Anti-aging traditional Chinese medicine composition as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and discloses an anti-aging traditional Chinese medicine composition as well as a preparation method and application thereof. The composition is prepared from 12-24 parts of fructus lycii, 12-24 parts of raspberry, 12-15 parts of emblic leafflower fruit, 24 parts of rhizoma polygonati, 12-24 parts of pulp of dogwood fruit, 6 parts of folium mori and 9 parts of rhodiola rosea. The traditional Chinese medicine composition is guided by the theory of traditional Chinese pharmacology, follows the anti-aging core of reinforcing kidney, strengthening spleen and stomach and regulating liver pivot, is combined with clinical practice to screen traditional Chinese medicines with anti-oxidation and anti-inflammatory effects, and can tonify deficiency and strengthen body resistance. Clinical research proves that after the composition intervenes the HIV infected person for 3 months, the composition can significantly reduce the early apoptosis rate of peripheral T cells, improve the Ki67 proliferation index of CD4 + T cells and CD8 + T cells, relieve immune depletion, have no abnormal blood routine and liver and kidney functions, can improve clinical symptoms such as insomnia and weakness, improve the energy level of the body, and provide a safe and effective scheme for premature senility intervention of the HIV infected person.

Description

Technical Field

[0001] This application belongs to the field of traditional Chinese medicine technology, and in particular relates to an anti-aging traditional Chinese medicine composition, its preparation method and application. Background Technology

[0002] Although combined antiretroviral therapy (ART) has significantly improved the survival and life expectancy of people infected with Human Immunodeficiency Virus (HIV), patients receiving long-term ART still face a range of health challenges, among which premature aging is a significant factor affecting long-term survival and quality of life. HIV infection itself can initiate and continuously drive the accelerated aging process, a process that does not solely stem from the high viremia of late-stage AIDS but begins from the moment of initial HIV infection. Longitudinal cohort studies have found that only about 3 years after HIV infection, patients exhibit significant epigenetic aging acceleration and telomere shortening, and this effect is independent of changes in T cell subsets. These changes were not observed in age- and time-matched controls who were not infected with HIV, suggesting that HIV itself has a direct and early driving role in the epigenetic aging process.

[0003] Even with successful suppression of viral replication through antiretroviral therapy, HIV-infected individuals still exhibit immunosenescence-related characteristics, including a decreased proportion of immature T cells in peripheral blood, expansion of effector memory T cells, telomere shortening, and elevated expression of senescence-related genes CX3CR1 and CD57. Of particular note is that while chronic progressive HIV patients (those who can achieve long-term viral control without ART) experience slower HIV progression, they still exhibit immunosenescence markers similar to or even more severe than those treated with ART, such as CD8+. + A decreased naive / effect memory ratio and shortened telomeres in B and T cells indicate that even in the absence of clinically detectable viremia, the persistence of HIV itself can drive premature aging of the immune system. In older adults, the immunosenescence characteristics of HIV-infected individuals are further aggravated, manifested by low expression of IL-7Rα and effector memory CD8+ in high-dimensional T cell profiling analysis. +Significant expansion of T cell subsets was observed, accompanied by an increased proportion of cells expressing senescence, cytotoxicity, and inflammatory molecules such as CD57 and CX3CR1. Furthermore, ART drugs have been found to induce premature aging in vascular endothelial cells and astrocytes, manifesting as inflammation, oxidative stress, and abnormal cell function. HIV-infected individuals have a high incidence of age-related comorbidities, including metabolic disorders, cardiovascular disease, bone disease, neurological disease, liver and kidney disease, cancer, and frailty; the incidence of various non-AIDS-defined diseases is also on the rise. Premature aging has become a major factor affecting the quality of life and prognosis of HIV-infected individuals in the post-ART era, urgently requiring attention and resolution.

[0004] Currently, there is a lack of systematic and effective intervention programs for premature aging in HIV-infected individuals. Traditional Chinese medicine (TCM) has a rich heritage in anti-aging, based on theories such as "strengthening the kidneys, invigorating the spleen and stomach, and regulating the liver," and has accumulated rich clinical experience in delaying aging through treatments such as tonifying deficiency and supporting the body's vital energy, and regulating qi and blood. TCM herbs that are both food and medicine have the characteristics of high safety and few side effects, making them suitable for long-term use by HIV-infected individuals with weakened immune systems. Therefore, screening for TCM herbs with antioxidant and anti-inflammatory effects and constructing scientifically sound TCM combinations is of great significance for intervening in premature aging in HIV-infected individuals. Summary of the Invention

[0005] The purpose of this application is to overcome the shortcomings of the prior art and provide a safe and effective anti-aging traditional Chinese medicine composition for HIV-infected individuals, so as to alleviate the symptoms of immune aging and premature aging and improve their quality of life.

[0006] To achieve the above objectives, the embodiments of this application are implemented as follows: an anti-aging traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials in parts by weight: 12-24 parts of wolfberry, 12-24 parts of raspberry, 12-15 parts of amla, 24 parts of polygonatum, 12-24 parts of cornus officinalis, 6 parts of mulberry leaf, and 9 parts of rhodiola rosea.

[0007] Preferably, the anti-aging traditional Chinese medicine composition further includes 9 parts of Gynostemma pentaphyllum.

[0008] This application provides a method for preparing the above-mentioned anti-aging traditional Chinese medicine composition, comprising the following steps: Weigh each Chinese herbal medicine ingredient according to the specified weight, add water and decoct, then filter to obtain the filtrate; The filtrate was concentrated to obtain a clear extract; The extract is dried by spray drying or vacuum drying to obtain a fine powder of dry extract. Add excipients to the dry extract powder, granulate using dry granulation, wet granulation or one-step granulation process, dry and granulate to obtain granules corresponding to the anti-aging traditional Chinese medicine composition.

