Source: Li Qiao, He Peiyu, Zhang Dingkun, Pei Zhaoqing, Chen Yipei, Li Zhi, Zheng Chuan.Analysis of the current situation and development strategy of Chuanxiong industry [J]. Chinese Herbal Medicine, 2024, 55(8): 2771-2784.
Ligusticum chuangxiong is the dried rhizome of Ligusticum chuangxiongHort., an umbelliferous plant, which was first published in the Shennong Materia Medica, and is listed as the top grade [1]. Since the Song Dynasty, Chuanxiong has been produced in Sichuan with high quality and good effect, with Pengzhou, Dujiangyan, Shifang, Meishan and other main production areas, is a famous authentic medicinal variety in Sichuan. Chuanxiong has outstanding clinical efficacy, since ancient times, there is a saying that "headache does not leave Chuanxiong", it has the effect of invigorating blood and qi, dispelling wind and relieving pain, and is used more in Chinese patent medicine and traditional Chinese medicine prescriptions, with high medicinal value. In addition, Chuanxiong can also be used in health care products, cosmetics, feed additives, etc., and is one of the traditional Chinese medicines that can be used for health food announced by the National Health Commission. Its above-ground parts are also commonly eaten as vegetables in the main producing areas. Chuanxiong has broad development value in new drug research and development, health product research and development, modern medical clinical treatment, rehabilitation and health preservation.
The cultivation scale of Sichuan Chuanxiong accounts for more than 95% of the country, and it has unique resources and development conditions. In recent years, with the support of national policies and local governments, the Chuanxiong industry has developed rapidly. However, bottlenecks such as excessive heavy metals and lack of intensive processing have restricted the healthy development of the Chuanxiong industry. Based on this, this paper summarizes the research progress of the resource status, chemical composition, pharmacological effects, quality control and related product development of Chuanxiong, and proposes new development strategies and methods to provide scientific and technological support for the high-quality development of Chuanxiong.
1 Research status of Chuanxiong resources and key production technologies
1.1 Resource Overview
Chuanxiong is mainly cultivated artificially, and is mainly produced in Sichuan, Chongqing and other places in mainland China [2]. The cultivation scale of Chuanxiong in Sichuan production areas accounts for more than 95% of the country, mainly concentrated in the western Sichuan Plain with a radius of 100 kilometers such as Pengzhou, Dujiangyan, Shifang and Meishan in Sichuan, especially in Pengzhou, which has the "capital of Chuanxiong in China". In 2015, "Pengzhou Chuanxiong" was registered and protected as an agricultural product by the National Geographical Indication, and in 2022, the cultivation of Chuanxiong in Pengzhou City reached 4 000 hm2 [3], of which Aoping Town is known as the "No. 1 Town of Chuanxiong in China", with a production area of more than 2 000 hm2 and an annual output of more than 8 000 t, ranking first in the country in terms of planting area, output and sales [4]. In September 2021, Pengzhou and Shifang jointly built the Pengshi Chuanxiong Modern Agricultural Park, with a planting area of 6 666.67 hm2 and an annual output of about 30,000 tons [5].
Dujiangyan is a traditional provincial area of Chuanxiong, with a cultivation area of about 333.33 hm2, mainly concentrated in Guangyi Village, Shiyang Town[6], and Pengshan is a new production area developed in recent years, and the planting area of Chuanxiong is increasing year by year, reaching more than 1 333.33 hm2, mainly concentrated in Xiejia Town and other places[7]. At present, there are 2 Chuanxiong bases in the country that have passed the certification of "Good Manufacturing Practice for Chinese Herbal Medicine", which belong to Sichuan New Green Pharmaceutical Technology Development Co., Ltd. and Sichuan New Lotus Traditional Chinese Medicine Decoction Co., Ltd., which have promoted the standardized planting level of local Chuanxiong. There are 2 GI protection products related to Chuanxiong, namely "Dujiangyan Chuanxiong" and "Pengzhou Chuanxiong", and the follow-up regions should actively apply for GI products, and give full play to the basic advantages of "National Geographical Indications", cultivate and build Chuanxiong GI brand, improve the whole industry chain, and make Chuanxiong industry become a local characteristic economic industry.
