. For 14 days, blood samples were collected from each small I by the posterior eye puncture for determination of secondary antibodies. The price of this test is as follows

Ring-awake amine 25 mg/kg, oral guanamine (25 mg/kg) composition (10 mg/kg), by! 0.33 0,33 Secondary HA power price on day 14 13.33 6.67 13.33 4 Cyclophosphamide (25 mg/kg piij^ composition (25 mg/kg), I-ring ring-filled amine (25 mg/kg) composition (50 mg/kg), oral 12 13.33 34.66 40 Humoral immunity acts as the first __ immunity increase makes the response to the infectious agent change and depends on many factors P; 5 lines and protects the host from infection. Protection of humoral pathogens Stronger. Individuals are dependent on factors. These factors include genetic composition 29 201219048 and individual medical history. Cyclophosphamide is a drug that suppresses the immune system. The use of this drug can identify the response of all animals evaluated in this study to antigen. As shown in the above table, the test composition reflects the immunological insufficiency of the individual - the secondary antibody and the increase in the antibody cost of the primary antibody. The primary antibody and the secondary antibody (the humoral immunity) are multiplied. This immune response is in response to the antigen, The presence of SRBC occurs and the immune response changes caused by pretreatment with cyclophosphamide are considered. Example 10: Test composition for peritoneal macrophages, blood multinucleated cells, swallowing activity, immune response to antigen The tube is effective, but further evaluation is needed to determine the effectiveness of the attack. The effectiveness of the ability to eliminate pathogens by immune response is assessed by assessing the ability of the phagocytic cells to respond to the ability to eliminate pathogens. The rats were divided into 3 groups of 6 animals each. A single dose of the control and the test composition were administered to each of the 3 groups. Each group was treated for 20 days and on the 21st day, the intraperitoneally received 5 still Cold-loaded saline buffered saline (PBS). Next, the peritoneal fluid was collected and the number of eucalyptus cells was counted using the WBC square in the illusion. The cell count per cubic millimeter was estimated. The remaining mice were kept continuously until the third day. And on the 29th day 'blood was taken from the posterior orbital plexus. Two drops of blood drawn from each mouse were placed on the slide and allowed to condense' and then placed in a moisturizing chamber, kept at 3rc for 25 minutes "These adherent cells It was incubated with the Candida albicans suspension and was observed by staining. Next, the number of cells ingesting the Candida suspension was counted. 30 201219048 Using the following formula Phagocytic index and phagocytosis %: 'phagocytic index = Candida in PMN Sai cover (the number of PMN cells involved in the total swallowing effect • % of phagocytosis = PMN cells ingesting Candida per 100 observed cells) Number of the above steps and the results are listed: Group treatment of peritoneal macrophage PMN cells phagocytic activity Candida/PMN average number Shows phagocytosis of PMN 1 Control 3558 ± 1361 2.185 Soil 0.34 81 ±3.88 2 Test composition g (25 mg/kg) 43.00 ± 1241 2.73 ± 0.37 95 ± 2.73 3 Test composition (50 mg/kg) 7758 ± 1512 1.901 0.48 92 ± 2.48 The above results show an increase in peritoneal macrophage count and phagocytic activity. The increased number of macrophages directly indicates an enhanced immune response to the antigen. Furthermore, the increased phagocytic activity of these macrophages indicates their effectiveness against the antigen. Example 11: The effect of the test composition on the resistance of the host against E. coli()-induced abdominal sepsis and the control and random Sexual Swiss albino mice were divided into test composition treatments. A single dose was administered to the mice for 28 days. On the third day, the mice were intraperitoneally injected with a suspension of E. coli containing 2.5 < 1 〇 9 cells in PBS. After the injection, the mortality of the mice was observed over 24 hours. The Guanlan 31 201219048 .J Hummer sepsis caused. The mortality of surviving animals was further speculated over 7 days. The results of this experiment are listed in the table below:

