A traditional Chinese medicine composition for treating parkinson disease combined with anxiety and a gel preparation thereof

Abstract

This invention discloses a traditional Chinese medicine composition and its gel formulation for treating Parkinson's disease complicated with anxiety. The gel formulation is made from a hydrogel carrier and a traditional Chinese medicine compound composition coated with nanoparticles. The traditional Chinese medicine compound composition comprises: volatile oil inclusion complexes extracted from Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong, and Aucklandia lappa; water extracts of raw dragon bone, raw oyster shell, Scutellaria baicalensis, Cinnamomum cassia, Poria cocos, Pinellia ternata, Arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, Cuscuta chinensis, Cistanche deserticola, Lycopodium clavatum, Gastrodia elata, Bombyx mori, Paeonia lactiflora, Atractylodes macrocephala, and Glycyrrhiza uralensis; and a mixture of water extracts of Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong, and Aucklandia lappa, concentrated into nano-scale freeze-dried powder; and a mixture of nano-scale powders made from Styrax benzoin, borneol, and cinnabar. The traditional Chinese medicine gel formulation of this invention shows significant efficacy in treating Parkinson's disease complicated with anxiety, acting directly on the target, exhibiting targeted sustained-release effects, improving drug bioavailability, requiring a small dosage, and utilizing transdermal absorption, making it convenient and safer to use.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine compound preparation technology, specifically relating to a traditional Chinese medicine composition for treating Parkinson's disease with anxiety, its gel preparation and preparation method, and more specifically to a nanoscale traditional Chinese medicine composition for treating Parkinson's disease with anxiety, its gel preparation and preparation method. Background Technology

[0002] Parkinson's disease (PD) is the second most common neurodegenerative disease after dementia, and it has become a major global public health challenge: in 2021, the number of patients worldwide reached 11.77 million, and the age-standardized incidence rate increased by 220.07% from 1990 to 2021, with the prevalence climbing to 245.73 per 100,000 people.

[0003] The core pathological feature of Parkinson's disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to dysfunction of the basal ganglia circuitry and causing classic motor symptoms such as tremor, rigidity, and bradykinesia, as well as non-motor symptoms such as anxiety, depression, cognitive impairment, and autonomic dysfunction. Anxiety is one of the most common comorbidities of PD, with a prevalence rate as high as 31% to 61%, three times that of the general population, and can occur throughout the entire course of the disease. Anxiety comorbid with Parkinson's disease (PD-A) presents with complex and diverse clinical manifestations, encompassing subtypes such as generalized anxiety, panic disorder, and social phobia. It is often accompanied by symptoms such as depression and apathy, significantly reducing patients' quality of life.

[0004] Traditional treatments for Parkinson's disease primarily target motor dysfunction, neglecting accompanying non-motor symptoms, especially anxiety. Currently, Western medicine mainly treats Parkinson's with anxiety using medications (citalopram, paroxetine, etc.), supplemented by transcranial magnetic stimulation (TMS). However, these methods only improve symptoms to a certain extent and cannot effectively halt disease progression. Long-term use leads to diminished efficacy and a series of complications, placing a heavy burden on society and families. Furthermore, modern Western medical research on this disease largely focuses on the efficacy and side effects of dopamine-choline axis drug therapy, followed by surgical treatments such as stereotactic deep brain stimulation (DBS) and intracranial mass ablation, as well as research in areas such as antioxidant therapy, neuroprotection, and symptomatic treatment.

[0005] The fundamental goal of Parkinson's disease (PD) treatment is to slow disease progression. However, to date, Western medicine has not been very effective in slowing PD progression. Western medicine can only control or partially control symptoms; if medication is used early, the effectiveness of symptom improvement often diminishes in the middle and late stages, becoming less noticeable than before, and may even cause side effects such as on / off phenomena and end-of-dose phenomena. Furthermore, studies show that 30%-80% of Parkinson's patients who have been using levodocin for long-term treatment experience drug-induced motor complications—dyskinesia, such as choreiform, throwing, stereotyped kinesia, and dystonia. This has prompted medical professionals to research and find new drugs and methods for treating the disease. Although amantadine, some antipsychotics such as clozapine, deep brain stimulation (DBS), and intracranial nucleus lesioning can partially address these issues, they have significant side effects or are expensive, and cell transplantation and gene therapy have not yet entered the clinical application stage. Therefore, it is essential to better research and explore the therapeutic potential of traditional Chinese medicine for this disease.

[0006] There are already reports on the use of traditional Chinese medicine compositions for treating Parkinson's disease complicated with anxiety. For example, patent document CN120605299A discloses a traditional Chinese medicine preparation for treating Parkinson's disease and its preparation method, comprising the following raw materials in parts by weight: 20-30 parts of *Chongyangmu*, 17-25 parts of *Duzhong*, 12-16 parts of *Yuantouhao*, 10-15 parts of *Shenjincao*, 8-13 parts of *Yuye*, 7-14 parts of *Chenpi*, 5-10 parts of *Tusizi*, and 2-7 parts of *Gancao*; the preparation can be any one of oral liquid, tablets, pills, granules, or capsules. Patent document CN121221725A discloses a traditional Chinese medicine composition for treating Parkinson's disease, also known as tremor syndrome in Traditional Chinese Medicine, comprising granules made from the following raw materials in the indicated weight ratios: 390g-470g of liver-calming and wind-extinguishing herbs, 140g-160g of Rehmannia glutinosa, 280g-320g of Paeonia lactiflora, 840g-960g of pre-decocted herbs, 390g-450g of blood-activating, qi-regulating, muscle-relaxing, and meridian-clearing herbs, and 305g-355g of detoxifying herbs. Patent document CN121371074A discloses a traditional Chinese medicine composition for treating motor symptoms of Parkinson's disease and its preparation method, made from the following raw materials in the indicated weight ratios: 15-20 parts of Rehmannia glutinosa, 10-15 parts of Eucommia ulmoides, 6-12 parts of Gastrodia elata, 12-18 parts of Haliotis diversicolor, 10-15 parts of Taxillus chinensis, 12-18 parts of Astragalus membranaceus, 6-12 parts of Angelica sinensis, 5-8 parts of Cinnamomum cassia, and 10-15 parts of Paeonia lactiflora. Patent document CN120531838A discloses a traditional Chinese medicine composition for treating early-stage primary Parkinson's disease and its preparation method, comprising the following ingredients: Astragalus membranaceus 2-5 parts by weight, Asparagus cochinchinensis 2-5 parts by weight, Polygonatum odoratum 4-6 parts by weight, Gardenia jasminoides 1-3 parts by weight, fermented soybean 1-3 parts by weight, Trichosanthes kirilowii 2-5 parts by weight, Curcuma longa 1-3 parts by weight, Angelica sinensis 2-5 parts by weight, Ligusticum chuanxiong 1-3 parts by weight, Paeonia lactiflora 5-7 parts by weight, Spatholobus suberectus 2-5 parts by weight, Prunus persica 1-3 parts by weight, Prunus armeniaca 1-3 parts by weight, Cannabis sativa 2-5 parts by weight, Aster tataricus 3-5 parts by weight, Platycodon grandiflorus 1-3 parts by weight, and excipients 15-20 parts by weight. However, existing methods for preparing traditional Chinese medicine compositions involve simple decoction, resulting in poor therapeutic effects.