[0009] This application provides an example of the use of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating premature aging in HIV-infected individuals.

[0010] The anti-aging traditional Chinese medicine composition provided in this application is guided by traditional Chinese medicine theory and combined with clinical experience. It selects multiple traditional Chinese medicines with antioxidant and anti-inflammatory properties, which not only replenish deficiencies and strengthen the body's resistance, but also all originate from the list of medicinal and edible homologous substances published by the National Health Commission, ensuring safety and no toxic side effects. Clinical studies have confirmed that after 3 months of intervention in HIV-infected individuals, the traditional Chinese medicine composition of this application can significantly reduce the early apoptosis rate of peripheral T cells and significantly increase CD4 count. + T cells and CD8 + The T-cell Ki67 proliferation index alleviates immune exhaustion under viral suppression, and safety indicators such as blood routine, liver and kidney function are normal, indicating good overall safety. Furthermore, typical cases show that this composition can effectively improve clinical symptoms such as insomnia, fatigue, loss of appetite, abdominal distension and diarrhea in HIV-infected individuals, and enhance the body's energy levels. Attached Figure Description

[0011] Figure 1 The ATA infrared thermal imaging automatic detection result of a typical case 1 provided in the embodiments of this application; Figure 2 The ATA infrared thermal imaging automatic detection result of typical case 2 provided in the embodiments of this application; Figure 3 The ATA infrared thermal imaging automatic detection result of typical case 3 provided in the embodiments of this application. Detailed Implementation

[0012] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0013] The essence of traditional Chinese medicine (TCM) diagnosis and treatment lies in syndrome differentiation and individualized treatment. Anti-aging conditioning also follows this principle of personalized treatment. Therefore, the anti-aging TCM composition (Sanzi Anti-aging Formula) provided in this application is not static in clinical application. Instead, it is based on a core formula, and the ingredients and dosages are adjusted according to the patient's constitution, aging manifestations, and disease stage to achieve precise conditioning for each individual. This anti-aging formula is built around the three-dimensional anti-aging theme of "strengthening the kidney essence, invigorating the spleen and stomach, and regulating the liver." The core components have a clear compatibility logic. The basic formula is mainly divided into two core forms. The seven-ingredient basic formula consists of wolfberry, raspberry, amla, polygonatum, cornus officinalis, mulberry leaf, and rhodiola rosea. Among them, wolfberry, Raspberry and Cornus officinalis strengthen the kidneys, Polygonatum sibiricum invigorates the spleen and replenishes qi, mulberry leaf regulates the liver and promotes blood circulation, and Phyllanthus emblica and Rhodiola rosea invigorate blood and resolve phlegm. These seven herbs work together to construct an anti-aging framework that replenishes essence, invigorates qi, regulates the body's functions, and unblocks the meridians. The eight-herb enhanced formula adds Gynostemma pentaphyllum to the seven herbs. Gynostemma pentaphyllum enters the spleen and lung meridians and is good at invigorating qi and nourishing yin, as well as clearing heat and clearing heat. It can further enhance the "strengthening the spleen and stomach and aiding digestion" effect of the base formula, strengthen the nourishment of the innate essence by the acquired foundation, and is especially suitable for premature aging people with weak spleen and stomach function and poor energy metabolism. Although the number of herbs in the two base formulas differs, the core compatibility ideas are the same. They are both based on the principles of combining tonification and astringency, clearing and tonifying, and regulating cold and warm. They can be flexibly selected according to actual clinical needs, providing a solid foundation for subsequent diagnosis and modification.

[0014] Specifically, this application provides a base formula for an anti-aging traditional Chinese medicine composition, comprising at least the following parts by weight of traditional Chinese medicine raw materials: 12-24 parts of wolfberry, 12-24 parts of raspberry, 12-15 parts of amla, 24 parts of polygonatum, 12-24 parts of cornus officinalis, 6 parts of mulberry leaf, and 9 parts of rhodiola rosea.

[0015] Preferably, the anti-aging traditional Chinese medicine composition further includes 9 parts of Gynostemma pentaphyllum.

[0016] Preferably, the anti-aging traditional Chinese medicine composition comprises the following parts by weight of traditional Chinese medicine raw materials: 24 parts wolfberry, 12 parts raspberry, 12 parts amla, 24 parts polygonatum, 9 parts gynostemma pentaphyllum, 24 parts cornus officinalis, 6 parts mulberry leaf, 9 parts rhodiola rosea, 12 parts poria cocos, and 5 parts cinnamon.

[0017] Preferably, the anti-aging traditional Chinese medicine composition comprises the following parts by weight of traditional Chinese medicine raw materials: 24 parts wolfberry, 12 parts raspberry, 15 parts amla, 24 parts polygonatum, 12 parts cornus officinalis, 6 parts mulberry leaf, 9 parts rhodiola rosea, 12 parts dried tangerine peel, and 9 parts amomum villosum.

[0018] Preferably, the anti-aging traditional Chinese medicine composition is composed of the following traditional Chinese medicine raw materials in parts by weight: 12 parts of wolfberry, 24 parts of raspberry, 12 parts of amla, 24 parts of polygonatum, 12 parts of cornus officinalis, 6 parts of mulberry leaf, 9 parts of rhodiola rosea, 12 parts of jujube seed, 9 parts of polygala tenuifolia, and 12 parts of salvia miltiorrhiza.