As can be seen from the above results, the mortality of the control and the lower dose test composition was infected by E. coli (the mortality rate was 1%. Under the test of the dose of 50 mg/kg, the mortality rate decreased by 63〇/ 〇 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与 与The test composition is displayed for the prevention of the host material, and the pretreatment of the test composition is used to reduce the mortality of the mice exposed to the disease, the Japanese, and the body. The ability of the pathogen to cause the wood to be affected by the body (including bacteria and viruses). This infection is caused by the composition of the material force -= a Langxin field, and the immune response caused by the organism in the presence of the pathogen is improved. And 2 is enough to control the number of pathogens, thereby preventing infection. Inhibition of Example 12: Type A epidemic stomach (bribe and face 2) virus This implementation: demonstrating the test composition inhibits the work of HmiAH3N2 virus: therefore it is used as a treatment "Protection and management of this disease The effectiveness of the method of infection. 32 201219048 The horse was inoculated into the 6-well plate (3xl05 cells per well), and the human sputum was infected with H1N1 and H3N2 viruses. After 3 days, the cells were infected with serial dilutions of <H1N1 and H3N2 virus for 1 hour, followed by 3 mL of the cover. The lip burst was added to each well. After 40 hours, the cells were fixed with 1% hydrazine for 1 hour. And stained with 1 〇/. crystal violet for 15 minutes. The viral valence was determined according to the plaque count. The susceptibility of the virus to the compound was determined by the plaque reduction test. Except that the compound of the private I was added to the covering medium. The procedure is similar to the plaque assay. The percent inhibition is calculated as [100-(VD/Vc)]xl00°/., where Vd and vc refer to the viral power in the presence and absence of the compound, respectively. Regression analysis of the dose-response curve generated by the plaque assay to calculate the minimum concentration of compound required to reduce the number of plaques by 50% (ec5〇) Sensitive virus strain (676) Resistant virus strain (6706) Test compound (pg/mL) 0 78.5 Π ~~ 25 40 7 50 25. 5 3.5 EQo 25.5 (17.7 nM) 36.1 (25 nM) Tamiflu (nM) This 50 4.5 &gt;5000~~ Test compound (pg/mL) H3N2 PFU inhibition ratio (%) 141.67 0 ~ — 110.33 22.11 57.33 59.53 — 27.67 80.47 ICsft 43.64 As apparent from the above table, infected cells treated with the test composition exhibited a significant reduction in plaque formation. In addition, the test composition exhibited a highly effective 33 201219048 against the Philippine-resistant strain of k Η丨N1, thus demonstrating its effectiveness as a possible treatment for epidemic i (Η1N1) disease infection. In addition, the second test showed that the compound was not inhibited and the Η3Ν2 virus strain of the influenza virus was effectively inhibited. Example 13. Effect of the test composition on the stimulated JJIV-1 (Χ4 tropic virus and R5 tropic virus) Obtained HIV 48 hours after transfecting the ΗΧΒ2 molecule pure line into 293 Τ cells] (ΗΧΒ2-Χ4 tropism) virus. The virus price is detected by instant pCR. Next, peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin (pHA) in 24 wells were infected with the virus. After 16-18 hours, the PBMCs were washed with phosphate buffered saline (PBS) and fresh RUS swe丨丨 Memorial lnstitute (RPMI) medium with 2% fetal bovine serum (FBS) was added. Cells and virus soup were collected on days 3, 5, and 7 (dpi) after infection. Test compositions and three standard drugs (AZT, AMD3100 and Tak_779) were tested in pBMC cells stimulated with HXB2 prion (μ virus and Rs virus) transfected hemagglutinin (pHA_2 pg/mL). The infection ❹ (M0I) was found to be 〇, 26. On day 3, day 5 and day 7 post infection, viral load detection was performed by RT_pCR as described above. , AMD3100 only showed inhibitory activity against CXCR4 nutritional virus (mean EC5〇=2.〇5 nM)' and Tak-779 only showed inhibitory activity against CCR5 nutritional virus (average Ε(:5〇=〇56 nM) Azt exhibits inhibitory activity against CCR5 nutrient virus and CXCR4 nutrient virus. The test composition exhibits 22.5 ^/mL (i5 625 nM) in the case of X4 virus &lt; 34 201219048 EC5 〇 value and is displayed in the case of R5 virus ECso value of 15 5 gg/mL (1〇77 nM). These values are comparable and in some cases more effective than the standard drug used. Examples 9-11 present the immunoreactive properties of the test composition, while examples 1 2-1 3 does not test the antiviral effect of the composition against mv and influenza virus (Η1N1). In summary, Example 9_丨3 indicates that the test composition is used to prevent infection by a two-pronged mechanism: Enhanced immune responses can act together as a protective or prophylactic option to prevent infection. Second, in the case of infection, 'the antiviral properties of the test composition reduce the viral load (both HIV and influenza)', allowing for enhanced immunity. Reaction elimination Infection and prevention