[0007] With the increasing prominence of my country's aging population, the incidence of Parkinson's disease continues to rise. Parkinson's patients not only experience impaired motor function but also suffer from psychological and emotional problems such as anxiety and depression. Anxiety often manifests as worry about the future, fear of disease progression, and unease about daily activities. Anxiety symptoms not only affect patients' quality of life but may also exacerbate the severity and progression of motor symptoms. Therefore, effectively managing anxiety symptoms is crucial for the overall treatment of Parkinson's patients. There is an urgent need to explore and develop effective and safe traditional Chinese medicine preparations for treating Parkinson's disease, especially for Parkinson's disease complicated by anxiety, which can significantly improve patients' quality of life and has significant practical implications.

[0008] The treatment of Parkinson's disease combined with anxiety has not yet achieved satisfactory results. The limitations of drug treatment, the decline in efficacy in the middle and late stages, adverse reactions such as dizziness, headache, drowsiness, liver and kidney damage, and hallucinations, as well as the lack of standardized treatment methods are all challenges that need to be addressed. Summary of the Invention

[0009] This invention provides a traditional Chinese medicine composition for treating Parkinson's disease with anxiety, its gel formulation, and a preparation method thereof, comprising a gel and a nanoscale traditional Chinese medicine compound composition loaded in the gel.

[0010] To achieve the above objectives, the technical solution of the present invention is as follows.

[0011] This invention discloses a traditional Chinese medicine composition for treating Parkinson's disease complicated with anxiety, comprising: Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong, Aucklandia lappa, raw dragon bone, raw oyster shell, Scutellaria baicalensis, Cinnamomum cassia, Poria cocos, Pinellia ternata, Arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, Cuscuta chinensis, Cistanche deserticola, Lycopodium clavatum, Gastrodia elata, Bombyx mori, Paeonia lactiflora, Atractylodes macrocephala, prepared licorice root, Styrax benzoin, borneol, and cinnabar, in a mass ratio of (3-4):(3-4):(3-4):(3-4):(1) 0~20): (10~20): (2~4): (2~5): (4~20): (2~4): (3~4): (1~3): (1~4): (1~3): (3~10): (3~7): (3~7): (3~5): (3~4): (1~4): (3~10): (3~6): (2~3): (1~3): (0.6~2): (0.03~0.1). For example, the above-mentioned Chinese herbal medicine composition is formulated as follows: Bupleurum chinense 9-12 parts, Cyperus rotundus 9-12 parts, Ligusticum chuanxiong 9-12 parts, Aucklandia lappa 9-12 parts, raw dragon bone 30-60 parts, raw oyster shell 30-60 parts, Scutellaria baicalensis 6-12 parts, Cinnamomum cassia 6-15 parts, Poria cocos 12-60 parts, Pinellia ternata 6-12 parts, Arisaema cum bile 9-12 parts, dried ginger 3-9 parts, ginseng 3-12 parts, rhubarb 3-9 parts, gypsum 9-30 parts, Cuscuta chinensis 9-20 parts, Cistanche deserticola 9-20 parts, Lycopodium clavatum 9-15 parts, Gastrodia elata 9-12 parts, Bombyx mori 3-10 parts, Paeonia lactiflora 9-30 parts, Atractylodes macrocephala 9-18 parts, prepared licorice root 6-9 parts, Styrax benzoin 3-9 parts, borneol 2-6 parts, and cinnabar 0.1-0.3 parts.

[0012] Preferably, the traditional Chinese medicine composition for treating Parkinson's disease complicated with anxiety according to the present invention is formulated as follows: Bupleurum chinense 10 parts, Cyperus rotundus 10 parts, Ligusticum chuanxiong 10 parts, Aucklandia lappa 10 parts, raw dragon bone 45 parts, raw oyster shell 45 parts, Scutellaria baicalensis 9 parts, Cinnamomum cassia 12 parts, Poria cocos 30 parts, Pinellia ternata 9 parts, Arisaema cum bile 10 parts, dried ginger 8 parts, ginseng 10 parts, rhubarb 6 parts, gypsum 15 parts, Cuscuta chinensis 18 parts, Cistanche deserticola 18 parts, Lycopodium clavatum 12 parts, Gastrodia elata 10 parts, Bombyx mori 6 parts, Paeonia lactiflora 15 parts, Atractylodes macrocephala 12 parts, prepared licorice root 7 parts, Styrax benzoin 6 parts, borneol 5 parts, and cinnabar 0.15 parts.

[0013] The above-mentioned traditional Chinese medicine composition, with its rationally combined principal, assistant, and adjuvant herbs, was used solely for water decoction or wine decoction extraction to treat Parkinson's disease complicated by anxiety. Trial use on patients demonstrated its ability to effectively slow the progression of Parkinson's disease. While the water decoction of the above-mentioned traditional Chinese medicine composition showed some efficacy, the effect was not outstanding and did not achieve the desired results.

[0014] Therefore, this invention breaks through the traditional Chinese medicine preparation process and creatively uses the above-mentioned Chinese medicine composition for treating Parkinson's disease with anxiety to make a Chinese medicine gel preparation. Clinical trials show that the Chinese medicine gel preparation of this invention can effectively reduce anxiety symptoms, improve patients' cognitive function and quality of life, and improve patients' mood.

[0015] This invention discloses a traditional Chinese medicine gel preparation for treating Parkinson's disease complicated with anxiety, comprising a hydrogel carrier in a volume ratio of (60-95):(5-40) and a traditional Chinese medicine compound composition coated with nanoparticles loaded in the hydrogel carrier; wherein the hydrogel carrier is acellular bladder matrix (BAM); and the nanoparticle-coated traditional Chinese medicine compound composition is a traditional Chinese medicine compound composition extracted using the traditional Chinese medicine composition for treating Parkinson's disease complicated with anxiety, and then coated in nanoscale mesoporous polydopamine (mPDA); the traditional Chinese medicine compound composition... This refers to: a mixture of volatile oil inclusion complexes extracted from Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong, and Aucklandia lappa; water extracts of raw dragon bone, raw oyster shell, Scutellaria baicalensis, Cinnamomum cassia, Poria cocos, Pinellia ternata, Arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, Cuscuta chinensis, Cistanche deserticola, Lycopodium clavatum, Gastrodia elata, Bombyx mori, Paeonia lactiflora, Atractylodes macrocephala, and Glycyrrhiza uralensis; and a mixture of water extracts of Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong, and Aucklandia lappa, prepared into nano-scale freeze-dried powder; and a mixture of nano-scale powders made by grinding Styrax benzoin, borneol, and cinnabar; wherein the mass ratio of the traditional Chinese medicine compound composition to mesoporous polydopamine is (50-100):1.

