CN114632132B - Traditional Chinese medicine composition for activating and eliminating latent HIV, and preparation method and application thereof - Google Patents

Traditional Chinese medicine composition for activating and eliminating latent HIV, and preparation method and application thereof Download PDF

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CN114632132B
CN114632132B CN202011486844.3A CN202011486844A CN114632132B CN 114632132 B CN114632132 B CN 114632132B CN 202011486844 A CN202011486844 A CN 202011486844A CN 114632132 B CN114632132 B CN 114632132B
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CN114632132A (en
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鲁自云
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Guangzhou Ruyuan Biotechnology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/25Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258Panax (ginseng)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/13Coniferophyta (gymnosperms)
    • A61K36/14Cupressaceae (Cypress family), e.g. juniper or cypress
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232Angelica
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282Artemisia, e.g. wormwood or sagebrush
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/34Campanulaceae (Bellflower family)
    • A61K36/346Platycodon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484Glycyrrhiza (licorice)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/75Rutaceae (Rue family)
    • A61K36/752Citrus, e.g. lime, orange or lemon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/78Saururaceae (Lizard's-tail family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/884Alismataceae (Water-plantain family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/906Zingiberaceae (Ginger family)
    • A61K36/9068Zingiber, e.g. garden ginger
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • A61P31/18Antivirals for RNA viruses for HIV
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps

Abstract

The invention relates to a traditional Chinese medicine composition for activating and eliminating latent HIV, a preparation method and application thereof, belonging to the technical field of traditional Chinese medicines, wherein the active ingredients of the traditional Chinese medicine composition comprise the following medicinal materials in parts by weight: 7-10 parts of red ginseng, 10-12 parts of angelica sinensis, 8-10 parts of dried ginger, 10-16 parts of biota orientalis leaves, 11-14 parts of mugwort leaves, 10-15 parts of platycodon grandiflorum, 20-22 parts of dried orange peel, 7-8 parts of cordate houttuynia, 5-9 parts of rhizoma alismatis and 10-12 parts of liquorice. The composition is used for treating AIDS patients, has the dual effects of activating and clearing HIV latent virus library, and is expected to realize functional cure of AIDS.

Description

Traditional Chinese medicine composition for activating and eliminating latent HIV, and preparation method and application thereof
Technical Field
The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for activating and eliminating latent HIV, and a preparation method and application thereof.
Background
Human immunodeficiency virus (Human Immunodeficiency Virus, HIV) is an RNA retrovirus that attacks the human immune system. It invades the most important CD4+ T lymphocytes in the immune system of the human body, damages the cells in large quantities, gradually loses the immune function of the human body, and causes AIDS (Acquired Immune Deficiency Syndrome, AIDS). By 2020, HIV-1 has caused nearly 5,000 deaths worldwide and causes pain. The most effective method of treating AIDS clinically has remained as high-potency antiretroviral therapy (HAART) which converts AIDS from a fatal disease to a chronic controlled disease. Although HAART is effective in blocking HIV replication and preventing AIDS from developing, AIDS patients need to accept HAART for their life to control the virus, and once HAART is discontinued, the virus will rebound rapidly, resulting in this phenomenon due to the presence of a pool of latent viruses in the body. In one aspect, activated CD4+ T cells are infected with HIV and the reverse transcribed DNA fragment is transported into the nucleus and integrated into the host cell DNA, and the integrated viral gene is transcribed, translated and packaged, thereby replicating the virus in large quantities and continuing to infect the next cell. On the other hand, a small fraction of non-activated cd4+ T cells, also known as resting cd4+ T cells, are not expressed in the cell by provirus, although infected by the virus, and are dormant. Proviruses are generally classified into proviruses and postintegrating viruses, wherein the proviruses are isolated from the cytoplasm, so that viral genome replication is hindered and the persistent infectious threat of the virus is small; the level of transcription of the integrated virus is limited by various factors, and viral proteins and viral particles cannot be formed. If these proviral genes are permanently silenced, they will not naturally infect other cells. Unfortunately, resting cells can also be reactivated and once activated by antigen stimulation, viral dormancy continues to replicate new viruses. HAART only inhibits plasma viruses and infection-activated cd4+ T lymphocytes, whereas resting cells have a longer half-life and are ineffective. Resting CD4+ T cells are considered to be the most prominent pool of latent viruses for HIV, and in addition, macrophages, monocytes, dendritic cells, hematopoietic stem cells, astrocytes, central nervous system, genital tract, intestinal mucosa, gut associated lymphoid tissues, etc. have been studied to find the existence of a pool of latent HIV. Therefore, to achieve complete cure of aids, not only the plasma viral pool needs to be cleared, but also latent viruses in tissues and cells need to be prevented.