[0019] Furthermore, this application provides a method for preparing the above-mentioned anti-aging traditional Chinese medicine composition, comprising the following steps: Weigh each Chinese herbal medicine ingredient according to the specified weight, add water and decoct, then filter to obtain the filtrate; The filtrate was concentrated to obtain a clear extract; The extract is dried by spray drying or vacuum drying to obtain a fine powder of dry extract. Add excipients to the dry extract powder, granulate using dry granulation, wet granulation or one-step granulation process, dry and granulate to obtain granules corresponding to the anti-aging traditional Chinese medicine composition.

[0020] Preferably, the excipient is one or more of lactose, maltodextrin, and magnesium stearate, and the amount of excipient used is 20%-50% of the weight of the dry extract powder.

[0021] Preferably, the step of weighing each Chinese herbal raw material by weight, adding water for decoction, filtering, and obtaining the filtrate includes: weighing each Chinese herbal raw material by weight, adding water for decoction twice; adding water twice for the first time, adding 8 times the volume of the total prescription amount of water and decocting for 1.5 hours; adding water twice for the second time, adding 6 times the volume of the total prescription amount of water and decocting for 1.5 hours; combining the two decoctions, filtering, and obtaining the filtrate. In examining the prescription extraction process conditions, this application uses a single prescription amount of medicinal slices and selects three factors—water volume, decoction time, and number of decoctions—for a three-factor, three-level orthogonal experiment. The water volume is selected as 6, 8, or 10 times the amount of raw herbs; the decoction time is selected as 30, 60, or 90 minutes; and the number of decoctions is selected as 1, 2, or 3 times. After the orthogonal extraction experiment was completed, the yield of the decoction and the contents of betaine, kaempferol-3-O-rutin and gallic acid were detected. Based on the test results, the optimal extraction conditions were determined to be: two extractions, the first with 8 times the amount of water of the prescription decoction pieces and extraction for 90 minutes, and the second with 6 times the amount of water of the whole prescription and extraction for 90 minutes.

[0022] Preferably, the step of concentrating the filtrate to obtain a clear paste includes: concentrating the filtrate under reduced pressure at a temperature of 60-70°C to a thick paste with a relative density of 1.10-1.15, filtering, and obtaining a clear thick paste. Since granules have specific requirements for solubility, a filtration step is added to the process to remove impurities. Comparison shows that the filtration effect is basically consistent when the relative density is 1.05-1.10, 1.10-1.15, and 1.20-1.25, and the solubility meets the requirements. However, when the relative density is 1.20-1.25, the loss of active ingredients is greater. Therefore, it is preferred that the Sanzi Anti-Aging Formula granules be concentrated under reduced pressure to a relative density of approximately 1.10-1.15 mg / ml, filtered, and then adjusted to a suitable density for drying method research.

[0023] Preferably, in the dry granulation process, the total amount of excipients is 20% of the weight of the dry extract powder (containing 19.5% maltodextrin and 0.5% magnesium stearate), and 5g of steviol glycosides are added per 1000g of granules; the granulation pressure is set at 30kg. This application previously investigated the granulation method, excipient types, excipient amounts, and granulation pressure: lactose, maltodextrin, and dextrin were selected as candidate excipients, and the granulation results were investigated when the excipient proportions were approximately 20%, 35%, and 50%, respectively; the granulation rate was also investigated at granulation pressures of 30 kg, 50 kg, and 70 kg. Based on the one-time granulation rate and combined with production costs, maltodextrin was selected as the filler. Given that the amount of maltodextrin has a relatively small impact on the one-time granulation rate, a 20% maltodextrin amount was ultimately selected; and 0.5% magnesium stearate was selected as the lubricant. Regarding granulation pressure, since different pressures have no significant effect on the granule formation rate, a lower pressure of 30 kg was selected. Furthermore, experimental results showed that when the amount of steviol glycosides added was 0.5%, the granules had suitable sweetness and a better taste.

[0024] Preferably, in the wet granulation process, the weight ratio of pharmaceutical powder to excipients is 1:1, the weight ratio of lactose to maltodextrin in the excipients is 2:1, 85% ethanol is used as a wetting agent, and the drying temperature is 60℃. This application previously investigated key indicators such as the type of excipients, the amount of excipients, the excipient ratio, and the concentration of the wetting agent for the wet granulation process, and also explored the effect of drying temperature on the moisture content of the particles. Based on the experimental results, the optimal process parameters for the wet preparation of Sanzi anti-aging granules were determined as follows: the ratio of pharmaceutical powder to excipients is 1:1, the excipients are lactose and maltodextrin (ratio 2:1), an appropriate amount of 85% ethanol is used as a wetting agent, and the drying temperature is set at 60℃. Based on the above-determined process parameters, three batches of small-scale sample granules were prepared, and key quality indicators such as particle yield, angle of repose, and moisture content were tested. The results showed that the particle yield of all three batches of samples was higher than 95%, and the particles had good flowability, with moisture content meeting relevant regulations.

[0025] Preferably, in the one-step granulation process, the inlet air temperature is 65-70℃, the inlet air volume is 75-85 m³ / h, the atomization pressure is 0.15 MPa, and the liquid supply speed is 10 r / min. This application initially used particle formability as the core evaluation index and systematically investigated the key parameters affecting one-step granulation, ultimately determining the optimal process conditions as: inlet air temperature 65~70℃, inlet air volume 75~85 m³ / h. 3 The atomization pressure was 0.15 MPa, and the liquid supply speed was 10 r / min. Based on these process parameters, three batches of small-scale sample particles were prepared, and the particle yield, flowability, and moisture content were tested. The results showed that the particle yield of all three batches was higher than 95%, the flowability was good, and the moisture content met the specified requirements.

[0026] Preferably, the dosage form of the drug is granules, and the dosage is 50mg once a day, taken with warm water, for a course of 12 weeks. Granules retain the advantages of decoctions, such as rapid absorption and fast action, while overcoming the disadvantages of decoctions, such as inconvenience in preparation, large dosage, and susceptibility to mold.