of further damage. It is important to note that this immune response is only triggered in the presence of antigen. This is evidenced by the fact that no animal shows signs of inflammation and/or other symptoms associated with an over-activated immune system. This property makes it extremely suitable for long-term use as a prophylactic agent to prevent infection. The composition of the present invention contains not only a wide concentration range but also a concentration range of about 55% w/w to about 99% w/w. Anthocyanin flavonoids, each having a composition of terpolymers and tetramers ranging from about 0.5% w/w to about 35% w/w, improves the immune response. The effect of the composition on the immune response is specific. Concentration ranges from about 80% w/w to about 99% w/w of pentameric proanthocyanidin flavonoids, each having a concentration ranging from about 0.5% w/w to about 20% w/w concentration Better/excellent in the case of compositions of tetramers and tetramers. Example 14: Conceptual validation study for demonstrating the efficacy and safety of novel compositions in HIV and AIDS patients: 35 201219048 Not experienced in 4 Antiretroviral, asymptomatic sense of HUM&quot; Mechanized, placebo-controlled study. The test composition was studied in patients who had not experienced antiretroviral, asymptomatic HIV infection (with a (3) 4 count between 25 (M〇()/mm3). The test composition was tested at 3 mg/day and administered in a capsule form. Compared with the placebo: a placebo with a 67.28% increase in load, the test composition showed a decrease of 11.29% in the disease. There was a decrease in the CD4 count in both groups, but it was found that the composition of the composition #不★ and p 4 ^ was milk, and the percentage reduction of the LD4 was one and a half of the placebo (measured in the case of the composition 7 74 % decreased by 13 88% compared with placebo). Therefore, the test composition was found to be safe and effective relative to most vital organ functions and biochemical parameters. Example 14 details the ability of the test composition to inhibit viral load to confirm the antiviral effect of the test composition. Again, the improvement in WBC (CD4) counts is an important indicator of improved immune response compared to placebo. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the molecular structure of a flavonoid pentamer. Figure 2 shows the EI-MS of pentameric pentamers of flavonoids. Figure 3 shows the 13C NMR of the pentapolymer of the yellow-like substance. Figure 4 shows a flash chromatography of the composition to identify the flavonoid pentamers. Figure 5 shows the HPLC of the flavonoid pentamer. [Main component symbol description] None 36

Claims (1)

201219048 VII. The scope of application for patents: 1. The species, and the inclusions, which contain about 55% w/w to about 99% w/w concentration, are contained in the pentameric W anthocyanin yellow _, each in about Q 5 % w/w to about 35 〇 /. Dimers and tetramers in the range of w/w / □, and, where appropriate, medically acceptable excipients. 2. The composition of the patent 軏 丨 , , , , , , , , , , , , , , , , , , 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 3. The composition of claim 3, wherein the concentration of the proanthocyanidinoid ketone is preferably in the range of about 8% w/w to about 98% w/w, the polymer and The tetramers are each preferably in the range of from about 5% w/w to about 2% w/w. 4. The composition of claim 1, wherein the pentameric proanthocyanidin has a molecular weight of about 144 G; and the pentamer is a type A proanthocyanidin pentapolymer. 5' The composition of claim 1, wherein the excipient is selected from the group consisting of a gum, a granulating agent, a binder, a lubricant, a disintegrant, a sweetener, a colorant, a flavoring agent, A group of coating agents, plasticizers, antiseptic agents, suspending agents, emulsifiers, antistatic agents, and spheronizing agents. 6. The composition of claim 帛i, wherein the composition is formulated from the group consisting of a tablet, a sugar-coated tablet, an ingot, an aqueous or oily suspension, a dispersible powder or a granule, in a hard gel Various dosage forms of the group of emulsions, syrups and elixirs in capsules or soft gel capsules. 