1.2 Breeding of varieties and Ling seeds
"Vegetative propagation of Ling seeds" is the main method of artificial cultivation of Ligusticum Chuanxiong, and the quality of Ling seeds is the key factor affecting the quality of medicinal materials [8]. After systematic breeding, excellent new varieties such as "Chuanxiong No. 1", "Luxiong No. 1", "New Luxiong No. 1", "Xinluxiong No. 2", "Shuxiong No. 1" and "Shuxiong No. 2" have been obtained. In recent years, a new method of frozen breeding of Poria coria species has emerged in Pengzhou, Shifang and other producing areas, and compared with the traditional "alpine breeding and cultivation in dam area", there is no obvious difference in the yield of medicinal materials produced by Poria spp., which has the advantages of saving cost, time, and labor [9-10], but C. sylvestris still has certain advantages in disease resistance, seedling emergence, plant morphology, and quality of medicinal materials [9-12], and the differences between the two species need to be further studied.
However, in the actual production and application, most of the seeds used by Xiongxiong farmers in the production area are self-propagated and self-used Ba Ling seeds or purchased from different ways, resulting in poor quality, stability and uniformity of the quality and yield of Chuanxiong medicinal materials produced in the same area. The new varieties bred above Chuanxiong have the advantages of high yield, stability and good adaptability, but they have not been popularized and used on a large scale, and there is no Chuanxiong breeding base or germplasm seedling base that provides excellent provenance for large-scale production.
1.3 Key technologies for the production of Chuanxiong
The traditional growth period of Chuanxiong is 270~280 days, which is generally planted in early autumn and harvested during the period from Xiaoman to Miscanthus in the following year [13], but at present, due to the shortage of labor and the guarantee of the growth time of rotational rice, most of the Xiongxiong farmers in most producing areas adopt the method of late planting and early harvesting, which seriously shortens the normal growth period of Chuanxiong [10]. The processing method of Chuanxiong medicinal materials is sun-dried or kang-dried, and the Chuanxiong decoction pieces are formed after "secondary processing". The process from fresh Chuanxiong to medicinal materials to decoction pieces not only increases the production cycle and cost, but also easily causes pollution and loss of active ingredients, which in turn affects the safety and efficacy of clinical medication of Chuanxiong [14].
At present, there have been relevant studies on the fresh processing of Chuanxiong, and it has been preliminarily clarified that the feasibility of processing Chuanxiong while it is fresh [15-16]. Medicinal farmers in Chuanxiong production areas blindly pursue the yield of medicinal materials, and blindly use plant growth regulators in the planting process, such as the product "Palmola" with brassinolide as the main ingredient and the product "Magic Diwang" with choline chloride as the main ingredient; over-reliance on chemical pesticides and excessive application of fertilizers leads to environmental pollution in the planting area, heavy metals exceed the standard and other problems, coupled with the cadmium enrichment characteristics of Chuanxiong, which directly affects the yield, quality and safety of Chuanxiong medicinal materials. At present, cadmium reduction measures such as quicklime [17-20], silicon fertilizer [19,21], microbial fertilizer [21-22], soil conditioner [23-24], and passivator [25] are mainly applied in the cultivation process, which can reduce the heavy metal content of Chuanxiong medicinal materials to a certain extent.
Sichuan is the area with the largest planting scale, the largest yield and recognized authentic quality in mainland China. The problem of the planting end of Chuanxiong is the key reason restricting the development of Chuanxiong industry. First, the labor cost is too high. According to the data of the Chinese herbal medicine world, the labor cost accounts for more than 50% of the planting cost of Chuanxiong and the labor shortage, resulting in the extensive management of Chuanxiong cultivation and the phenomenon of late planting and early harvesting. Second, the research on Chuanxiong breeding needs to be strengthened urgently. It can be seen from Table 1 that there have been many varieties of Chuanxiong for yield and stability, but the correlation between the breeding method and the quality of medicinal materials, germplasm and heavy metal content of Chuanxiong has not been studied in depth.
The proportion of the breeding methods in the dam area has reached 53%, and although there are some literature reports on the quality differences between the dam and the mountain species, the real differences and internal mechanisms between the two species still need to be further studied. It was found that the germplasm of Chuanxiong was also one of the important reasons affecting the content of cadmium in Chuanxiong [26], and revealing the cadmium enrichment characteristics of Chuanxiong and improving Chuanxiong varieties would be the focus of the breeding of excellent Chuanxiong varieties. In addition, the cultivation management of Chuanxiong in different production areas, such as cultivation density, fertilizer and pesticide application times and amounts, planting and harvesting time, etc., are different, and further accelerating the standardization and mechanization process of Chuanxiong cultivation management is the key to improve the production efficiency of Chuanxiong and realize the large-scale production of Chuanxiong.