[0027] This application also provides an application of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating premature aging in HIV-infected individuals. The anti-aging traditional Chinese medicine composition is used to improve the symptoms of premature aging in HIV-infected individuals, including immune aging, T-cell depletion, increased early apoptosis rate, and clinical symptoms such as insomnia, fatigue, loss of appetite, abdominal distension, and diarrhea.

[0028] This application is guided by the theory of Traditional Chinese Medicine (TCM). The core of TCM anti-aging lies in a three-dimensional approach: "strengthening the kidney essence, invigorating the spleen and stomach, and regulating the liver." First, strengthening the kidney involves replenishing essence and marrow, warming kidney yang, and nourishing kidney yin to delay the decline of the hypothalamic-pituitary-target gland axis. Second, strengthening the spleen involves invigorating qi and promoting the upward movement of qi, aiding digestion and metabolism, and reducing oxidative stress. Third, regulating the liver involves regulating qi flow and nourishing liver blood. Women, whose physiological cycles of menstruation, pregnancy, lactation, and childbirth are particularly dependent on the abundance and proper flow of liver blood, and modern research has confirmed that the decline in liver-neuro-endocrine-immune network function is significantly correlated with aging phenotypes. Clinically, the focus is on "replenishing essence, invigorating qi, promoting blood circulation, resolving phlegm, and calming the mind." Early stage emphasizes liver regulation, mid-stage emphasizes spleen tonification, and long-term stage emphasizes kidney strengthening, combined with promoting blood circulation, removing blood stasis, resolving phlegm, clearing the meridians, and calming the mind to achieve simultaneous local and systemic anti-aging. The Three-Seed Anti-Aging Formula focuses on three main aspects: "strengthening the kidney essence, invigorating the spleen and stomach, and regulating the liver," while also incorporating five key elements: "replenishing essence, boosting qi, promoting blood circulation, resolving phlegm, and calming the mind." Goji berries, raspberries, and cornelian berries nourish the kidneys, working synergistically to replenish essence and astringe deficiencies, thus replenishing the body's innate constitution. Polygonatum and Gynostemma pentaphyllum nourish the spleen and lungs, boosting qi and yin, promoting the transformation of food essence, and strengthening the body's acquired constitution. Goji berries combined with mulberry leaves enter the liver meridian, replenishing liver blood and clearing deficiency heat. Phyllanthus emblica and Rhodiola rosea invigorate blood, cool the blood, clear the lungs, and resolve phlegm, treating both phlegm and blood stasis. Cornelian berries, Polygonatum, and Rhodiola rosea work together to astringe yin, strengthen yang, calm the mind, and calm the spirit, addressing symptoms such as night sweats, palpitations, and insomnia caused by premature aging. The entire formula combines tonification and astringency, clearing and tonifying, and regulating both cold and warm properties, making it suitable for premature aging-related symptoms such as deficiency of essence and qi, imbalance of yin and yang, and phlegm and blood stasis.

[0029] This application combines modern pharmacology to explore traditional Chinese medicines with anti-inflammatory and antioxidant functions. Its components are as follows: Lycium barbarum is rich in polysaccharides and flavonoids; its extract has a scavenging rate of DPPH, hydroxyl, and superoxide anion free radicals comparable to vitamin C, and can prolong the lifespan of model animals. Raspberry water extract can significantly increase the activity of SOD and CAT in the brain tissue of naturally aging rats, reduce MDA levels, shorten the escape latency in the Morris water maze, and improve learning and memory abilities. Its glycoprotein GP3 can also delay the aging of renal tubular epithelial cells by regulating oxidative stress indicators. Phyllanthus emblica ethanol extract significantly prolongs the lifespan of nematodes by increasing SOD and GSH-Px and inhibiting the accumulation of MDA and LPF. Polygonatum sibiricum polysaccharides can reduce the content of MAO-B and lipofuscin in the brain and liver of aging animal models; in the serum of menopausal rats, it increased SOD by 28% and reduced MDA by 35%, showing clear antioxidant and anti-aging effects. Total saponins from Gynostemma pentaphyllum can upregulate SOD and GSH-Px in D-galactose-aged mice, reduce MDA, and prolong average lifespan by 10.4%. Simultaneously, by activating Nrf2 / HO-1 and inhibiting the NF-κB pathway, they reduce ROS and protect vascular endothelial cells from oxidative stress-induced premature aging. Cornus officinalis, rich in ursolic acid, oleanolic acid, and flavonoids, can inhibit NLRP3 inflammasome activation, reduce the release of IL-1β, IL-6, and TNF-α, and significantly alleviate chronic inflammation. Mulberry leaf activates the NRF2 pathway, upregulates antioxidant enzymes such as SOD2 and NQO1, reduces ROS accumulation, repairs mitochondrial membrane potential, and alleviates oxidative stress damage. Rhodiola rosea glycosides can inhibit NF-κB and MAPK signaling, reduce LPS-stimulated macrophage secretion of CD40, NO, and TNF-α, and simultaneously increase the anti-inflammatory mediator IL-10, exerting an anti-inflammatory effect. It increases the activity of SOD and CAT in liver and brain tissues, reduces MDA levels, enhances the body's ability to scavenge free radicals, and delays oxidative aging.

[0030] The following detailed description, in conjunction with specific embodiments, illustrates the anti-aging traditional Chinese medicine composition, its preparation method, and its application. It should be noted that, unless otherwise specified, the experimental methods used in the following embodiments are conventional experimental procedures in the field; and the raw materials, equipment, and other consumables involved in the embodiments are standard products that can be routinely obtained through commercial channels, unless otherwise specified.

