Traditional Chinese medicine formula for preventing and treating Parkinson's disease and preparation method thereof

Abstract

The traditional Chinese medicine formula comprises the following components in parts by mass: 100 parts of fructus alpiniae oxyphyllae, 100 parts of ramulus uncariae cum uncis, 100 parts of rhizoma nardostachyos, 100 parts of radix paeoniae alba, 70 parts of radix achyranthis bidentatae, 70 parts of xylaria nigripes, 70 parts of polygala japonica, 70 parts of conic gymnadenia tuber, 70 parts of herba cistanche, 70 g of radix scutellariae, 40 parts of scorpion and 40 parts of sea snake. The traditional Chinese medicine composition is prepared on the basis of the traditional Chinese medicine compatibility theory, treats both symptoms and root causes and has good prevention and treatment effects on Parkinson's disease through experimental verification.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a traditional Chinese medicine formula for the prevention and treatment of Parkinson's syndrome and its preparation method. Background Technology

[0002] Parkinson's disease (PD) is a serious neurodegenerative disease affecting the health of middle-aged and elderly people. Its motor symptoms include resting tremor, rigidity, bradykinesia, and postural instability. Currently, the etiology of idiopathic Parkinson's disease is not fully understood, but it is generally believed to be related to aging, genetics, and environmental factors. The reduction of dopamine neurons in the substantia nigra and striatum of the brain is closely related to the development of the disease. In Traditional Chinese Medicine (TCM), Parkinson's disease is classified as a tremor syndrome, characterized by deficiency in the root and excess in the branch, with deficiency primarily affecting the liver, kidneys, and spleen, while excess manifests as wind, fire, phlegm, and blood stasis. Western medicine plays a dominant role in the treatment of Parkinson's disease, but TCM adjunctive therapy can effectively reduce the dosage of dopamine preparations and mitigate the mental problems, motor complications, impulse control disorders, and sleep disturbances associated with Western medicine, such as hallucinations, delusions, confusion, and cognitive impairment. Combining TCM and Western medicine can leverage their respective strengths and compensate for their weaknesses, maximizing the treatment effect.

[0003] Patent CN 111407853 B discloses a traditional Chinese medicine composition for treating Parkinson's disease and its preparation method, including Rehmannia glutinosa, Epimedium, Astragalus membranaceus, Cistanche deserticola, tortoise shell, earthworm, Gastrodia elata, Salvia miltiorrhiza, Ligusticum chuanxiong, Angelica sinensis, and Paeonia lactiflora. This traditional Chinese medicine composition mainly nourishes the liver and kidneys and invigorates qi and blood. It is suitable for patients with obvious symptoms of liver and kidney deficiency and qi and blood deficiency, with deficiency symptoms but not severe wind. It has a low effect on extinguishing wind and stopping spasms and a poor effect on resolving phlegm and calming the mind.

[0004] Patent CN 106963913 B discloses a traditional Chinese medicine for the adjunctive treatment of Parkinson's disease and its preparation method, including Cistanche deserticola, Lindera strychnifolia, Alpinia oxyphylla, Dioscorea opposita, Paeonia lactiflora, and Uncaria rhynchophylla. This traditional Chinese medicine formula mainly focuses on warming kidney yang and nourishing liver blood, with a focus on warming and tonifying, consolidating and astringing, and relatively mild effects in extinguishing wind and stopping spasms. It is suitable for patients with insufficient kidney yang and concurrent liver blood deficiency. It has poor effects in resolving phlegm and calming the mind, and has no effect in promoting blood circulation and unblocking collaterals. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a traditional Chinese medicine formula for the prevention and treatment of Parkinson's syndrome, so as to solve the problems of patients with obvious wind-movement symptoms (severe tremors) and phlegm-heat or restlessness and heat symptoms.

[0006] The objective of this invention is achieved through the following technical solution: a traditional Chinese medicine formula for the prevention and treatment of Parkinson's syndrome, comprising, by weight, 100 parts of Alpinia oxyphylla, 100 parts of Uncaria rhynchophylla, 100 parts of Nardostachys chinensis, 100 parts of Paeonia lactiflora, 70 parts of Achyranthes bidentata, 70 parts of Codonopsis pilosula, 70 parts of Panax quinquefolius, 70 parts of Codonopsis pilosula, 70 parts of Cistanche deserticola, 70g each of Scutellaria baicalensis, 40 parts of Buthus martensii, and 40 parts of sea snake.