2 Research on the chemical composition and pharmacological activity of Chuanxiong
The active ingredients of Chuanxiong mainly include phthalides [27-28], phenolic acids, alkaloids, and polysaccharides, and have good pharmacological activities against the cardiovascular and cerebrovascular system [29], nervous system [30], respiratory system [31], liver and kidney [32-33], etc., and are mainly analgesic [30,34-36], anti-inflammatory [37], antioxidant [38-40], antitumor [41-42], anticoagulant [43-44], antidepressant [45-46], and anti-aging [ 47-48], see Figure 1.
Volatile oil is the main pungent part of Ligusticum Chuanxiong [49], mainly containing phthalides represented by Lime litolactone [50], and terpenes such as carcinene and α-Ningne [51], and phthalides such as Ligusticum lidolide, Ligustolide A, and butene phthalide are the material basis for the pungent taste of Ligusticum ligusticum volatile oil [49]. Phthalides are important active components of Ligusticum Chuanxiong [52], which are closely related to the effects of Ligusticum Chuanxiong in invigorating blood circulation and dispelling stasis and qi, dispelling wind, dampness and relieving pain. At present, more than 70 monophthalide derivatives and more than 30 dimer phthalide derivatives have been identified [53], and phthalide dimers often exist in the form of racemates [54].
The contents of Rhizomericolide, Ligustolide H, Ligustolide I, Angelica sinensis A and other products were high and had good biological activity, which was the material basis for the upward movement of Ligusticum Chuanxiong. Phenolic acids such as ferulic acid, chlorogenic acid, and caffeic acid have been widely reported, and have various pharmacological effects such as antioxidant, antiplatelet aggregation, antitumor, and brain protection [55]. More than 40 alkaloids have been isolated from Chuanxiong [56-59], all of which are small molecule compounds with low content, and related pharmacological studies have mainly focused on Chuanxiongzine, which has a wide range of pharmacological effects, such as anti-cerebral ischemia, anti-myocardial ischemia, anti-myocarditis, protection of vascular endothelial cells, and protection against acute renal injury [60]. The polysaccharide content of Chuanxiong is about 5.71%, which is mainly composed of monosaccharides such as glucose, galactose, arabinose, xylose, rhamnose, and mannose [61-62], which has the functions of antibacterial, immune regulation, and antioxidant.
The unclear pharmacodynamic substances of traditional Chinese medicine is a key problem restricting the development of the traditional Chinese medicine industry, and it is the premise for the quality control, clinical application and in-depth development and utilization of Chuanxiong to clarify the chemical substances closely related to the functional properties of traditional Chinese medicine by systematically carrying out basic research on the pharmacodynamic substances of traditional Chinese medicine. However, at present, the relevant research has not been carried out in depth, and there are few studies on cells, pathways and genomes, and it is necessary to strengthen the in-depth research on the pharmacodynamic mechanism of Chuanxiong.
3 Research on quality control of Chuanxiong
The 2020 edition of the Chinese Pharmacopoeia contains the traits, microscopic identification, and physicochemical identification of Chuanxiong, limits its alcohol-soluble extracts, and uses ferulic acid as the quality control component of Chuanxiong, the amount of which is determined by high performance liquid chromatography (HPLC) and stipulates that it shall not be less than 0.10%[1]. In addition to the traditional trait identification, thin layer chromatography [63-64], HPLC [65-66], gas chromatography mass spectrometry [67], HPLC-mass spectrometry [68], Fourier transform infrared spectrometry [69], paper spray mass spectrometry [70], terahertz time-domain spectroscopy [71], biomimetic sensory intelligence analysis [72], Insertion/Deletion molecular markers [73] and other modern new identification methods are also gradually used in the identification of Chuanxiong.
Ferulic acid is widely used in a variety of Chinese medicinal materials such as Umbelliferae and Ranunculaceae, and it is only used as a quality control index of Chuanxiong, which is not strong in characteristics and difficult to comprehensively evaluate the quality of Chuanxiong medicinal materials. Literature studies often evaluate the quality of Chuanxiong medicinal materials based on multiple indicators [74-76]. In addition, studies have shown that the content of volatile litolactones and Yangxionglactone A is relatively high [75], which is not only the material basis for the pungent taste of volatile oil of Ligusticum Chuanxiong [49], but also the material basis for the upward movement of Ligusticum chuanxiong as a "medicine" [77]. In view of the lack of physical and chemical indicators and the lack of decoction piece standards in the current commodity specifications and grades of Chuanxiong medicinal materials, it was found that there was a correlation between the appearance and characteristics of Chuanxiong medicinal materials, such as individual weight, maximum diameter, surface and cross-sectional color, and the content of ferulic acid, liminolactone, and Yangxionglactone A content [78-79].