[0031] Example 1: Dry granulation preparation of anti-aging traditional Chinese medicine composition granules Raw material weighing: Weigh out 24g of wolfberry, 12g of raspberry, 12g of amla, 24g of polygonatum, 12g of gynostemma pentaphyllum, 12g of cornus officinalis, 6g of mulberry leaf, and 9g of rhodiola rosea by weight.

[0032] Extraction: Put the above-mentioned medicinal materials into an extraction tank, add 8 times the volume of water for the first time, decoct for 1.5 hours, filter to obtain the first filtrate; add 6 times the volume of water to the residue, decoct for 1.5 hours, filter to obtain the second filtrate; combine the two filtrates to obtain the total filtrate.

[0033] Concentration: The total filtrate is concentrated under reduced pressure to a thick paste with a relative density of 1.10-1.15 (60-70℃), filtered, and a clear thick paste is obtained.

[0034] Drying: The clarified thick paste is spray-dried (inlet air temperature 175℃, outlet temperature 70-90℃) to obtain a dry extract fine powder.

[0035] Granulation: Add 20% by weight of maltodextrin, 0.5% by weight of magnesium stearate and an appropriate amount of steviol glycosides (5g per 1000g of granules) to the dry extract fine powder, mix evenly, dry press into granules under 30kg pressure, dry and granulate to obtain granules.

[0036] Example 2: Preparation of anti-aging traditional Chinese medicine composition granules by wet granulation Raw material weighing: Weigh out 24g of wolfberry, 12g of raspberry, 12g of amla, 24g of polygonatum, 12g of gynostemma pentaphyllum, 12g of cornus officinalis, 6g of mulberry leaf, and 9g of rhodiola rosea by weight.

[0037] Extraction: Put the above-mentioned medicinal materials into an extraction tank, add 8 times the volume of water for the first time, decoct for 1.5 hours, filter to obtain the first filtrate; add 6 times the volume of water to the residue, decoct for 1.5 hours, filter to obtain the second filtrate; combine the two filtrates to obtain the total filtrate.

[0038] Concentration: The total filtrate is concentrated under reduced pressure to a thick paste with a relative density of 1.10-1.15 (60-70℃), filtered, and a clear thick paste is obtained.

[0039] Drying: The clear viscous paste is dried under vacuum (70°C) to obtain a fine powder of dry extract.

[0040] Granulation: Add excipients (lactose and maltodextrin in a weight ratio of 2:1) to the dry extract powder, the weight ratio of the powder to the excipients is 1:1, add an appropriate amount of 85% ethanol as a wetting agent, mix and granulate, dry at 60℃, and granulate to obtain granules.

[0041] Example 3: One-step granulation preparation of anti-aging traditional Chinese medicine composition granules Raw material weighing: Weigh out 24g of wolfberry, 12g of raspberry, 12g of amla, 24g of polygonatum, 12g of gynostemma pentaphyllum, 12g of cornus officinalis, 6g of mulberry leaf, and 9g of rhodiola rosea by weight.

[0042] Extraction: Put the above-mentioned medicinal materials into an extraction tank, add 8 times the volume of water for the first time, decoct for 1.5 hours, filter to obtain the first filtrate; add 6 times the volume of water to the residue, decoct for 1.5 hours, filter to obtain the second filtrate; combine the two filtrates to obtain the total filtrate.

[0043] Concentration: The total filtrate is concentrated under reduced pressure to a thick paste with a relative density of 1.18 (60°C), and mixed with an appropriate amount of maltodextrin and xylitol as a binder.

[0044] Granulation: Place the starch in the fluidization chamber of the one-step granulator, and adjust the inlet air temperature to 65-70℃ and the inlet air volume to 75-85m³. 3 The binder is sprayed at a liquid supply speed of 10 r / min with an atomization pressure of 0.15 MPa and a liquid supply speed of 10 r / min, causing the powder to condense into granules. After drying, the granules are sized to obtain granules.

[0045] The granules prepared in the above embodiments were subjected to clinical trials, as detailed below: 1. Objects and Methods 1.1 Research Design Study period: December 8, 2016 - May 9, 2017. Study location: Shenyang Sixth People's Hospital.

[0046] Research Methodology: A prospective, small-sample, self-controlled before-and-after study. The required sample size was estimated using the clinical superiority method, as shown in the following formula: (N = required sample size (number of patients); Zα = standard normal quantile corresponding to the one-sided significance level. If α = 0.05, the one-sided Zα is...) 0.05 =1.645; s = difference before and after intervention; =The average of the differences before and after the intervention), and according to the one-sided test design, 30 cases are planned to be completed.

[0047] 1.2 Research Subjects 1.2.1 Diagnostic criteria: The diagnostic criteria for the disease refer to the diagnostic criteria of the Ministry of Health's "Diagnostic Criteria for AIDS and HIV Infection" (WS293-2008) and the "Guidelines for the Diagnosis and Treatment of AIDS (2011 Edition)".

[0048] 1.2.2 Inclusion Criteria Meets diagnostic criteria: 1) Age 18-70, gender not limited; 2) Positive for HIV antibodies, confirmed by Western blotting test; 3) Received ART treatment for ≥6 months; 4) HIV RNA levels are below the detection threshold; 5) Absolute CD4 lymphocyte count ≥ 50 cells / μl; 6) Participate in this study voluntarily and sign an informed consent form.