[0016] The bladder acellular matrix (BAM) is a natural component of the bladder, consisting of the extracellular matrix remaining after decellularization to remove cellular components containing cell antigens. BAM can be a commercially available product or the whole bladder acellular matrix (BAM) prepared using the perfusion acellular system disclosed in the reference [Xiao Shuwei, Fu Weijun, Wang Pengchao, et al. Study on the preparation of whole bladder acellular matrix using perfusion acellular system and its combination with adipose stem cells to construct tissue-engineered bladder [J]. Chinese Journal of Urology, 2023, Vol. 44, No. 3]. Preferably, BAM is prepared from fresh porcine bladder tissue. The hydrogel made from the bladder acellular matrix (BAM) contains elastic fibers and a collagen mesh scaffold, significantly reducing immunogenicity and making it less likely to induce immune rejection in the host. It is also soft, easily moldable, does not break, and does not shrink upon contact with water, making it convenient to use and suitable as a good drug carrier. Furthermore, as an extracellular matrix, it exhibits good biocompatibility and can induce tissue regeneration.

[0017] The mesoporous polydopamine (mPDA) is a mesoporous nanoparticle of a melanin-like polymer, with a particle size of 100–200 nm and a mesopore size of 2–50 nm; for example, Xianfeng Nano's 104785, with a specification of 1 mg / ml. The mPDA structure contains a large number of amino groups and o-phenylenediol groups, allowing for surface modification. Compared with other nanocarriers, mPDA exhibits excellent biocompatibility and biodegradability, pH response at low pH values, excellent adhesion, ease of surface modification, high near-infrared light absorption, and high photothermal conversion efficiency. Due to its mesoporous structure and large surface area, mPDA has a high loading capacity, making it an ideal carrier.

[0018] The present invention discloses a method for preparing a traditional Chinese medicine gel preparation for treating Parkinson's disease complicated with anxiety, comprising the following steps: S1, volatile oils are extracted from Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong and Aucklandia lappa using steam distillation, and the decoction is collected as the first aqueous extract; the volatile oils are then encapsulated with β-cyclodextrin to obtain volatile oil inclusion complexes; S2, raw dragon bone, raw oyster shell, scutellaria baicalensis, cinnamon twig, poria cocos, pinellia ternata, arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, cuscuta chinensis, cistanche deserticola, lycopodium clavatum, gastrodia elata, silkworm pupae, white peony root, atractylodes macrocephala, and prepared licorice root are decocted in water to collect the second aqueous extract; the second and first aqueous extracts are combined and the water is removed to obtain the third aqueous extract; the third aqueous extract is atomized into small droplets using ultrasonic spraying technology and then rapidly sent into liquid ammonia for pre-solidification; then it is transferred to a temperature of -60~5℃ and a pressure of 1.25~1.5KPa for freeze drying to obtain solidified microparticles; the solidified microparticles are ball-milled to obtain nano-sized freeze-dried powder of traditional Chinese medicine compound extract, which is then sterilized by ultraviolet irradiation; S3, Styrax, borneol and cinnabar are poured into a grinder and sheared and crushed to obtain preliminary powder; the preliminary powder is passed through a 100-mesh sieve and then ultra-finely crushed to below 50nm to obtain nano-sized powder of Styrax, borneol and cinnabar, which is then sterilized by ultraviolet irradiation. S4, the volatile oil inclusion complex, the freeze-dried powder of the traditional Chinese medicine compound extract, and the nano-sized powders of styrax, borneol, and cinnabar are mixed to obtain the traditional Chinese medicine compound composition; S5, disperse mesoporous polydopamine (mPDA) in water, add the traditional Chinese medicine compound composition, and stir continuously at room temperature for at least 10 hours; after centrifugation and washing, collect the precipitate to obtain the nanoparticle-coated traditional Chinese medicine compound composition; S6. Mix the aqueous solution of decellularized bladder matrix (BAM) and the nanoparticle-coated traditional Chinese medicine compound composition at a volume ratio of (60-95):(5-40), and stir at room temperature to form a gel, thereby obtaining the traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety.

[0019] Preferably, in step S1, the mass ratio of the total mass of Bupleurum, Cyperus, Ligusticum and Aucklandia to water is 1:(10-20); the extraction time by steam distillation is not less than 6 hours; more preferably, the mass ratio of the total mass of Bupleurum, Cyperus, Ligusticum and Aucklandia to water is 1:(14-16); the extraction time by steam distillation is 7-9 hours.

[0020] Preferably, in step S1, when the volatile oil is encapsulated by β-cyclodextrin, the amount of β-cyclodextrin used is 2 to 5 times the mass of the volatile oil; more preferably, the amount of β-cyclodextrin used is 3 to 4 times the mass of the volatile oil.

[0021] Preferably, in step S2, the total mass ratio of raw dragon bone, raw oyster shell, scutellaria baicalensis, cinnamon twig, poria cocos, pinellia ternata, arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, cuscuta chinensis, cistanche deserticola, lycopodium clavatum, gastrodia elata, silkworm pupae, white peony root, atractylodes macrocephala, and prepared licorice root to water is 1:(6-10), and the decoction time is 1-3 hours; the number of decoctions includes 1-3 times.

[0022] Preferably, in step S2, after the second and first aqueous extracts are combined, water is removed by alcohol precipitation and / or vacuum drying. The alcohol precipitation concentration is performed for less than 6 hours at a temperature below 70°C, concentrating the aqueous extract to a relative density of 1.10–1.14 g / ml; the working volume concentration of ethanol used in the alcohol precipitation concentration is approximately 70%; and the vacuum drying temperature is below 80°C.

[0023] Preferably, in steps S2 and S3, the grinding balls used for ball milling are zirconia balls, the ball milling temperature is 25-35℃, and the ball milling time is 3-5 hours; deionized water is used to cool the ball mill jar during the grinding process.

[0024] Preferably, in step S3, the pre-curing process parameters are: ultrasonic power of 2.5-3.5W, flow rate of the third water extract of 4-8mL / min, and pre-curing time of 6-8min.

[0025] Preferably, in step S3, the freeze-drying process is as follows: drying at -40 to -35°C for 24 to 32 hours, drying at -30 to -25°C for 2 to 3 hours, drying at -25 to -15°C for 1 to 3 hours, drying at -10 to -5°C for 1 to 3 hours, and drying at 0 to 5°C for 1 to 2 hours.

[0026] Preferably, in step S5, the mass concentration of the mesoporous polydopamine (mPDA) dispersed in water is 0.005–0.02 mg / ml.

[0027] Preferably, in step S6, when calculating the ratio of the aqueous solution of the decellularized bladder matrix to the nanoparticle-coated traditional Chinese medicine compound composition, the mass concentration of the decellularized bladder matrix is ​​based on 6 mg / ml.

[0028] This invention also provides the application of the traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety in the preparation of drugs for treating Parkinson's disease with anxiety; the traditional Chinese medicine gel preparation can be absorbed directly into the brain orifices through transdermal absorption via acupoints such as the temples and Yingxiang acupoints, and through nasal absorption, and has a sustained-release effect. It can also be made into a gel patch for transdermal absorption, which is convenient, safe and efficient to use.

[0029] This invention uses mesoporous polydopamine (mPDA) to coat a traditional Chinese medicine compound composition and load it into a bladder decellularized matrix (BAM) gel drug delivery system, which has the following advantages: The BAM and mPDA used in this invention are excellent drug delivery systems. By utilizing the cross-linking effects between ionic cross-links, non-covalent bonds and amide bonds, as well as the π-π stacking interaction between the PDA structure and the π-electron-rich TMB molecules, nanoscale traditional Chinese medicine compound extracts are successfully loaded into Gel@BAM@mPDA to obtain a gel formulation of traditional Chinese medicine compound extracts.