The persistence of the latent viral pool is the biggest obstacle in curing aids. To eliminate the persistent infection pool, the most studied strategy is to combine therapies that induce latent HIV expression with persistent HAART to prevent new cell infection while enhancing clearance of the infected cells, now recognized by the production of viral antigens by the infected cells. This method of activating latent infection followed by killing is also known as a "block and Kill" treatment strategy.
Researchers have developed HIV Latency Reversers (LRAs) to accomplish the first step in this process by inducing viral expression in the host. Since viral latency is driven by host cell programming, LRAs must be directed to host processes, current research on LRAs is largely divided into three major categories: (1) Epigenetic modifications (e.g., histone deacetylase inhibitors, DNA methylase inhibitors, histone methyltransferase inhibitors); (2) Transcription factors (e.g., protein kinase C activator, P-TEFb activator); (3) Cytokine immune function modulators (e.g., IL-7, retinoic acid). Ideally, LRAs would also enhance clearance mechanisms to facilitate reduction of the reservoirs, but should at least not interfere with viral clearance. Few studies have paired LRAs with viral clearance strategies, representing an early state of the art.
Current viral clearance strategies mainly include therapeutic vaccines, CAR-T and neutralizing antibodies, and the like. Therefore, if a method for activating the HIV latent virus library and eliminating the HIV virus can be developed, a new idea is provided for curing HIV.
Disclosure of Invention
Based on the above, it is necessary to provide a traditional Chinese medicine composition for activating and eliminating latent HIV, which has the dual functions of activating and eliminating the latent HIV library at the same time, and is expected to realize functional cure of aids.
A traditional Chinese medicine composition for activating and eliminating latent HIV comprises the following medicinal materials in parts by weight: 7-10 parts of red ginseng, 10-12 parts of angelica sinensis, 8-10 parts of dried ginger, 10-16 parts of biota orientalis leaves, 11-14 parts of mugwort leaves, 10-15 parts of platycodon grandiflorum, 20-22 parts of dried orange peel, 7-8 parts of cordate houttuynia, 5-9 parts of rhizoma alismatis and 10-12 parts of liquorice.
In conventional therapies, western medicine is more focused on inhibiting viral replication, while traditional Chinese medicine is focused on modulating immunity. HAART and opportunistic infection resistance therapy in Western medicine play an important role in reducing the death rate of illness, but also have the problems of withdrawal rebound, drug resistance, serious toxic and side effects and the like.
The Chinese medicine considers that the pathogenesis of AIDS is that the exterior is due to invasion of pathogenic factors, the interior is due to deficiency of vital energy and is the syndrome of deficiency and excess, and the disease location relates to viscera such as liver, spleen, kidney and the like. On the one hand, the five zang organs have weak qi, blood, yin and yang, on the other hand, the defending external function is not firm and is easy to invade by exogenous pathogenic factors, which have different wind-cold summer-heat and damp-dryness-fire; on the other hand, the five zang organs are damaged, so that the pathogenesis changes such as phlegm-fluid retention, water dampness, qi stagnation, blood stasis, wind and fire transformation are easy to occur. The inventor finds that aiming at complex lesions of AIDS, the characteristics of integral regulation and diagnosis and treatment of traditional Chinese medicine can be utilized, the multi-target and bidirectional regulation immunity effect is exerted, and the method is complementary and perfect to HIV/AIDS prevention and treatment means.
The inventor leans out heart blood for many years, based on the palace imperial prescription of Song dynasty, the traditional Chinese medicine composition is developed according to the pathogenic theory of 'warm', 'epidemic' theory, 'consumptive disease' and the like of traditional Chinese medicine, combines a great deal of clinical practice, adjusts compatibility, and organically combines the traditional Chinese medicine theory with modern pharmacological research.