[0049] 1.2.3 Exclusion Criteria: Applicants who meet the inclusion criteria but fall under any of the following conditions will be excluded. 1) Individuals with severe opportunistic infections that were not controlled prior to enrollment; 2) Patients who have been in or participating in other drug clinical trials within one month prior to enrollment; 3) WBC < 2 × 10 9 / L, N < 1.0 × 10 9 / L, Hb<90g / L, PLT<75×10 9 / L, abnormal liver and kidney function (abnormal liver function refers to AST or ALT or T-BIL ≥ 2 times the upper limit of the reference value, and abnormal kidney function refers to creatinine clearance rate lower than normal value). 4) Pregnant or breastfeeding women, or women planning to become pregnant; 5) Comorbid other serious diseases (such as tumors, cirrhosis, cardiovascular and cerebrovascular diseases, etc.); 6) Patients with intellectual or language impairments who cannot fully understand the test content or cooperate well.

[0050] 1.2.4 Exclusion Criteria: Suspension Criteria 1) Patients who develop severe opportunistic infections and require hospitalization for more than 2 months; 2) Patients who develop serious complications during clinical trials; 3) Those who experience serious adverse events or serious adverse reactions; 4) Violation of the test protocol; 5) Accidents; 6) Loss to follow-up; 7) Death; 8) Women who are found to be pregnant.

[0051] Researchers participating in clinical studies must carefully record the reasons for study termination and their relationship to the clinical study; for subjects who withdraw from the clinical study midway due to unwillingness to continue, the reasons must be clearly recorded, and the evaluation indicators at the time of termination must be recorded in detail.

[0052] 1.2.5 Exclusion Criteria 1) Subjects who should not have been enrolled but were enrolled include those who were mistakenly admitted, misdiagnosed, did not receive any medication, and have no testing records. (Excluded cases will not be included in efficacy statistical analysis. However, subjects who received at least one treatment and have at least one safety record should be included in adverse reaction analysis.) 2) Those that naturally fell off during observation, leaving no usable data; 3) Those who drop out of baseline due to reasons that prevent them from continuing treatment.

[0053] 1.3 Intervention Measures Research drug: Sanzi Anti-Aging Granules + Western Medicine Antiviral Treatment Plan Western medicine antiviral treatment: Zidovudine (AZT) + tenofovir (TDF) + lamivudine (3TC) + nevirapine (NVP) or efavirenz (EFV), or TDF + 3TC + lopinavir / ritonavir (Lpv / r), and individualized medication plans are formulated according to the patient's specific situation (such as viral load, immune system status, comorbidity, and tolerance to specific drugs).

[0054] Sanzi Anti-Aging Granules were provided by the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, and prepared according to the method in Example 1. Dosage: 50 mg once a day, taken with warm water 1 hour after taking antiviral drugs. The course of treatment is 12 weeks.

[0055] The period during which a patient uses the medication is defined as the "exposure period," while other periods when the patient does not use the medication are defined as the "control period." The impact of medication use on the patient is assessed by comparing changes in laboratory indicators in the same patient during these two periods.

[0056] 1.4 Statistical Methods: This study used R4.3.0 software for statistical analysis. Measurement indicators were expressed as mean and standard deviation. Differences in measurement indicators before and after treatment were calculated. Paired t-tests were used for differences following a normal distribution, while Wilcoxon rank-sum tests were used for differences not following a normal distribution. Hypothesis testing consistently used two-tailed tests. The test statistics and their corresponding p-values ​​are provided. P <0.05 is considered statistically significant.

[0057] 2 Results Analysis 2.1 General Information The 30 subjects were from the Sixth People's Hospital of Shenyang City from December 8, 2016 to May 9, 2017. Nine subjects were found to be ineligible for inclusion and were promptly excluded. The general information of the remaining 21 subjects is shown in Table 1.

[0058] Table 1 General Information of Subjects 2.2 Therapeutic Indicators Table 2. Changes in immune function indicators before and 3 months after oral administration. Table 3. Changes in aging indicators before and 3 months after oral administration. Note: p<0.05, p<0.01, p<0.001 This study included 21 HIV patients admitted to the Sixth People's Hospital of Shenyang City between December 8, 2016 and May 9, 2017. Among them, 17 were male (80.95%) and 4 were female (19.05%). The age distribution was concentrated in the 30-59 age group, accounting for 81.0% (17 / 21), with the 40-49 age group accounting for the highest proportion (38.09%, 8 / 21). Patients aged ≥60 years and 30-39 years each accounted for 19.05%. There were no patients under 18 years old or aged 18-29 years old.

[0059] Table 2 shows that after 3 months of oral administration of Sanzi Anti-Aging Granules and 3 months of intervention, CD3... + CD3 + CD4 + and CD3 + CD8 + The absolute counts all increased slightly, but the differences were not statistically significant; CD4 + / CD8 + The ratio increased from 0.35 to 0.40, but this did not reach a significant level. CD45RA + With CD45RO + The changes in the number of subpopulations were not significant. This suggests that short-term intervention did not significantly alter the total number of peripheral T cells or the distribution of their subpopulations.

[0060] Table 3 shows the early apoptosis marker Annexin V in HIV patients 3 months after oral administration of Sanzi Anti-Aging Granules. + / PI - The value decreased from 6.00 (4.35-11.20) to 2.50 (1.85-3.80), a statistically significant difference (z = 3.180, P = 0.001); Annexin V, a marker of late apoptosis / necrosis. + / PI - The trend was downward, but no statistically significant difference was observed. Furthermore, CD4... + T cell Ki67 proliferation index increased significantly, from 5 (3.5-7.5) to 12 (7-23) (z = 3.285, P = 0.001), CD8 + The Ki67 proliferation index of T cells increased from 5±4 to 14±8 (t = -4.557, P<0.001).

[0061] 2.3 Safety Indicators Blood routine, urine routine, liver and kidney function and other indicators were normal.