7. A method of preparing a composition comprising: about 55% w/w 37 201219048 to about 99% w/w concentration of pentameric proanthocyanidin yellow (tetra), each at about 0.5% w/ a trimer and a tetramer in the range of w to about 35% w/w. The method comprises the steps of: a) extracting the pulverized plant body with an organic solvent to remove toxic substances; b) drying the plant body Removing the organic solvent; c) re-extracting the dried plant body with an aqueous solvent to obtain an extract; and purifying the extraction and drying through a chromatography column to obtain the composition. The method of claim 7, wherein the powdered plant system is selected from the group consisting of plants belonging to the genus U. genus and the genus Peanut. The method of claim 7, wherein the organic solvent is selected from the group consisting of B ^ y acetonitrile, amyl acetate, 2-ethylhexyl acetate, and any combination; and the aqueous solvent It is acidified deionized water. = For example, if the method of applying for a patent is applied, the extraction (4) is carried out for a period of time ranging from about 1 hour to about 12 hours, preferably about 10 hours. 11 · If the patent application scope is included, go to a master The method, wherein the toxic substance comprises a sulphuric acid and an aldehyde. 12, as in the patent application scope, the method of the brother, wherein the extract is filtered through a two-stage chromatography column; ΧΑη and far chromatography column It is selected from the group consisting of XAD-U80, XAD-7HP Λ . ^ ^ 及 ^ and XAD ' ll 4 〇 resin. • For example, the method of the second-generation correction of the patent scope, the use of aqueous solvent μ further strokes are carried out at about 38 to about 4. ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; The time in the range of from about 8 hours to about i 2 hours, preferably about 1 hour, is carried out at a temperature in the range of from C to 40 C. 14. The method of claim 7, wherein the composition is further Included from the group consisting of gums, granulating agents, binders, lubricants, disintegrants, sweeteners, An excipient of a group of toners, flavoring agents, coating agents, plasticizers, preservatives, suspending agents, emulsifiers, antistatic agents, and spheronizing agents. a method comprising the step of administering to the individual a medically effective amount of a composition comprising a pentameric proanthocyanidin ranging from about 55./❶w/w to about 99% w/w concentration Astragalus, a terpolymer and a tetramer each in a concentration range of from about 0.5% w/w to about 35% w/w, and optionally a medically acceptable excipient. The method of item 15, wherein the immune response is improved in a disease selected from the group consisting of, but not limited to, influenza, HIV infection, and AIDS; and the immune response is improved in an individual in need thereof. The method of claim 5, wherein the medically effective stem composition ranges from about 1 mg/kg of the individual's body weight to about 100 mg/kg of the individual's body weight; and the method is for Treat, prevent, and manage infections caused by pathogens in this individual. The method of claim 5, wherein the pathogen comprises an influenza A virus selected from the group consisting of influenza viruses H1N1 and H3N2, and is selected from the group consisting of HIV X4 and R5 picvirus. A group of HIV viruses, such as the method of claim 15, wherein the individual is an animal or a human. 39 201219048 Therapeutic, preventive, and managing individuals in need, the method of viral infection includes the method of administering to the individual A medically effective amount of a step as a composition of an antiviral agent' composition comprising about 55% ▲ to about · w/" of the pentameric proanthocyanidins of the agricultural range, each of which is about 〇.5 %W/W to about 35% W/W of the trimer and tetramer in the garden, and optionally medically acceptable excipients. For example, the method of claim 2Q of the patent scope, wherein the composition inhibits the A-type snoring virus '(4) and the R5 tropic virus. True 22. The method of claim 2, wherein the medically effective amount of the composition ranges from about 1 mg/kg of the individual's body weight to about 100 mg/kg of the individual's body weight; and the individual is Animal or human. Nine methods for treating, preventing, and managing retroviral infections in an individual in need thereof, the method of IH comprising the administration of a medically effective amount of the composition to the individual, comprising 55% w/w Pentameric m-cyanin flavonoids in a concentration range of about 99% w/w, trimers and tetramers each in a concentration range of about G.5°/〇w/w to about 35% w/w And, as the case may be, a medically acceptable excipient. _ A method of claim 23, wherein the retrovirus susceptibility includes influenza A infection, HIV infection, and AIDS. 25. The method of claim 23, wherein the method is medically effective, and the composition is within about 1 mg/kg of the individual's body weight to about 1 〇〇 mg/kg of the individual's body weight and The individual is an animal or a human. 40