Wherein, the red ginseng is dried root and rhizome of ginseng after steaming, and the processed ginseng not only can reduce water content, but also can kill enzyme activity, thereby playing the role of enzyme killing and glycoside preserving. After processing, the red ginseng contains more ginsenoside and more relative content than the sun-dried ginseng, but the content of the common components is not greatly different. The main active ingredients of Ginseng radix Rubri are ginsenoside, and effective components such as saccharide, amino acid, polypeptide, trace elements, etc. Red ginseng has pharmacological effects of resisting tumor, diabetes, aging, fatigue, etc.
The Chinese angelica is perennial herb of Umbelliferae, and has effects of replenishing blood, promoting blood circulation, regulating menstruation, relieving pain, moistening dryness, and smoothing intestine. Pharmacological studies at home and abroad show that: the angelica polysaccharide has obvious promotion effect on immune regulation system and hematopoietic system, has anti-tumor, antiviral, antioxidant and radioprotective effects, and has protection effect on organism.
The Platycladus orientalis belongs to evergreen arbor of Platycladus genus of Cupressaceae family. The biota orientalis leaves are dried branches and leaves of biota orientalis, are cold in nature, bitter and astringent in taste, can be used as an efficacy drug for cooling blood, dehumidifying, detumescence, hair growth, hair blacking and the like, and mainly comprise biotone, quercetin, fennel ketone, volatile oil and the like.
The mugwort leaf is Ai Gansao leaf of Compositae plant, also known as BINGTAI, herba Yingcao, moxibustion grass, etc., is a traditional Chinese medicine in China, mainly contains volatile oil, flavonoid, phenylpropanoids, terpenoid, etc., and has various pharmacological effects of resisting bacteria, resisting viruses, stopping bleeding, resisting tumors, protecting liver, easing pain, resisting inflammation, resisting oxidation, relieving cough and asthma, etc.
Radix Platycodi is dry root of radix Platycodi of Campanulaceae. Has effects of dispersing lung qi, relieving sore throat, eliminating phlegm, and expelling pus. Can be used for treating cough with excessive phlegm, chest distress, pharyngalgia, hoarseness, pulmonary abscess, and pus discharge.
The pericarpium Citri Tangerinae is dried mature pericarp of Citrus reticulata Blanco of Rutaceae and its cultivar. Is a common Chinese medicinal material, and has the effects of regulating qi, soothing liver, eliminating dampness, strengthening spleen, relieving qi stagnation of spleen and stomach, and eliminating phlegm and dampness.
Herba Houttuyniae is dry aerial part of houttuynia cordata Thunb of Saururaceae. Yu xing Cao is pungent in flavor, cold in nature and cool in nature, and enters lung meridian. Has effects in clearing away heat and toxic materials, relieving swelling, treating sore, promoting urination, removing dampness, clearing heat, relieving dysentery, invigorating stomach, and resolving food stagnation, and can be used for treating lung abscess, pyocutaneous disease, hematochezia, spleen and stomach heat caused by excessive heat, toxic heat, damp evil, and disease heat.
The Alismatis rhizoma is dry tuber of Alismatis rhizoma of Alismataceae. The theory of traditional Chinese medicine considers that it has cold nature and has the efficacy of promoting diuresis and removing dampness. Modern medical research shows that alisma can reduce serum total cholesterol and triacylglycerol content and slow down atherosclerosis; alismatis rhizoma and its preparation are also used for treating Meniere's disease, dyslipidemia, spermatorrhea, fatty liver, diabetes, etc.
Glycyrrhrizae radix is plant of Glycyrrhiza genus of Leguminosae family, and comprises three kinds of Glycyrrhrizae radix of Ural, glycyrrhiza glabra and Glycyrrhiza distention, and its root and rhizome are used as medicines. Sweet taste, mild nature, and good effect in restoring heart, lung, spleen and stomach channels, glycyrrhrizae radix has effects of invigorating spleen and replenishing qi, clearing heat and detoxicating, eliminating phlegm and relieving cough, relieving spasm and pain, harmonizing various medicines, etc., and can be used for treating spleen and stomach weakness, listlessness debilitation, palpitation and short breath, cough with excessive phlegm, gastric and abdominal, limb spasm and pain, carbuncle swelling and sore, and relieving drug toxicity and intensity. Detoxification is one of the most important effects of licorice, 60% of traditional Chinese medicine prescriptions contain licorice, and licorice is one of the most widely used medicines in traditional Chinese medicine. Liquorice is classified as 'superior', and the liquorice is considered to be capable of relieving the toxicity and the intensity of other medicines, and long-term clinical practice also proves that the liquorice can effectively reduce toxicity, relieve toxic symptoms and reduce death rate.