According to literature statistics, from 2004 to 2017, the cadmium exceedance rate of cadmium was as high as 87.99% [80]. In 2017, the Ministry of Commerce of China reported that the total export volume of Chuanxiong ranked 9th in the export of Chinese herbal medicines in the mainland, and the export volume of Chuanxiong in 2017 was 4 614.57 t, and the export volume gradually declined since then, with an annual export volume of less than 3 000 t, see Figure 2. The excessive cadmium of the heavy metal in Chuanxiong has become a barrier restricting Chuanxiong to foreign markets. In recent years, Chuanxiong has been rejected by foreign countries many times due to excessive heavy metal standards, and has been exported six times due to heavy metal problems [81]. In response to the above problems, the importing countries of Chinese herbal medicines have successively formulated extremely strict access standards to restrict the entry of Chinese herbal medicines, which has seriously hindered the important international trade of the mainland and damaged the international image of traditional Chinese medicine.
The quality control components of medicinal materials should be closely related to the functional attributes of traditional Chinese medicine. The main pharmacodynamic components of Chuanxiong were phthalein volatile components such as Lizolactone and phenolic acids such as ferulic acid, which had a certain correlation with the pharmacodynamic effect of Chuanxiong [82], the grade of medicinal materials [78], the color of the powder [72], and the "pungency" response value of volatile oil [49]. The content of the alkaloid component Ligustrazine in most Ligusticum Chuanxiong medicinal materials was significantly lower than the detection limit, and the content was extremely low less than 1/10,000 [83-84], although Ligustrazine Chuanxiong has a wide range of pharmacological effects, it is still controversial whether it can represent the main active ingredient of Chuanxiong medicinal materials because of its extremely low content, so it is still debatable as a quality evaluation component of Chuanxiong medicinal materials.
The revision of the index components for the determination of Ligusticum Chuanxiong still needs to be further studied, and the safety, efficacy and measurability of Ligusticum Chuanxiong need to be considered. Comparing the limit standards of heavy metal cadmium in various countries/regions or organizations, it is found that the cadmium limit standard of the "Green Industry Standard for the Import and Export of Medicinal Plants and Preparations" in mainland China is at the most stringent level. The purpose of setting the limit standard is to standardize the production process of planting and processing medicinal materials and prevent human pollution [85]. However, it was found that the cadmium content of Chuanxiong medicinal materials still exceeded the industry standard when the cadmium content in the cultivated soil met the relevant standards, and the atmospheric environment and irrigation water of the base were not polluted [13], indicating that Chuanxiong itself has a strong ability to enrich cadmium.
The current research on heavy metals mainly focuses on the current situation of cadmium pollution and cadmium reduction strategies, while ignoring the cadmium accumulation and ecological health risk assessment. Therefore, comprehensively improving the research on the quality standards of Chuanxiong, improving the commodity specifications and grade standards of Chuanxiong, and formulating scientific and reasonable standards for medicinal materials play an important role in ensuring the safety and effectiveness of the clinical use of Chuanxiong, and at the same time can effectively standardize the market of Chuanxiong medicinal materials and achieve real high quality and high price.
4 Current status of clinical research and related product development of Chuanxiong
4.1 Current status of clinical research on the prescription and preparation of Chuanxiong as the main drug
As a well-known traditional Chinese medicine for invigorating blood and qi, dispelling wind and relieving pain, Chuanxiong is often used in clinical practice for chest paralysis and heartache, chest and flank tingling, swelling and pain, menstrual irregularities, amenorrhea and dysmenorrhea, abdominal pain, headache, rheumatism and paralysis pain, etc. At present, the clinical application of traditional Chinese medicine preparations with Chuanxiong as one of the prescription flavors mainly focuses on the clinical efficacy of treating cardiovascular and cerebrovascular diseases such as coronary heart disease and angina pectoris [86] and anti-migraine [87], as shown in Table 2.
4.2 Research on relevant proprietary Chinese medicines
4.2.1 Analysis of Chinese patent medicines containing Chuanxiong in the Chinese Pharmacopoeia
Chuanxiong is recorded in the 1963~2020 edition of the Chinese Pharmacopoeia, and the 2020 edition of the Chinese Pharmacopoeia contains 245 kinds of Chinese patent medicines containing Chuanxiong, accounting for 16.8% of the Chinese patent medicines, compared with the 2015 edition of the Chinese Pharmacopoeia, 12 new kinds, of which there are 53 preparations with more than 15% of the prescription volume of Chuanxiong, with Tianshu capsules, Tianshu tablets, Dachuanxiong oral liquid and other Chinese patent medicines containing the highest prescription amount of Chuanxiong, followed by Shu Chest Tablets, Shu Chest Capsules, Shu Chest Granules, Naoan Capsules, etc., to invigorate blood, remove stasis, The main effects are channeling and regulating menstruation (Table 3).