[0030] (1) To achieve sustained or controlled release of drugs. Gel-based controlled-release systems refer to systems that simply prolong the drug release time and automatically release the drug at a predetermined rate within a predetermined time. Some drugs with short half-lives require repeated daily administration, which may affect efficacy due to poor patient compliance or unintentional missed doses. Sustained or controlled release of drugs can be achieved by using technologies such as natural gels as carriers.

[0031] (2) Improve the bioavailability of drugs and conserve Chinese medicinal resources. By preparing drugs into nano-sized lyophilized powder and loading them into gels, they can act directly on the target and have a targeted sustained-release effect, thereby improving the bioavailability of drugs, reducing the amount of drugs used, alleviating the unlimited exploitation of limited Chinese medicinal resources, and thus playing a role in protecting the species and realizing the sustainable development and protection of Chinese medicinal resources.

[0032] (3) Enhance the original effects of traditional Chinese medicine compound compositions and generate new efficacy. The large specific surface area and small size effect of traditional Chinese medicine compound extracts will increase the solubility and dissolution rate of the drug, thereby increasing the bioavailability of the drug, accelerating the onset time of the drug, and enhancing the efficacy of the original drug. In this invention, after the traditional Chinese medicine composition is coated in mPDA and then loaded into BAM gel drug delivery system, it can be directly applied to the target tissue through external treatment methods such as nasal absorption and epidermal application. Compared with the original drug, the physicochemical properties, biological activity and pharmacological effects of this nanoscale traditional Chinese medicine compound composition composite gel preparation have changed, and even generated new efficacy, expanding the scope of treatment.

[0033] (4) Enhancing ease of use is conducive to the standardization and internationalization of traditional Chinese medicine. Traditional Chinese medicine and its dosage forms are limited, the processing technology is cumbersome and outdated, the quality standards are poorly controllable, and the international market share is very small. Introducing nanogel technology into the research and development of traditional Chinese medicine preparations is conducive to the standardization and normalization of traditional Chinese medicine preparations. Establishing a series of patented technologies and innovative methods with independent intellectual property rights in the preparation technology, pharmacodynamics, and toxicology of nanogel traditional Chinese medicine will enhance the market competitiveness of traditional Chinese medicine in my country and promote the modernization of traditional Chinese medicine. Detailed Implementation

[0034] The specific embodiments of the present invention will be further described below. It should be noted that these descriptions are for the purpose of aiding understanding the present invention, but do not constitute a limitation thereof. Furthermore, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0035] Example 1 A traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety is made using a hydrogel carrier with a volume ratio of 70:30 and a traditional Chinese medicine compound composition coated with nanoparticles loaded in the hydrogel carrier. The hydrogel carrier is acellular bladder matrix (BAM). The nanoparticle-coated traditional Chinese medicine compound composition is a traditional Chinese medicine compound composition extracted from a traditional Chinese medicine composition for treating Parkinson's disease with anxiety, and then coated in nanoscale mesoporous polydopamine (mPDA). The traditional Chinese medicine compound composition consists of: volatile oil inclusion complexes extracted from 10 parts of Bupleurum chinense, 10 parts of Cyperus rotundus, 10 parts of Ligusticum chuanxiong, and 10 parts of Aucklandia lappa, and their aqueous solutions. The extracts consist of 45 parts raw dragon bone, 45 parts raw oyster shell, 9 parts Scutellaria baicalensis, 12 parts cinnamon twig, 30 parts Poria cocos, 9 parts Pinellia ternata, 10 parts Arisaema cum Bile, 8 parts dried ginger, 10 parts ginseng, 6 parts rhubarb, 15 parts gypsum, 18 parts Cuscuta chinensis, 18 parts Cistanche deserticola, 12 parts Lycopodium clavatum, 10 parts Gastrodia elata, 6 parts Bombyx mori, 15 parts Paeonia lactiflora, 12 parts Atractylodes macrocephala, and 7 parts prepared licorice root. A mixture of the two water extracts was concentrated to prepare a nano-scale freeze-dried powder. A mixture of 6 parts Styrax benzoin, 5 parts borneol, and 0.15 parts cinnabar was ground into a nano-scale powder. The mass ratio of the traditional Chinese medicine compound composition to mesoporous polydopamine was 70:1. The preparation method of a traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety includes the following steps: S1, Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong and Aucklandia lappa were soaked in water at a total mass ratio of 1:15 to water, and the volatile oil was extracted by steam distillation for 8 hours; at the same time, their decoction was collected as the first water extract; the volatile oil was encapsulated with 4 times its mass of β-cyclodextrin to obtain volatile oil inclusion complexes with a particle size of 10-50 nm. S2, raw dragon bone, raw oyster shell, scutellaria baicalensis, cinnamon twig, poria cocos, pinellia ternata, arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, cuscuta chinensis, cistanche deserticola, lycopodium clavatum, gastrodia elata, silkworm pupae, white peony root, atractylodes macrocephala, and prepared licorice root were decocted in water at a ratio of 1:8. The decoction was performed three times, with each decoction lasting 2 hours. The decoctions from the three decoctions were collected as the second aqueous extract. The second aqueous extract and the first aqueous extract were combined and concentrated at 65°C for 5 hours using alcohol precipitation. The water was then removed by vacuum drying to obtain an extract with a relative density of 1.12 g / ml, which was used as the third aqueous extract. Ultrasonic spraying technology was used with an ultrasonic power of 3.0W and a flow rate of 6.5mL / min for the third aqueous extract. The extract was atomized into small droplets and rapidly fed into liquid ammonia for pre-curing for 7 minutes. The extract was then transferred to a freeze dryer and dried at 1.35 kPa under the following conditions: -40 to -35°C for 28 hours, -30 to -25°C for 2 hours, -25 to -15°C for 2 hours, -10 to -5°C for 2 hours, and 0 to 5°C for 2 hours, to obtain solidified microparticles. These solidified microparticles were then ball-milled to a particle size of 10–50 nm to obtain nanoscale freeze-dried powder of the traditional Chinese medicine compound extract, which was then sterilized by ultraviolet irradiation. S3, Styrax, borneol and cinnabar are poured into a grinder and sheared and crushed to obtain preliminary powder; the preliminary powder is passed through a 100-mesh sieve and then ultra-finely crushed to below 50nm to obtain nano-sized powder of Styrax, borneol and cinnabar, which is then sterilized by ultraviolet irradiation. S4, volatile oil inclusion complex, freeze-dried powder of traditional Chinese medicine compound extract, and nano-sized powders of styrax, borneol and cinnabar are mixed to obtain traditional Chinese medicine compound composition; S5, mesoporous polydopamine (mPDA) nanoparticles were dispersed in an aqueous solvent (mass concentration of dispersion was 0.01 mg / ml), and the traditional Chinese medicine compound composition was added at a mass ratio of 70:1 to mPDA. The mixture was stirred continuously at room temperature for 14 h. After the reaction was completed, the mixture was centrifuged, washed, and the precipitate was collected to obtain the nanoparticle-coated traditional Chinese medicine compound composition.