In the prescription of the traditional Chinese medicine composition, the red ginseng is used for reinforcing primordial qi, strengthening body resistance and consolidating foundation, and enabling qi to be exuberant and defending evil, so that the traditional Chinese medicine composition is a monarch drug. The dried ginger and the mugwort leaf warm the middle energizer to dispel cold, the Chinese angelica enriches the blood and harmonizes the blood, the three medicines are mutually combined, the blood is warm and then goes, and the assistant monarch drug harmonizes qi and blood of the whole body and is used as ministerial drug. The biota orientalis, the houttuynia cordata and the rhizoma alismatis cool blood and reduce swelling, promote diuresis and remove turbidity, so that damp toxin and turbid phlegm remove vital energy and safety; pericarpium Citri Tangerinae and radix Platycodi are used as adjuvant drugs for regulating qi and dispersing, and qi-flowing and dampness-resolving. So that liquorice is used for harmonizing various medicines.
Thus, the medicines in the whole formula are compatible, both qi and blood are compatible, so that the healthy qi is kept inside, the damp turbidity is removed outside, and the effects of tonifying qi, nourishing qi, promoting diuresis and removing turbidity are achieved.
In modern medicine, ginseng and angelica can improve hypodynamia, and the main components of the ginseng saponin, ginseng polysaccharide, angelica polysaccharide and the like can activate T, B lymphocyte, macrophage and other immune cells, promote cytokine production, promote antibody production and play a multi-aspect regulation role on the immune system. Activation of cytokines such as IL-2 and IL-7 activates cells, and then phosphorylates the C-terminal of STAT5 to activate STAT5 homo-or hetero-dimers STAT5A and STAT5B, and further activate transcription factors such as NFAT to promote transcription initiation of HIV, thus activating a latent viral pool of HIV.
The Chinese arborvitae twig, the mugwort leaf, the oriental waterplantain rhizome and the like mainly contain components for killing viruses, assist organisms to kill HIV viruses, and treat complications such as herpes, canker sore and the like caused by AIDS.
Dried orange peel, cordate houttuynia, licorice and the like can strengthen stomach, promote digestion, relieve vomiting and diarrhea by dried ginger, and is favorable for improving diarrhea, anorexia and other complications caused by AIDS, thereby increasing the weight of patients and improving physique.
Thereby realizing the double functions of activating and clearing the HIV latent virus library and achieving better treatment effect.
In one embodiment, the active ingredients of the traditional Chinese medicine composition comprise the following medicinal materials in parts by weight: 9 parts of red ginseng, 11 parts of Chinese angelica, 9 parts of dried ginger, 13 parts of cacumen biotae, 12 parts of mugwort leaf, 12 parts of platycodon grandiflorum, 20 parts of dried orange peel, 8 parts of cordate houttuynia, 7 parts of rhizoma alismatis and 11 parts of liquorice.
In one embodiment, the Chinese medicinal composition further comprises pharmaceutically acceptable auxiliary materials.
The invention also discloses a preparation method of the traditional Chinese medicine composition, which comprises the following steps:
red ginseng powder preparation: taking red ginseng in a separated amount, and crushing to obtain red ginseng powder for later use;
preparing extract: decocting the rest materials except Ginseng radix Rubri in water, filtering, and concentrating the filtrate to obtain extract;
granulating: adding the red ginseng powder into the extract, adding pharmaceutically acceptable auxiliary materials, and granulating to obtain the red ginseng extract.
In one embodiment, in the step of preparing the extract, water is added for 2 times of decoction, and the filtrates are combined.
In one embodiment, the pharmaceutically acceptable excipients include sucrose and dextrin.