In terms of dosage forms, there were 11 dosage forms involved in the Chinese patent medicines containing Chuanxiong, mainly pills (80), capsules (54), tablets (41) and granules (30), followed by mixtures (17) and ointments (10), while the number of liquor, powder, tincture, syrup and liniment was small, and there was a large space for dosage form innovation. Distillation extraction + water decoction (14.5%) followed, followed by ethanol permeation extraction (6.5%), ethanol reflux extraction + water decoction (5.3%), ethanol reflux extraction (4.9%), and the other 12 extraction methods accounted for only 7.8% in total.
4.2.2 Analysis of the output value of large varieties of Chinese patent medicines containing Chuanxiong
Chuanxiong decoction pieces have been included in the "National Medical Insurance Catalogue (2022) Edition" and "National Essential Medicines List (2018 Edition)", and 40 Chinese patent medicines containing Chuanxiong have been included in the "National Essential Medicines Catalogue (2018 Edition)", accounting for 14.9%, mainly in the fields of internal medicine, gynecology, and orthopedics and traumatology, including 22 internal medicine, 6 gynecological drugs, 6 orthopedic drugs, 3 ophthalmic drugs, 2 otolaryngology drugs, and 1 surgical drug.
The sales of large varieties of Chinese patent medicines mainly containing Chuanxiong were queried through the Pharmaceutical Rongyun Database, and the total retail sales of pharmacies and hospitals in the country from 2015 to 2020 were counted, as shown in Table 4. Judging from the data from 2015 to 2020, the retail sales of pharmacies and hospitals have increased year by year, and they are large varieties with an average annual sales of up to 500 million yuan, and the cumulative output value has been 10 billion yuan since it was listed for 26 years. The varieties with average annual sales of more than 50 million yuan are Xinnaokang Granules, Tongmai Granules, and Yixinshu Tablets, and the rest of the varieties with average annual sales of more than 10 million yuan are Huoxue Tongmai Tablets, Lemai Granules, Compound Chuanxiong Capsules, etc., and their main functions are cardiovascular diseases such as coronary heart disease, angina, etc.
4.3 Chuanxiong related health products and other derivative products
4.3.1 Health food
Although Chuanxiong has not entered the catalogue of medicinal and edible homologous varieties, it is a traditional Chinese medicine that can be used for health food. According to the database query of the Pharmaceutical Intelligence Network, there are about 82 health foods containing Chuanxiong, see Table 5. From the perspective of time span, one health care product has been approved as early as 1997, which has the health care effect of anti-fatigue. In the following ten years, dozens of health care products including oral liquids, capsules, granules, pills and tablets have appeared. According to the number of products corresponding to the health care effect, it can be seen that the health food containing Chuanxiong is mainly used to enhance immunity, beauty, improve sleep, and assist in regulating blood lipids.
The development of products mainly focuses on enhancing immunity and removing melasma, followed by regulating blood lipids and improving sleep.
4.3.2 Cosmetics
Chuanxiong can inhibit tyrosinase activity and has emollient, whitening and freckle removal effects [106-107], and can be used as a natural additive in cosmetics. The notice of the State Medical Products Administration on the issuance of the "Catalogue of Names of Used Cosmetic Raw Materials" (No. 62 [2021]) clarifies that "Chuanxiong root powder", "Chuanxiong root extract", "Chuanxiong extract", "Chuanxiong oil" and "Chuanxiongzine" can be used as cosmetic raw materials. Using "Chuanxiong" as the keyword, the filing information of domestic non-special-purpose cosmetics of the State Drug Administration was retrieved, and a total of 28 kinds of current effective filing information were queried. Product forms include essential oils, toners, serums, toilet waters, etc.
4.3.3 Other Derivatives
There were 16 kinds of the same components in the volatile oil of roots, stems, leaves, and flowers, and all of them had the highest relative contents of Ligusticum ligusticum and Ligusticum nichuanxionglactone [108]. Its aboveground parts, known as "Miwu" in ancient times, accounted for 75% of the fresh mass of the whole plant, and were fragrant, and were often worn as vanilla [109]. Its chemical composition is similar to that of Chuanxiong herbs [110], and contains a large number of phthalides with novel structures and significant biological activities [111-112], among which the mass fractions of Lime lifloride and butylphthalide are 0.064 2%~0.263 3% and 0.005 7%~0.032 5%, respectively [112].