[0036] S6. A BAM aqueous solution (BAM mass concentration of 6 mg / ml) and a traditional Chinese medicine compound composition coated with nanoparticles are mixed at a volume ratio of 70:30. The mixture is stirred at 25°C with a magnetic stirrer at a speed of 150 r / min for 8 min to form a gel, thus obtaining the final traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety.

[0037] Example 2 A traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety is made using a hydrogel carrier with a volume ratio of 80:20 and a traditional Chinese medicine compound composition coated with nanoparticles loaded in the hydrogel carrier. The hydrogel carrier is acellular bladder matrix (BAM). The nanoparticle-coated traditional Chinese medicine compound composition is a traditional Chinese medicine compound composition extracted from a traditional Chinese medicine composition for treating Parkinson's disease with anxiety, and then coated in nanoscale mesoporous polydopamine (mPDA). The traditional Chinese medicine compound composition consists of volatile oil inclusion complexes extracted from 12 parts of Bupleurum chinense, 12 parts of Cyperus rotundus, 12 parts of Ligusticum chuanxiong, and 12 parts of Aucklandia lappa, and their water extracts. The ingredients included: 60 parts raw dragon bone, 60 parts raw oyster shell, 12 parts Scutellaria baicalensis, 15 parts cinnamon twig, 55 parts Poria cocos, 12 parts Pinellia ternata, 12 parts Arisaema cum Bile, 9 parts dried ginger, 12 parts ginseng, 9 parts rhubarb, 30 parts gypsum, 20 parts Cuscuta chinensis, 20 parts Cistanche deserticola, 15 parts Lycopodium clavatum, 12 parts Gastrodia elata, 10 parts Bombyx mori, 18 parts Paeonia lactiflora, 18 parts Atractylodes macrocephala, and 9 parts prepared licorice root; a mixture of the two water extracts was concentrated to prepare a nano-scale freeze-dried powder; and a mixture of 9 parts Styrax benzoin, 6 parts borneol, and 0.2 parts cinnabar were ground into nano-scale powder; the mass ratio of the traditional Chinese medicine compound composition to mesoporous polydopamine was 80:1. The preparation method of a traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety includes the following steps: S1, Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong and Aucklandia lappa were soaked in water at a total mass ratio of 1:18 to water, and the volatile oil was extracted by steam distillation for 9 hours; at the same time, their decoction was collected as the first water extract; the volatile oil was encapsulated with 4 times its mass of β-cyclodextrin to obtain volatile oil inclusion complexes with a particle size of 10-50 nm. S2, raw dragon bone, raw oyster shell, scutellaria baicalensis, cinnamon twig, poria cocos, pinellia ternata, arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, cuscuta chinensis, cistanche deserticola, lycopodium clavatum, gastrodia elata, silkworm pupae, white peony root, atractylodes macrocephala, and prepared licorice root were decocted in water at a ratio of 1:6. The decoction was performed three times, with each decoction lasting 2.5 hours. The decoctions from the three decoctions were collected as the second aqueous extract. The second aqueous extract and the first aqueous extract were combined and concentrated at 65°C for 5 hours using alcohol precipitation. The water was then removed by vacuum drying, and the extract with a relative density of 1.14 g / ml was obtained as the third aqueous extract. Ultrasonic spraying technology was used with an ultrasonic power of 3.5W and a flow rate of 8mL / min for the third aqueous extract. The third aqueous extract was atomized into small droplets and then rapidly fed into liquid ammonia for pre-curing for 7 minutes. The extract was then transferred to a freeze dryer and dried at 1.35 kPa at -40 to -35°C for 26 hours, -30 to -25°C for 3 hours, -25 to -15°C for 2 hours, -10 to -5°C for 2 hours, and 0 to 5°C for 2 hours to obtain solidified microparticles. These solidified microparticles were then ball-milled to a particle size of 10–50 nm to obtain nanoscale freeze-dried powder of the traditional Chinese medicine compound extract, which was then sterilized by ultraviolet irradiation. S3, Styrax, borneol and cinnabar are poured into a grinder and sheared and crushed to obtain preliminary powder; the preliminary powder is passed through a 100-mesh sieve and then ultra-finely crushed to below 50nm to obtain nano-sized powder of Styrax, borneol and cinnabar, which is then sterilized by ultraviolet irradiation. S4, volatile oil inclusion complex, freeze-dried powder of traditional Chinese medicine compound extract, and nano-sized powders of styrax, borneol and cinnabar are mixed to obtain traditional Chinese medicine compound composition; S5. Mesoporous polydopamine (mPDA) nanoparticles were dispersed in an aqueous solvent (mass concentration of dispersion was 0.015 mg / ml). The traditional Chinese medicine compound composition was added at a mass ratio of 80:1 to mPDA. The mixture was stirred continuously at room temperature for 15 h. After the reaction was completed, the mixture was centrifuged, washed, and the precipitate was collected to obtain the nanoparticle-coated traditional Chinese medicine compound composition.

[0038] S6. A BAM aqueous solution (BAM concentration of 6 mg / ml) and a traditional Chinese medicine compound composition coated with nanoparticles are mixed at a volume ratio of 80:20. The mixture is stirred at 25°C with a magnetic stirrer at 150 r / min for 8 min to form a gel, thus obtaining the final traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety.