The invention also discloses application of the traditional Chinese medicine composition in preparing medicines for treating AIDS.
In one embodiment, the agent is used to activate latent virus of HIV and simultaneously clear HIV.
Compared with the prior art, the invention has the following beneficial effects:
the invention relates to a traditional Chinese medicine composition for activating and eliminating latent HIV, which is a monarch drug with the effects of reinforcing primordial qi, strengthening body resistance and consolidating constitution, and enabling qi to be exuberant and self-energy to defend against pathogenic factors. The dried ginger and the mugwort leaf warm the middle energizer to dispel cold, the Chinese angelica enriches the blood and harmonizes the blood, the three medicines are mutually combined, the blood is warm and then goes, and the assistant monarch drug harmonizes qi and blood of the whole body and is used as ministerial drug. The biota orientalis, the houttuynia cordata and the rhizoma alismatis cool blood and reduce swelling, promote diuresis and remove turbidity, so that damp toxin and turbid phlegm remove vital energy and safety; dried orange peel and platycodon root are used as adjuvant drugs for regulating qi and freeing, and qi transformation and dampness transformation; so that liquorice is used for harmonizing various medicines. Thus, the medicines in the whole formula are compatible, both qi and blood are compatible, so that the healthy qi is kept inside, the damp turbidity is removed outside, and the effects of tonifying qi, nourishing qi, promoting diuresis and removing turbidity are achieved. The composition is used for treating AIDS patients, has the dual effects of activating and clearing HIV latent virus library, and is expected to realize functional cure of AIDS.
Drawings
FIG. 1 is a graph showing the trend of the HIV viral load of each group in example 2;
FIG. 2 is a schematic diagram showing the results of the viral load test in example 3;
FIG. 3 is a section view (4X) of normal lymph node of infected monkey # 608 in example 3;
FIG. 4 is a view (4X) of a lymph node section before treatment of the infected monkey No. 608 in example 3;
FIG. 5 is a view (4X) of a lymph node section of the treated infected monkey No. 608 in example 3;
FIG. 6 is a view of lymph node sections (4X) of example 3 after 8 weeks of withdrawal from infection with monkey # 608.
Detailed Description
In order that the invention may be readily understood, a more complete description of the invention will be rendered by reference to the appended drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The inventor conducts intensive clinical research and mechanism exploration on the traditional Chinese medicine composition, and discovers that the composition has the dual functions of activating and clearing HIV latent virus library simultaneously through clinical experiments and monkey model experiments, and is hopeful to realize functional cure of AIDS.
Example 1
A Chinese medicinal composition for activating and eliminating latent HIV comprises the following components: 9 parts of red ginseng, 11 parts of Chinese angelica, 9 parts of dried ginger, 13 parts of cacumen biotae, 12 parts of mugwort leaf, 12 parts of platycodon grandiflorum, 20 parts of dried orange peel, 8 parts of cordate houttuynia, 7 parts of rhizoma alismatis and 11 parts of liquorice.
The traditional Chinese medicine composition is prepared by the following method:
red ginseng powder preparation: taking the red ginseng with the prescription amount, crushing and weighing the red ginseng powder to obtain red ginseng powder for standby;
preparing extract: decocting the rest 9 materials except Ginseng radix Rubri in water twice, filtering, mixing filtrates, and concentrating the filtrate to appropriate amount to obtain extract;
granulating: adding the red ginseng powder into the extract, adding a proper amount of sucrose and dextrin, and granulating (1 g of granules is equivalent to 1.9g of the total amount of crude drugs) to obtain the traditional Chinese medicine composition for activating and eliminating latent HIV, which is named as "like source one".
Example 2
In cooperation with the public health research center of kenya, 100 clinical trials were conducted in the medical research center of kenya using the drug (e.g., source one) obtained in example 1, and all the participants were positive for HIV-1, informed consent was obtained and a related agreement was signed. The medicine is randomly divided into 2 groups, wherein the medicine is taken by the first group, 15 g/time and 3 times a day; the second group took the same dose of placebo. A dosing cycle of 22 months was performed.
In the experimental process, the HIV virus is detected by adopting an international detection method, and the result is shown in figure 1.