Chuanxiong seedlings and leaves have the habit of being eaten as vegetables in the Chuanxiong production area, and are also exported to South Korea, Japan, Singapore, Vietnam and other countries [113];In addition, they can be soaked in water instead of tea, used in health care products, beauty cosmetics, livestock green fodder, edible spices, etc.[114];Sichuan New Green Pharmaceutical Co., Ltd. was approved by the Sichuan Provincial Department of Science and Technology to establish the "Sichuan Chuanxiong Engineering Technology Research Center", and developed a series of health products according to the efficacy of Chuanxiong, such as Chuanxiong toothpaste, shampoo, facial mask, etc.; Chuanxiong sachets, Chuanxiong concentrated essence and other products, as well as stews, wine, tea, mixed vegetables and other more than 30 kinds of Chuanxiong specialties [115].
With the continuous expansion of the traditional Chinese medicine market and the increase in the demand for Chinese herbal medicines, the development and utilization of Chuanxiong in the field of drugs and health products has gradually increased. Through the analysis of the clinical research and related product development status of Chuanxiong, it can be seen that the application and development status of Chuanxiong show the following characteristics:
(1) The main clinical application of Chuanxiong is cardiovascular and cerebrovascular diseases, a variety of headaches, and is often used to treat gynecological diseases such as irregular menstruation, amenorrhea, dysmenorrhea, etc., according to Table 2, the effective rate is 71.6%~98.5%. At present, the sales of large varieties of traditional Chinese medicine, mainly Chuanxiong, are increasing year by year, and the functional indications are still mainly cardiovascular diseases such as coronary heart disease and angina.
(2) Chuanxiong is a typical traditional Chinese medicine variety with a large number of pill powders, accounting for 41.6% of the medicine in the form of powder, and the form of decoction pieces is determined by its "medicinal properties", and the volatile oil components of Chuanxiong are an important material basis for Chuanxiong to invigorate blood and dispel blood stasis and qi, dispel wind, dryness and dampness and relieve pain, which further illustrates the rationality of Chuanxiong's traditional belief that "oily and aromatic ones are better".
(3) The application scope of Chuanxiong has gradually expanded, and in addition to medicinal use, it is also widely used in health care products, cosmetics, food, traditional Chinese veterinary medicine and other fields. Through the further analysis of the active ingredients and pharmacological effects of Chuanxiong, the research and development of daily chemicals, cosmetics and health care products of Chuanxiong further showed the increase in scientific research investment of Chuanxiong, and at the same time drove the increase of market demand and planting area.
(4) The development of Chuanxiong health products is still in its infancy. Taking food development as an example, 1 059 and 364 domestic health food data were queried by Yaozhi data, while only 82 were Chuanxiong, while 4 059 and 234 domestic cosmetics were queried by Yaozhi data, while only 139 were Chuanxiong.
5 Analysis of Chuanxiong-related patents
As of September 6, 2023, a total of 54 4446 Chuanxiong-related patents were retrieved, and a total of 43 833 patent families were retrieved after simple family merger, of which 38 239 were Chinese patents, accounting for 87.24% of the world's Chuanxiong patents, followed by 1 3772 in Japan and 1 201 in South Korea. Figure 3-A shows that since 2004, the number of global Chuanxiong patent applications has shown an accelerated growth trend year by year, reaching a historical peak of 4 691 in 2015, and has been slowly declining year by year.
The structure of patented technology can reflect the technological development direction and focus of the industry, and through the statistics of the International Patent Classification (IPC), the main technologies involved in Chuanxiong are concentrated in the field of medicine (A61) and food (A23). In terms of sub-categories, A61K and A61P have the most applications, accounting for 46.10% and 43.07% of the total number of patent applications respectively, which can be regarded as core technology fields, while the application rate in other fields accounts for less than 5%, see Figure 3-B. medical preparations 25.76%.
It can be seen that the current active technology categories of Chuanxiong are mainly A61K and A61P, and the surface of Chuanxiong Chinese herbal medicines, Chinese medicine decoction pieces, Chinese medicine formula granules, Chinese patent medicines, etc. are the current technology research and development hotspots of Chuanxiong, but the development efforts in the fields of health care products and cosmetics are insufficient, consistent with the previous results, and technological innovation urgently needs to make up for the shortcomings of the industrial chain in the field of big health product development and deep processing.