[0039] Example 3 A traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety is made using a hydrogel carrier with a volume ratio of 60:40 and a traditional Chinese medicine compound composition coated with nanoparticles loaded on the hydrogel carrier. The hydrogel carrier is acellular bladder matrix (BAM). The nanoparticle-coated traditional Chinese medicine compound composition is a traditional Chinese medicine compound composition extracted from a traditional Chinese medicine composition for treating Parkinson's disease with anxiety, and then coated in nanoscale mesoporous polydopamine (mPDA). The traditional Chinese medicine compound composition consists of: volatile oil inclusion complexes extracted from 9 parts of Bupleurum chinense, 9 parts of Cyperus rotundus, 9 parts of Ligusticum chuanxiong, and 9 parts of Aucklandia lappa. The water extracts of these ingredients, including 30 parts raw dragon bone, 30 parts raw oyster shell, 6 parts Scutellaria baicalensis, 6 parts cinnamon twig, 12 parts Poria cocos, 6 parts Pinellia ternata, 9 parts Arisaema cum Bile, 3 parts dried ginger, 3 parts ginseng, 3 parts rhubarb, 9 parts gypsum, 9 parts Cuscuta chinensis, 9 parts Cistanche deserticola, 9 parts Lycopodium clavatum, 9 parts Gastrodia elata, 3 parts Bombyx mori, 9 parts Paeonia lactiflora, 9 parts Atractylodes macrocephala, and 6 parts prepared licorice root, were concentrated into nano-scale freeze-dried powder, and a mixture of 3 parts Styrax benzoin, 2 parts borneol, and 0.1 parts cinnabar were ground into nano-scale powder; the mass ratio of the traditional Chinese medicine compound composition to mesoporous polydopamine was 50:1. The preparation method of a traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety includes the following steps: S1, Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong and Aucklandia lappa were soaked in water at a total mass ratio of 1:10 and the volatile oil was extracted by steam distillation for 6.5 hours; at the same time, their decoction was collected as the first water extract; the volatile oil was encapsulated with 3 times its mass of β-cyclodextrin to obtain volatile oil inclusion complexes with a particle size of 10-50 nm. S2, raw dragon bone, raw oyster shell, scutellaria baicalensis, cinnamon twig, poria cocos, pinellia ternata, arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, cuscuta chinensis, cistanche deserticola, lycopodium clavatum, gastrodia elata, silkworm pupae, white peony root, atractylodes macrocephala, and prepared licorice root were decocted in water at a ratio of 1:10 between the total mass of the Chinese herbs and water. The decoction was performed three times, with each decoction lasting 1.5 hours. The decoction liquids from the three decoctions were collected as the second water extract. The second water extract and the first water extract were combined and concentrated at 65°C for 5 hours using alcohol precipitation. The water was then removed by vacuum drying to obtain an extract with a relative density of 1.10 g / ml, which was used as the third water extract. Ultrasonic spraying technology was used with an ultrasonic power of 2.5W and a flow rate of 5mL / min for the third aqueous extract. The third aqueous extract was atomized into small droplets and then rapidly fed into liquid ammonia for pre-curing for 6 minutes. The extract was then transferred to a freeze dryer and dried at 1.35 kPa under the following conditions: -40 to -35°C for 30 hours, -30 to -25°C for 2 hours, -25 to -15°C for 2 hours, -10 to -5°C for 2 hours, and 0 to 5°C for 2 hours, to obtain solidified microparticles. These solidified microparticles were then ball-milled to a particle size of 10–50 nm to obtain nanoscale freeze-dried powder of the traditional Chinese medicine compound extract, which was then sterilized by ultraviolet irradiation. S3, Styrax, borneol and cinnabar are poured into a grinder and sheared and crushed to obtain preliminary powder; the preliminary powder is passed through a 100-mesh sieve and then ultra-finely crushed to below 50nm to obtain nano-sized powder of Styrax, borneol and cinnabar, which is then sterilized by ultraviolet irradiation. S4, volatile oil inclusion complex, freeze-dried powder of traditional Chinese medicine compound extract, and nano-sized powders of styrax, borneol and cinnabar are mixed to obtain traditional Chinese medicine compound composition; S5, mesoporous polydopamine (mPDA) nanoparticles were dispersed in an aqueous solvent (mass concentration of dispersion was 0.01 mg / ml), and the traditional Chinese medicine compound composition was added at a mass ratio of 50:1 to mPDA. The mixture was stirred continuously at room temperature for 15 h. After the reaction was completed, the mixture was centrifuged, washed, and the precipitate was collected to obtain the nanoparticle-coated traditional Chinese medicine compound composition.

[0040] S6. A BAM aqueous solution (BAM mass concentration of 6 mg / ml) and a traditional Chinese medicine compound composition coated with nanoparticles are mixed at a volume ratio of 60:40. The mixture is stirred at 25°C with a magnetic stirrer at a speed of 150 r / min for 10 min to form a gel, thus obtaining the final traditional Chinese medicine gel preparation for treating Parkinson's disease with anxiety.

[0041] clinical trials 1. General Information: A retrospective analysis was conducted on 120 patients with Parkinson's disease and anxiety admitted to Shanghai Municipal Hospital of Traditional Chinese Medicine from December 2024 to December 2025. They were randomly divided into a control group (n=30), a study group 1 (n=30), a study group 2 (n=30), and a study group 3 (n=30) using a random number table.

[0042] 2. Inclusion and exclusion criteria: (1) Inclusion criteria: those who have been previously diagnosed with Parkinson's disease and have shown anxiety symptoms before the start of the study; The duration of Parkinson's disease medication treatment was ≥30 days, the patient's medication regimen remained relatively stable, and there were no significant adjustments to the medication during the treatment period; the family members agreed to participate in this study and signed an informed consent form.

[0043] (2) Exclusion criteria: history of craniocerebral surgery or impaired consciousness; serious diseases of other systems, such as malignant tumors or organ failure; patients with severe cognitive impairment, such as dementia or severe mental disorders, who are unable to cooperate with the research process.

[0044] 3. Method: (1) All patients in the control group received levodopa tablets (Shanghai Xinyi Wanxiang Pharmaceutical Co., Ltd., National Drug Approval Number H31020888, specification 0.25g) and pramipexole hydrochloride tablets (Zhejiang Jingxin Pharmaceutical Co., Ltd., National Drug Approval Number H20183368, specification 1.0mg). The initial dose of levodopa tablets was 1 tablet / time, 2-3 times / day. After 3-7 days, the dose was increased by 0.5-3.0 tablets each time to achieve the optimal treatment state for Parkinson's disease. The maximum daily dose was <24 tablets, which could be divided into 6 doses per day. The initial dose of pramipexole hydrochloride tablets was 1.5 tablets / time. Subsequently, the dose was gradually increased every 7 days according to the patient's specific symptoms, with an increase of 3 tablets each time, aiming for a maximum dose of <1.5mg / day. If adverse reactions occurred during the medication increase period, the dose increase should be stopped in time, and the dose should be increased again after the adverse symptoms disappeared to ensure the patient's safety and comfort.

[0045] (2) Patients in study group 1 received oral levodopa tablets combined with topical application of the gel preparation of Example 1. The method and dosage of levodopa tablets were the same as those in the control group. The traditional Chinese medicine gel preparation of the present invention was applied to the bilateral temples, bilateral Yingxiang acupoints, and Shenque acupoints, 1 ml per acupoint each time, massaged for 1 minute, 4 times a day, for 2 consecutive months.

[0046] (3) Patients in study group 2 received oral levodopa tablets combined with topical application of the gel preparation of Example 2. The method and dosage of levodopa tablets were the same as those in the control group. The traditional Chinese medicine gel preparation of the present invention was applied to the bilateral temples, bilateral Yingxiang acupoints, and Shenque acupoints. 1 ml was applied to each acupoint each time, massaged for 1 minute, 4 times a day, for 2 consecutive months.

[0047] (4) Patients in the study group 3 received oral levodopa tablets combined with topical application of the gel preparation of Example 3. The method and dosage of levodopa tablets were the same as those in the control group. The traditional Chinese medicine gel preparation of the present invention was applied to the bilateral temples, bilateral Yingxiang acupoints, and Shenque acupoints. 1 ml was applied to each acupoint each time, massaged for 1 minute, 4 times a day, for 2 consecutive months.

[0048] 4. Observation indicators: The Webster symptom score was used to assess treatment effectiveness. The scoring system includes tremor, muscle tone, gait, and postural stability. Treatment efficacy was categorized as markedly effective, effective, or ineffective. Markedly effective indicated a very significant improvement in symptoms; effective indicated a good improvement or some degree of symptom relief; and ineffective indicated no improvement or no symptom relief. The overall effective rate was calculated by combining all scores. The total effective rate was the sum of the number of markedly effective and effective cases.

[0049] The Mini-Mental State Examination (MMSE) was used to assess cognitive function, with a score range of 0 to 30. The MMSE covers aspects such as memory, attention, and orientation. Higher scores indicate better cognitive function.

[0050] The Generic Quality of Life Inventory (GQOIL) was used to assess quality of life, including physical health, mental health, social support, work and family life, to understand an individual's life satisfaction and quality in each area. The scores were directly proportional to the quality of life.