FIG. 1 shows the trend of the viral load of each group of HIV, and it can be seen from the graph that the trend of the virus of the experimental group of patients taking the drug of the present invention is a rising and falling trend. The viral load reached peak at 3 months and then declined, with progressive decrease in viral load as the test progressed. The viral load of the control group increased rapidly after a period of time (after the start of the test, all aids were on demand for HARRT treatment to control the virus, and after the start of the test, only the product was taken).
The above experimental results show that the traditional Chinese medicine composition of the invention can activate HIV latent virus in a short time, then clear HIV virus, and maintain low viral load.
Example 3
Rhesus animal model test.
In order to research the mechanism of activating HIV latent virus library of the product, experiments of feeding 15 monkeys for 2 months and observing drug withdrawal for 2 months are carried out, and the anti-monkey immunodeficiency virus (SIV) and the effect of treating AIDS monkeys of the drug are evaluated.
An experimental method.
1. Experimental animals:
15 rhesus monkeys were all male. Weight 4.43-6.73kg,4-6 years old, healthy appearance, no superficial lymphadenectasis after physical examination, serologically tested SIV, monkey retrovirus D (SRV) and monkey T lymphocyte I virus (STLV-I) antibodies negative, tuberculin negative, dysentery bacteria negative, animals were provided by Guangdong primate laboratory animal center.
Infection strain and dose: SIVmac239,5MID100 (5 100% monkey infection dose) 1ml was intravenously injected. Infection was performed according to the conventional method, and 15 monkeys were infected in total.
2. Drug and experimental treatment regimen:
the 15 infected monkeys were randomly divided into 3 groups (5 monkeys per group) of low dose (equivalent to clinical trial), high dose (equivalent to 2-fold clinical trial), and SIV control groups. Treatment was started 71 days after infection, and the drug treatment group was converted to monkey drug administration dose as the human drug and dose in example 1. The low dose group is administered at a dose of 1.875 g/kg/day, the high dose group is administered at a dose of 3.75 g/kg/day, and the aqueous suspension is prepared, and the administration is carried out 1 time a day, the administration is continuous for 8 weeks, the middle is continuous, and the observation is continued for 8 weeks after stopping the administration. The SIV control group is a non-treatment group, the stomach is irrigated with an equivalent amount of physiological saline for 8 weeks continuously, and all the observation index test groups are the same as the control group.
3. Viral load experimental results.
The virus load level of the infected monkey plasma was measured by fluorescent quantitative PCR multiplex well, and the results are shown in FIG. 2. As can be seen from the figure, there was an increase in viral load following treatment in both the high and low dose groups, log in the high dose group after 4 weeks of administration 10 RNA was raised 0.53 on average, low dose group Log 10 The average rise of RNA is 0.38, and the RNA is slightly reduced after stopping drug rather than during treatment; log of contemporaneous control group 10 The average increase in RNA was 0.36, and the control viral load was continuously rising, higher after drug withdrawal than before and during treatment, and the high dose group also maintained lower levels of viral load after 2 months of drug withdrawal without significant rebound. Therefore, the product has certain effects of activating and controlling viruses.
3. Lymph node biopsy experimental results.
One inguinal lymph node was obtained by aseptic surgery after infection (before treatment), the other inguinal lymph node and the other axillary lymph node were obtained after 8 weeks of treatment and drug withdrawal observation, and were fixed in 4% neutral formaldehyde solution, paraffin embedded, and the morphology of the case was observed by HE staining rear-view mirror. The results show the evaluation as shown in the following table.
TABLE 1 comparison of treatment of SIV infected monkey lymphadenopathy
The above results show that the low dose group at the time of treatment, the 4 monkey lymph node structures were degenerated at the beginning of treatment, and then transformed into the proliferative type (i.e., lymph nodes were in the proliferative state with immunopotentiating effect), and overall evaluated as "transformed good"; the lymph node structure of 3 monkeys in the high-dose group is always kept in a proliferation type immunity enhancement state, and can be kept stable after stopping the medicine. One of the 5 monkeys in the control group was overall evaluated for one, one was well-transferred, and the remaining three were leveled, but the average was maintained for the regression, indicating failure to excite immune function.