6 Problems and development strategies in the development of Chuanxiong industry
6.1 Development Strategy
The Chuanxiong industry chain can be divided into three industrial pillars, the primary industry mainly includes the planting and primary processing of Chuanxiong, the secondary industry mainly includes the deep processing and product research and development of Chuanxiong, and the tertiary industry mainly includes Chuanxiong-related health care and cultural tourism services. First of all, formulate special support policies. In view of the lack of scientific and technological level of Chuanxiong agriculture and the non-standard planting and production, the government should introduce corresponding policy support for the construction of Chuanxiong breeding base and the construction of national Chuanxiong industrial park; Second, increase the leadership of science and technology.
In view of the high labor cost of Chuanxiong planting and the accelerated loss of labor, the research on mechanized planting and harvesting of Chuanxiong should be strengthened and popularized and applied. Third, we need to increase investment in basic research. In view of the problems of excessive cadmium of heavy metals, easy degradation of germplasm, large quality differences, underutilization of non-medicinal parts, and the initial stage of health care product development, it is necessary to actively build a scientific research and innovation platform to carry out in-depth research on the mechanism of heavy metal enrichment effect of Chuanxiong, the microecological mechanism of Yuling rejuvenation, the development of non-medicinal resources, and toxicological safety, so as to lay a solid foundation for the rational application of Chuanxiong, the formulation of standards and the development of health products.
6.2 Problems and Solutions
6.2.1 Risk prevention of excessive cadmium of heavy metals to ensure the quality and safety of Chuanxiong medicinal materials
The heavy metal cadmium has a strong enrichment effect on Chuanxiong, coupled with the increase of planting years, the abuse of agricultural inputs and serious soil pollution, etc., resulting in the widespread phenomenon of excessive heavy metal cadmium in Chuanxiong. According to reports, the detection level of cadmium in Chuanxiong can reach up to 1.49 mg/kg, which is about 30 times higher than the standard [26], far exceeding the 2020 edition of the Chinese Pharmacopoeia, green industry standards, EU standards and World Health Organization standards, which has brought adverse effects on the safety of Chuanxiong products and the healthy development of the industry.
At present, there are a variety of measures to reduce the cadmium content of Ligusticum Chuanxiong production, such as the application of quicklime [17-20], silicon fertilizer [19,21], microbial fertilizer [21-22], soil conditioner [23-24], passivator [25] and other measures, but there are problems such as unstable cadmium reduction effect, difficult to promote, and easy to lead to secondary pollution. The excessive cadmium of the heavy metal in Chuanxiong is a barrier restricting Chuanxiong to enter the international market. On the one hand, by establishing reasonable standards to regulate the planting and processing of Ligusticum Chuanxiong, vigorously promoting ecological planting, strengthening the prevention and restoration of soil pollution, reducing the use of chemical fertilizers and pesticides, and implementing crop rotation, on the other hand, to solve the dilemma of Ligusticum Chuanxiong industry from the perspective of germplasm resources, to clarify the effect and mechanism of C. Chuanxiong on heavy metal cadmium enrichment by strengthening basic research, and to screen new varieties with low cadmium enrichment ability. In addition, the risk prevention and assessment of cadmium heavy metal should be strengthened, and the safety of Chuanxiong should be reasonably regarded in combination with the usage and dosage of Chuanxiong and its own cadmium enrichment effect, and a reasonable cadmium limit standard should be formulated.
6.2.2 Take the research of classic prescriptions as an opportunity to increase the development of new drugs for Chuanxiong
According to the statistics of the Healthy China Action (2019-2030), there are 270 million hypertension patients, 13 million stroke patients, and 11 million coronary heart disease patients in China, and the burden caused by four types of chronic diseases, such as cardiovascular and cerebrovascular diseases, accounts for more than 70% of the total disease burden, which has become an important factor restricting health expectancy and improving life expectancy. The research and development of new drugs based on Chuanxiong, a "blood qi medicine", is very corresponding to this social background. The 2020 edition of the Measures for the Administration of Drug Registration adds evidence for the separate classification of the registration of ancient classic prescriptions and the evaluation of human experience, and clearly points out the requirements for the registration and application of new drugs of ancient classic prescriptions for traditional Chinese medicine.
Since 2018, the State Administration of Traditional Chinese Medicine has successively released the "Catalogue of Ancient Classic Prescriptions (First Batch)" and "Catalogue of Ancient Classic Prescriptions (Second Batch)", of which there are 14 and 11 classic prescriptions containing Chuanxiong respectively. There have been detailed reports on the materia medica research of Chuanxiong in the classic formula, which provides some background information for the subsequent research and development of Chuanxiong classic formula. In the later stage, we should pay attention to and strengthen the basic research of innovative classic formulas such as Chuanxiong Wenjing Soup, Taohong Siwu Soup, and Xiaoxuming Soup, so as to improve the overall application degree in innovative Chinese medicine drugs, improved new drugs of Chinese medicine, and in-hospital preparations.