[0051] The Hamilton Anxiety Scale (HAMA) was used to assess changes in patients' anxiety. The scale contains 14 items that cover multiple aspects of anxiety symptoms, including psychological anxiety, physical anxiety, physiological symptoms of anxiety, anxious thoughts and behaviors, etc. The total score ranges from 0 to 56 points, with higher scores indicating more severe anxiety.

[0052] Statistical methods employed SPSS 25.0 statistical analysis software. Normally distributed measurement data (including MMSE, GQOIL, and HAMA scores) were analyzed using (…). The mean ± standard deviation (±s) indicates the statistical significance of data. If the data satisfy homogeneity of variance and regression slope, one-way ANOVA (Antibody-Nonvariate Analysis) is used, and post-hoc pairwise comparisons (HAMA scores) are performed using the Bonferroni method. If the conditions are not met, one-way ANOVA (Antibody-Nonvariate Analysis) is used to analyze the difference in scores before and after treatment, and post-hoc pairwise comparisons (MMSE, GQOIL scores) are performed using the Tukey method. Paired t-tests are used for within-group comparisons. Count data (including treatment effect) are expressed as [cases (%)], and the Kruskal-Wallis H test is used. The significance level is set at α=0.05, and P<0.05 indicates statistical significance.

[0053] 5. Clinical trial results: (1) General data analysis: Control group: 15 males and 15 females; mean age (64.84±3.24) years; mean disease duration (7.22±2.65) years. Study group 1: 13 males and 17 females; mean age (63.55±3.17) years; mean disease duration (7.49±2.78) years. Study group 2: 14 males and 16 females; mean age (63.95±3.28) years; mean disease duration (7.33±2.18) years. Study group 3: 15 males and 15 females; mean age (65.14±3.34) years; mean disease duration (7.33±2.58) years. There were no statistically significant differences in general data among the four groups (P>0.05).

[0054] (2) Analysis of treatment efficacy: The total effective rate after 2 months of treatment was 73.33% in the control group, 96.67% in study group 1, 93.33% in study group 2, and 90.00% in study group 3. Compared with the control group, the total effective rate of each study group was higher. Among them, the total effective rate of study group 1 was significantly different from that of the control group (P<0.01), while the efficacy differences between the other two study groups and the control group were not statistically significant. It can be considered that study group 1 had the best effect on improving the Webster symptom score of Parkinson's patients with anxiety. See Table 1.

[0055] Table 1 Comparison of treatment effects among the four groups [n(%)] Compared with the control group, P < 0.01.

[0056] (3) Analysis of changes in cognitive level scores: After 2 months of treatment, the MMSE scores of all four groups of patients increased compared with those before treatment (P < 0.05). Compared with the control group, the MMSE scores of each study group after treatment were higher than those of the control group, and the differences were statistically significant (P < 0.0001). Among them, the MMSE score of study group 3 increased the most after treatment, and there was no statistically significant difference in the increase among the study groups (P > 0.05). It can be concluded that all four treatments can improve the cognitive level of Parkinson's patients with anxiety, and each study group is better than the control group in improving the cognitive level of Parkinson's patients with anxiety. See Table 2.

[0057] Table 2 Comparison of cognitive level scores among the four groups (scores) ±s) Compared with the control group, P < 0.0001.

[0058] Analysis of changes in quality of life scores: After 2 months of treatment, the GQOIL scores of all four groups increased compared to before treatment (P < 0.05). Compared with the control group, the GQOIL scores of each study group were significantly higher after treatment (P < 0.0001), with the increase in GQOIL score in study group 1 being higher than that in study group 3 (P < 0.0001) and study group 2 (P > 0.05). It can be concluded that all four treatments improved the quality of life of Parkinson's patients with anxiety, and each study group was superior to the control group in improving the quality of life of Parkinson's patients with anxiety, with study group 1 showing the best results. See Table 3.

[0059] Table 3 Comparison of Quality of Life Scores among Four Groups (points) ±s) Compared with the control group, P < 0.0001; ### Compared with study group 3, P < 0.0001.

[0060] Analysis of changes in anxiety scores: After 2 months of treatment, the HAMA scores of all four groups decreased compared to before treatment (P < 0.05). The HAMA scores of each study group after treatment were significantly lower than those of the control group (P < 0.0001), with study group 1 showing the largest decrease in HAMA score. There were no statistically significant differences in HAMA score differences among the study groups (P > 0.05). It can be concluded that all four treatments can improve anxiety in patients with Parkinson's disease and anxiety, and each study group is superior to the control group in improving anxiety in these patients. See Table 4.

[0061] Table 4 Comparison of anxiety scores among the four groups (points, ±s) The experimental results in Tables 1 to 4 show that the traditional Chinese medicine gel formulation of this invention has significant efficacy in treating Parkinson's disease complicated with anxiety. Because the traditional Chinese medicine gel formulation of this invention uses nano-sized lyophilized powder loaded into a gel, it can directly act on the target, exhibiting a targeted sustained-release effect, improving drug bioavailability, thereby reducing the dosage. It is convenient and safer to use via transdermal absorption such as gel patches or ointments. Furthermore, by utilizing natural gels as carriers and other technical means, it achieves sustained and controlled release of the drug.

Claims

1. A traditional Chinese medicine composition for treating Parkinson's disease complicated with anxiety, characterized in that, include: Bupleurum, Cyperus, Ligusticum, Aucklandia, Raw Dragon Bone, Raw Oyster Shell, Scutellaria, Cinnamon Twig, Poria, Pinellia, Arisaema cum Bile, Dried Ginger, Ginseng, Rhubarb, Gypsum, Cuscuta, Cistanche, Lycopodium, Gastrodia, Bombyx Batryticatus, White Peony Root, Atractylodes Macrocephala, Prepared Licorice Root, Styrax, Borneol, and Cinnabar, in a mass ratio of (3-4): (3-4): (3-4): (3-4): (10-20): (10-20): (2-4): (2-5): (4-20): (2-4): (3-4): (1-3): (1-4): (1-3): (3-10): (3-7): (3-7): (3-5): (3-4): (1-4): (3-10): (3-6): (2-3): (1-3): (0.6-2): (0.03-0.1).

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The composition of this traditional Chinese medicine is as follows: Bupleurum chinense 9-12 parts, Cyperus rotundus 9-12 parts, Ligusticum chuanxiong 9-12 parts, Aucklandia lappa 9-12 parts, raw dragon bone 30-60 parts, raw oyster shell 30-60 parts, Scutellaria baicalensis 6-12 parts, Cinnamomum cassia 6-15 parts, Poria cocos 12-60 parts, Pinellia ternata 6-12 parts, Arisaema cum bile 9-12 parts, dried ginger 3-9 parts, ginseng 3-12 parts, rhubarb 3-9 parts, gypsum 9-30 parts, Cuscuta chinensis 9-20 parts, Cistanche deserticola 9-20 parts, Lycopodium clavatum 9-15 parts, Gastrodia elata 9-12 parts, Bombyx mori 3-10 parts, Paeonia lactiflora 9-30 parts, Atractylodes macrocephala 9-18 parts, prepared licorice root 6-9 parts, Styrax benzoin 3-9 parts, borneol 2-6 parts, and cinnabar 0.1-0.3 parts.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The composition of this traditional Chinese medicine is as follows: Bupleurum chinense 10 parts, Cyperus rotundus 10 parts, Ligusticum chuanxiong 10 parts, Aucklandia lappa 10 parts, raw dragon bone 45 parts, raw oyster shell 45 parts, Scutellaria baicalensis 9 parts, Cinnamomum cassia 12 parts, Poria cocos 30 parts, Pinellia ternata 9 parts, Arisaema cum bile 10 parts, dried ginger 8 parts, ginseng 10 parts, rhubarb 6 parts, gypsum 15 parts, Cuscuta chinensis 18 parts, Cistanche deserticola 18 parts, Lycopodium clavatum 12 parts, Gastrodia elata 10 parts, Bombyx mori 6 parts, Paeonia lactiflora 15 parts, Atractylodes macrocephala 12 parts, Glycyrrhiza uralensis 7 parts, Styrax benzoin 6 parts, Borneol 5 parts, Cinnabar 0.15 parts.