[0062] 3. Discussion and Conclusion Three months after intervention with Sanzi Anti-Aging Granules, early apoptosis of peripheral T cells in HIV-infected individuals (Annexin V) + / PI -The significant decrease in CD4+ suggests that the drug inhibits HIV-related activation-induced cell death and reduces T cell depletion; simultaneously, CD4+... + Ki67 + With CD8 + Ki67 + The proportions increased to 2.4-fold and 2.8-fold from baseline, respectively, suggesting enhanced IL-7 / IL-15-mediated homeostatic proliferation. Loss decreased while proliferation increased, and CD4... + and CD8 + The absolute count remained stable, and short-term intervention alleviated immune exhaustion under the background of viral suppression, providing preliminary cellular-level evidence for delaying premature HIV aging.

[0063] Although the Sanzi Anti-Aging Granules did not significantly affect the total number and subset distribution of peripheral T cells in HIV patients, they effectively inhibited early apoptosis and increased the Ki67 proliferation index, with good overall safety. This suggests that they have the potential to improve T cell depletion and delay premature aging in HIV patients.

[0064] The following is an implementation case based on clinical data.

[0065] Typical Case 1 Mr. Li, male, 26 years old, visited the hospital on April 15, 2009.

[0066] [Chief Complaint] HIV infection for 9 years, chronic insomnia, fatigue, and poor appetite.

[0067] [Present Illness] The patient was diagnosed with HIV infection at the local CDC in March 2000 and began antiretroviral therapy at the end of 2002. The most recent CD4 cell count was 320 cells / µL, and the plasma HIV load was <50 copies / ml. The patient is thin, suffers from chronic insomnia, chest tightness, shortness of breath, fatigue, and poor appetite. Recently, the patient has experienced chills, a feeling of coldness in the lower abdomen, a red tongue tip, a thin white coating, and a weak pulse.

[0068] The following traditional Chinese medicine decoction is prescribed: 24g of wolfberry, 12g of raspberry, 12g of amla fruit, 24g of polygonatum rhizome, 9g of gynostemma pentaphyllum, 24g of cornus fruit, 6g of mulberry leaf, 9g of rhodiola rosea, 12g of poria cocos, and 5g of cinnamon bark, totaling 14 doses. Usage: One dose daily, decocted in water and taken warm, 200mL per dose.

[0069] [Treatment Process] On April 29, 2009, after taking the above prescription for 14 days, the patient reported improved sleep, reduced nightmares, significantly improved fatigue, increased appetite, and disappearance of the cold sensation in the lower back and abdomen. The tongue tip was red, the coating was thin and white, and the pulse was thready and weak. An ATA infrared thermography report was reviewed (…). Figure 1The average temperature in the projection areas of the liver, spleen, stomach, and small intestine in the middle jiao increased by 0.3-0.6℃, while the temperature in the kidney and bladder areas in the lower jiao increased by 0.2-0.3℃. The calorific value distribution was symmetrical, and the thermal sequence level was concentrated in the 1-2 grades, indicating that the local energy in the middle and lower jiao increased, mainly in the liver, spleen, kidney, and bladder.

[0070] Typical Case 2 Mr. Li, male, 49 years old, visited the hospital on April 9, 2009.

[0071] [Chief Complaint] HIV infection for 4 years, with long-term abdominal distension, diarrhea and fatigue.

[0072] [Present Illness] The patient was diagnosed with HIV infection at the local CDC in October 2005 and began antiretroviral therapy in 2005. The most recent CD4 cell count was 465 cells / ul, and the plasma HIV load was <50 copies / ml. Since 2008, the patient has experienced abdominal distension and discomfort, which is more pronounced after eating. Diarrhea occurs 3-4 times daily, with loose stools. Occasional dull abdominal pain is also present. The patient prefers hot drinks, experiences fatigue, and is drowsy. The tongue is dark with a pale white coating and teeth marks on the edges. The pulse is slippery.

[0073] The following traditional Chinese medicine decoction is prescribed: 24g of wolfberry, 12g of raspberry, 15g of amla, 24g of polygonatum, 12g of cornus officinalis, 6g of mulberry leaf, 9g of rhodiola rosea, 12g of tangerine peel, and 9g of amomum villosum. A total of 14 doses are recommended. Dosage: One dose daily, decocted in water and taken warm. Dosage: 200mL per dose.

[0074] [Clinical Process] On April 23, 2009, after taking the above prescription for 14 days, the patient's fatigue and abdominal distension improved, and diarrhea lessened to 1-2 times per day. The tongue was pale red with a thin white coating, and the pulse was slippery. An ATA infrared thermography report was reviewed. Figure 2 The average temperature of the projection areas of the lungs, spleen, and small intestine in the upper and middle jiao was increased by 0.1-0.3℃. The calorific value distribution was symmetrical, and the thermal sequence level was concentrated in the 1-2 level, indicating that the local energy in the upper and middle jiao increased, mainly in the lungs, spleen, and small intestine.

[0075] Typical Case 3 Mr. Jiang, male, 30 years old, visited the hospital on April 9, 2009.

[0076] [Chief Complaint] HIV infection for 3 years, with long-term abdominal distension, diarrhea, fatigue, and poor sleep.

[0077] [Present Illness] The patient was diagnosed with HIV infection at the local CDC in August 2006 and began antiretroviral therapy in 2006. The most recent CD4 cell count was 360 cells / µL, and the plasma HIV load was <50 copies / ml. The patient experiences long-term abdominal distension, which worsens after eating, and belching. Other symptoms include fatigue, insomnia, frequent dreams, and easy awakening at night. The tongue is purplish-dark with a thick yellow coating, and the pulse is thready.