[0007] A method for preparing a traditional Chinese medicine formula for the prevention and treatment of Parkinson's syndrome includes the following steps: S1. Weigh out the Chinese medicinal materials according to the specified proportions, mix them together, and process them into 600-1000 mesh ultrafine powder; S2. Take half of the total amount of the above ultrafine powder, add 1000ml of purified water and 500ml of 45-degree Shaoxing wine, and mix well in a stirrer. S3. Heat to 100℃ and hold for 30 minutes, then let it cool naturally to room temperature for 1 hour; S4. Mix the remaining half of the ultrafine powder with the ultrafine powder mixture after high-temperature treatment, dry it, and then make it into pellets or granules.

[0008] The present invention has the following advantages: 1. The traditional Chinese medicine formula of this invention is based on the principles of dispelling wind, resolving phlegm, relieving spasms, nourishing yin, reducing fire, and calming yang, and embodies the TCM concept of "treating both the symptoms and the root cause".

[0009] 2. Alpinia oxyphylla warms the spleen and kidneys, strengthens qi, and astringes essence; Uncaria rhynchophylla clears heat and calms the liver, relieves wind and stops spasms; Nardostachys chinensis regulates qi and relieves pain, relieves depression and invigorates the spleen; Paeonia lactiflora nourishes blood and astringes yin, softens the liver and relieves pain, and calms liver yang; Achyranthes bidentata tonifies the liver and kidneys, strengthens tendons and bones, removes blood stasis and unblocks meridians, and guides blood downward; Codonopsis pilosula calms the mind; Panax notoginseng removes phlegm and stops cough, invigorates blood and reduces swelling, detoxifies and relieves pain; Panax ginseng tonifies the kidneys and benefits qi, generates fluids and quenches thirst; Cistanche deserticola tonifies kidney yang, benefits essence and blood, and moistens the intestines and promotes bowel movement; Scutellaria baicalensis clears heat and dries dampness, drains fire and detoxifies, and stops bleeding; Buthus martensii relieves wind and stops spasms, unblocks meridians and relieves pain, attacks toxins and dissipates nodules; Sea snake dispels wind and dampness, invigorates blood and unblocks meridians.

[0010] 3. Uncaria rhynchophylla, Paeonia lactiflora, and Buthus martensii work together to calm the liver, extinguish wind, soften tendons, and stop spasms; Achyranthes bidentata, Cistanche deserticola, and Alpinia oxyphylla nourish the liver and kidneys, replenish essence and marrow; Codonopsis pilosula, Gynostemma pentaphyllum, Nardostachys chinensis, and Scutellaria baicalensis calm the mind, relieve depression, resolve phlegm, clear heat, and warm dryness; Codonopsis pilosula and sea snake tonify the kidneys, replenish qi, harmonize the properties of the herbs, and guide them into the meridians.

[0011] 4. This invention formulates prescriptions based on the traditional efficacy of Chinese medicine and the theory of "principal, assistant, adjuvant, and guide," which can not only treat both the root cause and symptoms but also address concurrent symptoms by calming the mind, relieving depression, and resolving phlegm, thereby improving the efficacy for patients in multiple ways.

[0012] 5. This invention has been verified through mouse experiments and clinical trials to have good preventive and therapeutic effects on Parkinson's syndrome. Detailed Implementation

[0013] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions will be clearly and completely described below in conjunction with specific embodiments of the present invention.

[0014] Example 1 A method for preparing a traditional Chinese medicine formula for the prevention and treatment of Parkinson's syndrome includes the following steps: S1. Weigh out 100g of Alpinia oxyphylla, 100g of Uncaria rhynchophylla, 100g of Nardostachys chinensis, 100g of Paeonia lactiflora, 70g of Achyranthes bidentata, 70g of Codonopsis pilosula, 70g of Panax quinquefolius, 70g of Codonopsis pilosula, 70g of Cistanche deserticola, 70g of Scutellaria baicalensis, 40g of Buthus martensii, and 40g of Nelumbo nucifera according to the specified ratio, mix them together and process them into 600-mesh ultrafine powder; S2. Take half of the total amount of the above ultrafine powder, add 1000ml of purified water and 500ml of 45-degree Shaoxing wine, and mix well in a stirrer. S3. Heat to 100℃, maintain at 100℃ for 30 minutes, and then allow it to cool naturally to room temperature for 1 hour; S4. Mix the remaining half of the ultrafine powder with the ultrafine powder mixture after high-temperature treatment, dry it, and then make it into pellets or granules.