4. A traditional Chinese medicine gel preparation for treating Parkinson's disease complicated with anxiety, characterized in that, The mixture is made from a hydrogel carrier in a volume ratio of (60-95):(5-40) and a traditional Chinese medicine compound composition coated with nanoparticles loaded in the hydrogel carrier; the hydrogel carrier is a decellularized bladder matrix; the nanoparticle-coated traditional Chinese medicine compound composition is a traditional Chinese medicine compound composition extracted using the traditional Chinese medicine composition for treating Parkinson's disease with anxiety as described in any one of claims 1-3, and then coated in nanoscale mesoporous polydopamine; the traditional Chinese medicine compound composition refers to: Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong, and... The mixture of volatile oil inclusion complexes extracted from costus root, water extracts of raw dragon bone, raw oyster shell, scutellaria baicalensis, cinnamon twig, poria cocos, pinellia ternata, arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, cuscuta chinensis, cistanche deserticola, lycopodium clavatum, gastrodia elata, silkworm pupae, white peony root, atractylodes macrocephala, and prepared licorice root, and water extracts of bupleurum chinense, cyperus rotundus, chuanxiong rhizome, and costus root, concentrated into nano-scale freeze-dried powder, and a mixture of nano-scale powders made from styrax, borneol, and cinnabar; the mass ratio of the traditional Chinese medicine compound composition to mesoporous polydopamine is (50-100):

1.

5. The traditional Chinese medicine gel preparation according to claim 4, characterized in that, The mesoporous polydopamine has a particle size of 100–200 nm and a mesoporous pore size of 2–50 nm.

6. A method for preparing a traditional Chinese medicine gel preparation for treating Parkinson's disease complicated with anxiety as described in claim 4, characterized in that, Includes the following steps: S1, volatile oils are extracted from Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong and Aucklandia lappa using steam distillation, and the decoction is collected as the first aqueous extract; the volatile oils are then encapsulated with β-cyclodextrin to obtain volatile oil inclusion complexes; S2, raw dragon bone, raw oyster shell, scutellaria baicalensis, cinnamon twig, poria cocos, pinellia ternata, arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, cuscuta chinensis, cistanche deserticola, lycopodium clavatum, gastrodia elata, silkworm pupae, white peony root, atractylodes macrocephala, and prepared licorice root are decocted in water to collect the second aqueous extract; the second and first aqueous extracts are combined and the water is removed to obtain the third aqueous extract; the third aqueous extract is atomized into small droplets using ultrasonic spraying technology and then rapidly sent into liquid ammonia for pre-solidification; then it is transferred to a temperature of -60~5℃ and a pressure of 1.25~1.5KPa for freeze drying to obtain solidified microparticles; the solidified microparticles are ball-milled to obtain nano-sized freeze-dried powder of traditional Chinese medicine compound extract, which is then sterilized by ultraviolet irradiation; S3, Styrax, borneol and cinnabar are poured into a grinder and sheared and crushed to obtain a preliminary powder; the preliminary powder is passed through a 100-mesh sieve and then ball-milled to obtain nano-sized powder of Styrax, borneol and cinnabar, which is then sterilized by ultraviolet irradiation. S4, the volatile oil inclusion complex, the freeze-dried powder of the traditional Chinese medicine compound extract, and the nano-sized powders of styrax, borneol, and cinnabar are mixed to obtain the traditional Chinese medicine compound composition; S5, disperse mesoporous polydopamine in water, add the traditional Chinese medicine compound composition, and stir continuously at room temperature for at least 10 hours; After centrifugation and washing, the precipitate was collected to obtain the nanoparticle-coated traditional Chinese medicine compound composition. S6. The aqueous solution of the decellularized bladder matrix and the nanoparticle-coated traditional Chinese medicine compound composition are mixed at a volume ratio of (60-95):(5-40), and stirred at room temperature to form a gel, thereby obtaining the traditional Chinese medicine gel preparation.

7. The method for preparing the traditional Chinese medicine gel preparation according to claim 6, characterized in that, In step S1, the total mass ratio of Bupleurum chinense, Cyperus rotundus, Ligusticum chuanxiong, and Aucklandia lappa to water is 1:(10-20); the extraction time by steam distillation is not less than 6 hours; when the volatile oil is encapsulated by β-cyclodextrin, the amount of β-cyclodextrin used is 2 to 5 times the mass of the volatile oil.

8. The method for preparing the traditional Chinese medicine gel preparation according to claim 6, characterized in that, In step S2, the total mass ratio of raw dragon bone, raw oyster shell, scutellaria baicalensis, cinnamon twig, poria cocos, pinellia ternata, arisaema cum bile, dried ginger, ginseng, rhubarb, gypsum, cuscuta chinensis, cistanche deserticola, lycopodium clavatum, gastrodia elata, silkworm pupae, white peony root, atractylodes macrocephala, and prepared licorice root to water is 1:(6-10), and the decoction time is 1-3 hours; the number of decoctions includes 1-3 times; after the second and first water extracts are combined, water is removed by alcohol precipitation and / or vacuum drying; the concentration time of the alcohol precipitation is less than 6 hours, the temperature is less than 70°C, and the water extract is concentrated to a relative density of 1.10-1.14 g / ml; the working volume concentration of ethanol used for alcohol precipitation is about 70%; the temperature of the vacuum drying is less than 80°C.

9. The method for preparing the traditional Chinese medicine gel preparation according to claim 6, characterized in that, In step S3, the pre-curing process parameters are: ultrasonic power of 2.5-3.5W, flow rate of the third water extract of 4-8mL / min, and pre-curing time of 6-8min; the freeze-drying process is: drying at -40--35℃ for 24-32h, drying at -30--25℃ for 2-3h, drying at -25--15℃ for 1-3h, drying at -10--5℃ for 1-3h, and drying at 0-5℃ for 1-2h.

10. The method for preparing the traditional Chinese medicine gel preparation according to claim 6, characterized in that, In step S5, the mass concentration of the mesoporous polydopamine dispersed in water is 0.005–0.02 mg / ml; in step S6, when calculating the ratio of the aqueous solution of the decellularized bladder matrix to the nanoparticle-coated traditional Chinese medicine compound composition, the mass concentration of the decellularized bladder matrix is ​​based on 6 mg / ml.

11. The use of the traditional Chinese medicine gel preparation according to claim 4 in the preparation of a drug for treating Parkinson's disease complicated with anxiety.

Images