[0078] The following traditional Chinese medicine decoction is prescribed: 12g of wolfberry fruit, 24g of raspberry fruit, 12g of amla fruit, 24g of polygonatum rhizome, 12g of cornus fruit, 6g of mulberry leaf, 9g of rhodiola rosea root, 12g of jujube seed, 9g of polygala root, and 12g of salvia root. A total of 14 doses are prescribed. Usage: One dose is decocted in water and taken warm, 200mL per dose.

[0079] [Clinical Process] On April 23, 2009, after taking the above prescription for 14 days, the patient's abdominal distension improved, fatigue lessened, sleep duration increased, and dreams decreased. The tongue was pale and dark with a thin white coating, and the pulse was thready. An ATA infrared thermography report was reviewed. Figure 3 The average temperature of the projection areas of the upper jiao (lung), middle jiao (spleen), and double large intestine increased by 0.2-0.4℃, with symmetrical calorific value distribution and thermal sequence level concentrated in level 1-2, indicating a local increase in energy in the upper and middle jiao, mainly in the lungs, spleen, and large intestine.

[0080] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of this patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. An anti-aging traditional Chinese medicine composition, characterized in that, Includes the following Chinese herbal raw materials by weight: 12-24 parts of wolfberry, 12-24 parts of raspberry, 12-15 parts of amla, 24 parts of polygonatum, 12-24 parts of cornus officinalis, 6 parts of mulberry leaf, and 9 parts of rhodiola rosea.

2. The anti-aging traditional Chinese medicine composition according to claim 1, characterized in that, It also includes 9 portions of Gynostemma pentaphyllum.

3. The anti-aging traditional Chinese medicine composition according to claim 1, characterized in that, The anti-aging traditional Chinese medicine composition consists of the following parts by weight of traditional Chinese medicine raw materials: 24 parts wolfberry, 12 parts raspberry, 12 parts amla, 24 parts polygonatum, 9 parts gynostemma pentaphyllum, 24 parts cornus officinalis, 6 parts mulberry leaf, 9 parts rhodiola rosea, 12 parts poria cocos, and 5 parts cinnamon.

4. The anti-aging traditional Chinese medicine composition according to claim 1, characterized in that, The anti-aging traditional Chinese medicine composition consists of the following parts by weight of traditional Chinese medicine raw materials: 24 parts wolfberry, 12 parts raspberry, 15 parts amla, 24 parts polygonatum, 12 parts cornus officinalis, 6 parts mulberry leaf, 9 parts rhodiola rosea, 12 parts dried tangerine peel, and 9 parts amomum villosum.

5. The anti-aging traditional Chinese medicine composition according to claim 1, characterized in that, The anti-aging traditional Chinese medicine composition consists of the following parts by weight of traditional Chinese medicine raw materials: 12 parts of wolfberry, 24 parts of raspberry, 12 parts of amla, 24 parts of polygonatum, 12 parts of cornus officinalis, 6 parts of mulberry leaf, 9 parts of rhodiola rosea, 12 parts of jujube seed, 9 parts of polygala tenuifolia, and 12 parts of salvia miltiorrhiza.

6. A method for preparing an anti-aging traditional Chinese medicine composition as described in any one of claims 1-5, characterized in that, Includes the following steps: Weigh each Chinese herbal medicine ingredient according to the specified weight, add water and decoct, then filter to obtain the filtrate; The filtrate was concentrated to obtain a clear extract; The extract is dried by spray drying or vacuum drying to obtain a fine powder of dry extract. Add excipients to the dry extract powder, granulate using dry granulation, wet granulation or one-step granulation process, dry and granulate to obtain granules corresponding to the anti-aging traditional Chinese medicine composition.

7. The method for preparing the anti-aging traditional Chinese medicine composition according to claim 6, characterized in that, The process involves weighing each herbal ingredient according to its weight, adding water to decoct, filtering, and obtaining a filtrate, which includes: Weigh each Chinese herbal medicine ingredient according to the specified weight, add water and decoct twice. For the first decoction, add 8 times the volume of water of the total prescription and decoct for 1.5 hours. For the second decoction, add 6 times the volume of water of the total prescription and decoct for 1.5 hours. Combine the two decoctions, filter, and obtain the filtrate.

8. The method for preparing the anti-aging traditional Chinese medicine composition according to claim 6, characterized in that, The process of concentrating the filtrate to obtain a clear extract includes: The filtrate was concentrated under reduced pressure at a temperature of 60-70°C to a thick paste with a relative density of 1.10-1.15, and then filtered to obtain a clear thick paste.

9. The method for preparing the anti-aging traditional Chinese medicine composition according to claim 6, characterized in that, The dry granulation process meets the following conditions: the total amount of excipients is 20% of the weight of the dry extract powder, and the excipients include maltodextrin, magnesium stearate, and steviol glycosides; wherein maltodextrin accounts for 19.5% of the total weight of the excipients, magnesium stearate accounts for 0.5% of the total weight of the excipients, and steviol glycosides, after being converted according to the total weight of the excipients, are added at a rate of 5g per 1000g of granules; the granulation pressure is set at 30kg. The wet granulation process meets the following conditions: the weight ratio of drug powder to excipients is 1:1, the weight ratio of lactose to maltodextrin in the excipients is 2:1, 85% ethanol is used as a wetting agent, and the drying temperature is 60℃. The one-step granulation process meets the following conditions: air inlet temperature is 65-70℃, air inlet volume is 75-85m 3 / h, atomization pressure is 0.15MPa, and liquid supply rotation speed is 10r / min.

10. The use of a traditional Chinese medicine composition for anti-aging as described in any one of claims 1-5 in the preparation of a medicament for treating premature aging in HIV-infected individuals.

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