Lymph node sections from one of the monkeys (number 608) at different times in the high dose group are exemplified below.
Fig. 3 is a view of normal lymph node sections of a monkey before infection, fig. 3 is a view showing 4×by HE staining, and from fig. 3, 10×by HE staining, it can be seen that lymph nodes are slightly reduced, cortex is thinned, lymphatic follicles are reduced, mantle layer is thin, germinal centers are slightly reduced, immunoblast cells are still active, and the evaluation is "hyperplasia-degeneration".
Fig. 4 is a view of a lymph node section before treatment of an infected monkey, fig. 4 is a view showing the HE staining 4×schematic, and from the view showing the HE staining 10×schematic of fig. 4, it can be seen that the lymph node is slightly reduced, the lymph follicle is slightly reduced, the mantle layer is thickened, the germinal center is slightly reduced, and the immunoblast is active, and the evaluation is "hyperplasia-degeneration".
Fig. 5 is a view of a lymph node section after treatment of an infected monkey, fig. 5 is a view showing 4 x of HE staining, and from fig. 5 is a view showing 10 x of HE staining, it can be seen that lymph nodes slightly increase, cortex thickening is obvious, lymphatic follicles increase and increase, mantle thickening, germinal centers increase, immune blast cells are active, and the evaluation is "hyperplasia".
Fig. 6 is a view of lymph node sections 8 weeks after drug withdrawal in infected monkeys, fig. 6 is a view of HE staining 4 x, and from the view of fig. 6, HE staining 10 x, it can be seen that lymph nodes are slightly contracted, cortex is thickened, lymphatic follicles are obviously increased, mantle layer is thickened, germinal centers are increased, immune blast cells are active, and the evaluation is "hyperplasia".
The results show that the medicine has the effect of activating viruses and can enable the structure of lymph nodes to be in a hyperplastic immune enhancement state.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims (8)

1. The traditional Chinese medicine composition for activating and eliminating latent HIV is characterized in that the active ingredients of the traditional Chinese medicine composition are prepared from the following medicinal materials in parts by weight: 7-10 parts of red ginseng, 10-12 parts of angelica sinensis, 8-10 parts of dried ginger, 10-16 parts of biota orientalis leaves, 11-14 parts of mugwort leaves, 10-15 parts of platycodon grandiflorum, 20-22 parts of dried orange peel, 7-8 parts of cordate houttuynia, 5-9 parts of rhizoma alismatis and 10-12 parts of liquorice.
2. The traditional Chinese medicine composition for activating and eliminating latent HIV according to claim 1, wherein the active ingredients of the traditional Chinese medicine composition are prepared from the following medicinal materials in parts by weight: 9 parts of red ginseng, 11 parts of Chinese angelica, 9 parts of dried ginger, 13 parts of cacumen biotae, 12 parts of mugwort leaf, 12 parts of platycodon grandiflorum, 20 parts of dried orange peel, 8 parts of cordate houttuynia, 7 parts of rhizoma alismatis and 11 parts of liquorice.
3. The traditional Chinese medicine composition for activating and eliminating latent HIV according to claim 1, further comprising pharmaceutically acceptable excipients.
4. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, comprising the following steps:
red ginseng powder preparation: taking the red ginseng with the prescription amount, and crushing to obtain red ginseng powder for standby;
preparing extract: decocting the rest materials except Ginseng radix Rubri in water, filtering, and concentrating the filtrate to obtain extract;
granulating: adding the red ginseng powder into the extract, adding pharmaceutically acceptable auxiliary materials, and granulating to obtain the red ginseng extract.
5. The method according to claim 4, wherein in the step of preparing the extract, water is added to decoct for 2 times, and the filtrates are combined.
6. The method of claim 4, wherein the pharmaceutically acceptable excipients comprise sucrose and dextrin.
7. Use of the Chinese medicinal composition according to any one of claims 1-3 in the preparation of a medicament for treating aids.
8. The use of a Chinese medicinal composition according to claim 7, wherein the medicament is for activating latent viruses of HIV and simultaneously clearing HIV.
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中医药治疗艾滋病进展;吴蓓蓓等;《浙江中西医结合杂志》;20131231;第23卷(第4期);第333-335页,尤其是第334页左栏第5段 *

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