[0015] Example 2 A method for preparing a traditional Chinese medicine formula for the prevention and treatment of Parkinson's syndrome includes the following steps: S1. Weigh out 100g of Alpinia oxyphylla, 100g of Uncaria rhynchophylla, 100g of Nardostachys chinensis, 100g of Paeonia lactiflora, 70g of Achyranthes bidentata, 70g of Codonopsis pilosula, 70g of Panax quinquefolius, 70g of Codonopsis pilosula, 70g of Cistanche deserticola, 70g of Scutellaria baicalensis, 40g of Buthus martensii, and 40g of Nelumbo nucifera according to the specified ratio, mix them together and process them into 1000-mesh ultrafine powder; S2. Take half of the total amount of the above ultrafine powder, add 1000ml of purified water and 500ml of 45-degree Shaoxing wine, and mix well in a stirrer. S3. Heat to 100℃, maintain at 100℃ for 30 minutes, and then allow it to cool naturally to room temperature for 1 hour; S4. Mix the remaining half of the ultrafine powder with the ultrafine powder mixture after high-temperature treatment, dry it, and then make it into pellets or granules.

[0016] Conducting a mouse subacute PD model with MPTP-induced spinner behavior experiment Male C57BL / 6 mice, with a body weight of (18.0-22.0) g, were selected as the primary strain to be sensitive to MPTP. Using the formulation prepared in Example 1 as a base, and based on the conversion method for equivalent drug doses between humans and experimental animals (using the body surface area ratio of a standard body weight mouse of 20g and a human of 70kg), the clinical equivalent dose was calculated to be 117 g / kg / day. This was used as the medium dose, with the high and low doses being 2 times and 0.5 times the clinical equivalent dose, respectively. The decoction was prepared using traditional methods, following the principle of decocting the herbs first and then adding them later. The medium-dose group was concentrated to 8.6 g / mL, the high-dose group to 17.2 g / mL, and the low-dose group to 4.3 g / mL, and stored at 4°C for later use.

[0017] Levodopa (specification: levodopa) 200mg: (benserazide) 50mg, based on the clinical maintenance dose and according to the conversion method of equivalent dose between humans and experimental animals (calculated based on the body surface area ratio of a standard body weight mouse of 20g and a human of 70kg), the calculated daily levodopa dose required for mice is 97.5mg / kg. The tablets were ground into powder and dissolved in 0.9% sodium chloride injection to obtain a levodopa solution concentration of 9.75mg / mL, which was stored at 4℃ for later use. Following the modeling method of intraperitoneal injection of 30mg / kg / day, MPTP was dissolved in 0.9% sodium chloride injection according to the administered concentration and dosage, shaken well, and prepared to a concentration of 3mg / mL, which was stored at 4℃ for later use.

[0018] Seventy male C57 / BL6 mice underwent three days of behavioral training and were weighed. They were then randomly divided into a normal control group (n=10) and a model group (n=60). The mice were injected intraperitoneally with MPTP (30 mg / kg) to establish a chronic model, administered every three days for a total of ten times. The normal control group received an equal volume of saline intraperitoneally. Model establishment was assessed after the sixth intraperitoneal injection; 56 out of the 60 mice successfully established the model. Subsequently, another 50 successfully modeled mice were randomly selected and divided into a model group, a levodopa group, and low, medium, and high-dose groups (n=10 per group). These mice were administered the levodopa via gavage after the sixth intraperitoneal injection and continued for 14 days. Model establishment was evaluated after the sixth intraperitoneal injection. The evaluation method is as follows: 0 points are awarded for mice exhibiting similar behavior to normal mice with no symptoms; 1 point is awarded for the presence of piloerection, arched back, and intermittent fine tremors, but with free movement; 2 points are awarded for frequent tremors, slowed movements, tail tremors, and gradually restricted movement; 3 points are awarded for persistent tremors, significantly slowed movements, tail erection, limb stiffness, and significantly restricted movement; 4 points are awarded if the mouse is near death or dies due to generalized paralysis or convulsions. A score of 2-3 indicates successful model establishment.

[0019] Motor function was evaluated on days 0, 6, 12, and 18 after the first gavage. For the rotundus test: Before the formal experiment, mice were placed on a rotundus and trained on a running wheel at a constant speed of 4 r / min for three consecutive days, three times a day with 15-minute intervals. Mice that could not maintain their position on the rotundus for at least 60 seconds were excluded. During the formal experiment, mice were placed on the rotundus and subjected to accelerated movement at a speed increasing from 4 r / min to 40 r / min over 300 seconds. The rotundus automatically recorded the duration of each mouse's movement from the start of the experiment until it fell off the machine.

[0020] Effects of traditional Chinese medicine formula on motor function in PD mice (X±s, n=10) Group normal group Model group Madopa Group low-dose group medium dose group High-dose group 0d, rotor dwell time, s 232.4±8.6 <![CDATA[121.5±17.65 * ]]> <![CDATA[175.6±15.35 # ]]> <![CDATA[134.6±15.74 # ]]> <![CDATA[147.6±17.25 # ]]> <![CDATA[163.7±15.78 # ]]> 6d, rotor dwell time, s 239.7±14.5 <![CDATA[95.84±15.36 * ]]> <![CDATA[192.4±16.56 # ]]> <![CDATA[148.4±17.26 # ]]> <![CDATA[161.4±15.76 # ]]> <![CDATA[179.4±15.36 # ]]> 12d, rotor dwell time, s 246.4±12.5 <![CDATA[86.54±18.35 * ]]> <![CDATA[209.8±15.34 # ]]> <![CDATA[160.8±13.44 # ]]> <![CDATA[174.8±16.74 # ]]> <![CDATA[188.8±18.34 # ]]> 18d, rotor dwell time, s 251.9±15.8 <![CDATA[74.78±16.75 * ]]> <![CDATA[216.5±14.84 # ]]> <![CDATA[175.8±12.45 # ]]> <![CDATA[189.8±14.85 # ]]> <![CDATA[197.2±17.88 # ]]> Note: Compared with the normal group, *P<0.05; compared with the model group, #P<0.05 Results: Compared with the model group, the low, medium and high dose groups all increased the time mice spent on the rotarod, indicating that the traditional Chinese medicine formula was effective in treating subacute PD disease in mice.

[0021] Diagnostic criteria: Western medicine diagnostic criteria: conforms to the "Diagnosis of Parkinson's Disease" issued by the Movement Disorders and PD Group of the Neurology Branch of the Chinese Medical Association in 2006; Traditional Chinese medicine diagnosis refers to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial)" and the "Standards for Diagnosis and Efficacy Evaluation of Tremor Syndrome in the Elderly in Traditional Chinese Medicine (Trial)".

[0022] Clinical data Forty patients with Parkinson's disease (PD) were recruited and randomly divided into a treatment group and a control group using a random number table, with 20 patients in each group. The treatment group consisted of 12 males and 8 females, aged 45-75 years, with a pre-treatment UPDRS score of 57.34±35.67. The control group consisted of 11 males and 9 females, aged 46-74 years, with a pre-treatment UPDRS score of 58.73±27.34.

[0023] control group Administer 1 / 4 tablet of Madopar (250) standard tablet orally, 3 times daily. If the effect is not obvious, the dosage can be gradually increased. Dosage increase method: after 1 week, increase to 1 / 2 tablet each time, 3 times daily; after 2 weeks, increase to 3 / 4 tablet each time, 3 times daily; after 3 weeks, increase to 1 tablet each time, 3 times daily. Maximum dosage: Madopar (250) standard tablet ≤ 3 tablets / day.

[0024] experimental group The pills are made using the traditional Chinese medicine of this invention. Take twice daily, once in the morning and once in the evening, for a course of 28 days.

[0025] The patient was scored using the internationally recognized Unified Parkinson's Disease Rating Scale (UPDRS), and symptoms were assessed once before and once after treatment.

[0026] Clinical efficacy comparison Group Significant improvement improve invalid Overall efficiency control group 2 7 11 45% experimental group 5 9 6 70% Comparison of UPDRS scores before and after treatment between the control group and the experimental group (X±s, points) Group Time Node UPDRS score control group Before treatment 36.58±7.46 After treatment <![CDATA[28.65±6.53 ** ]]> Treatment group Before treatment 37.65±6.58 After treatment <![CDATA[25.87±7.45 ** ]]> Note: Compared with before treatment, *P<0.05, **P<0.01; compared with the control group, #P<0.05.

[0027] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine formula for the prevention and treatment of Parkinson's syndrome, characterized in that: The ingredients, by weight, include 100 parts of Alpinia oxyphylla, 100 parts of Uncaria rhynchophylla, 100 parts of Nardostachys chinensis, 100 parts of Paeonia lactiflora, 70 parts of Achyranthes bidentata, 70 parts of Codonopsis pilosula, 70 parts of Panax quinquefolius, 70 parts of Codonopsis pilosula, 70 parts of Cistanche deserticola, 70g each of Scutellaria baicalensis, 40 parts of scorpion, and 40 parts of sea snake.

2. The method for preparing a traditional Chinese medicine formula for the prevention and treatment of Parkinson's syndrome according to claim 1, characterized in that, Includes the following steps, S1. Weigh out the Chinese medicinal materials according to the specified proportions, mix them together, and process them into 600-1000 mesh ultrafine powder; S2. Take half of the total amount of the above ultrafine powder, add 1000ml of purified water and 500ml of 45-degree Shaoxing wine, and mix well in a stirrer. S3. Heat to 100℃ and hold for 30 minutes, then let it cool naturally to room temperature for 1 hour; S4. Mix the remaining half of the ultrafine powder with the ultrafine powder mixture after high-temperature treatment, dry it, and then make it into pellets or granules.

3. The application of the traditional Chinese medicine formulation according to claim 1 or the traditional Chinese medicine preparation prepared by the preparation method according to claim 2 in the prevention and treatment of Parkinson's syndrome.