6.2.3 Pay attention to the research on the functional positioning of Chuanxiong and optimize the health industry system of Chuanxiong
In addition to the medicinal use, Chuanxiong has a wide range of applications including health care products, cosmetics, food, traditional Chinese veterinary drugs and other fields, covering a wide range, but the big health industry is still in its infancy, and the number of patents in health food and related fields is small. Although Chuanxiong has a history of eating and eating habits in its production area, most of its aboveground seedlings are eaten as vegetables, and the rhizomes of Chuanxiong have strong medicinal efficacy and certain food contraindications, so it is necessary to further carry out systematic safety evaluation research to determine reasonable functional positioning and health care application.
Therefore, the large health industry system of Chuanxiong can be optimized in combination with the characteristics of Chuanxiong industry:
(1) Non-medicinal parts can be fully developed and utilized. At present, the development of non-medicinal parts of traditional Chinese medicine is mainly focused on clinical application, new drug discovery and substitution, tea and health products, daily chemical products or animal husbandry, etc., such as the related products developed according to the anti-inflammatory and pain-relieving effects of Panax notoginseng flowers and leaves have been applied to clear the throat and moisten the throat, and ginseng leaves and Eucommia ulmoides leaves have been included in the 2020 edition of the Chinese Pharmacopoeia as alternative drugs for ginseng and Eucommia ulmoides. The aboveground part of Chuanxiong accounts for about 75% of the fresh mass of the whole plant, which is similar to the chemical composition of Chuanxiong medicinal materials and has a long edible history in its production area, but only a small number of Chuanxiong seedlings are eaten as vegetables in its production area, and the rational development of non-medicinal parts needs to be strengthened.
(2) Improve the industrial chain of Chuanxiong, and improve the ability of deep processing and achievement transformation of products. The product system of Chuanxiong is still dominated by Chinese herbal medicines, decoction pieces and formula granules, and Chinese patent medicines, while other derivative products are relatively simple, with low added value of products, narrow promotion channels, and weak marketing strategies. In addition, the volatile oil content of Chuanxiong is about 1% and contains a large number of medicinal ingredients, and the development of aromatherapy and fragrance products such as essential oils or compound essential oils is also a new way for the development of Chuanxiong health products.
The high-quality development of Chuanxiong industry needs to integrate the forces of local governments, enterprises, universities and scientific research institutions to carry out comprehensive innovation in the whole technology chain, the whole product chain and the whole industrial chain of Chuanxiong, and form a new industrial system with Chuanxiong planting and primary processing as the primary industry, intensive processing and product research and development as the secondary industry, and health care and cultural tourism services as the tertiary industry. Do "fine" agriculture. Accelerate the establishment of innovative scientific research platforms such as Chuanxiong Science and Technology Academy and Chuanxiong Research Institute, focus on the study of outstanding problems in production practice such as the risk prevention and control of heavy metal cadmium and the easy degradation of germplasm of Chuanxiong, strengthen the construction of Chuanxiong seed and seedling bases and standardized production bases, do a good job in the selection and breeding of Chuanxiong varieties, standardized planting, green ecological planting, etc., and form demonstration and promotion, so as to ensure the quality and safety of Chuanxiong medicinal materials from the source.
To be a "strong" industry. Strengthen the quality construction of the source of Chuanxiong, actively promote the research on the demonstration project of the management norms and quality standards of the whole industrial chain of Chuanxiong Chuanxiong, and improve the quality of Chuanxiong products; cultivate leading enterprises, promote the digital transformation and upgrading of industrial manufacturing of Chuanxiong products, and improve the consistency of production scale and quality; attach importance to intensive processing, carry out in-depth research on the innovation of Chuanxiong processing and processing technology of Chuanxiong while it is fresh, and develop a series of market-competitive new decoction pieces such as freeze-dried and pressed Chuanxiong; Research on international standards to promote the modernization, standardization, industrialization and international development of Chuanxiong formula granule industry; promote the research and development of new drugs of Chuanxiong by combining the secondary development of classic prescriptions, the examination of famous and old Chinese medicine prescriptions, and the prevention and treatment of major diseases; the establishment of Chuanxiong Industry Alliance to support the combination of production, education and research, and accelerate the research and development of Chuanxiong health products. To be a "special" tertiary industry.
Accelerate the construction of the soft power of Chuanxiong brand such as theory, culture, planning, trading, and service, and at the same time enhance the awareness of brand development and intellectual property protection. Combining rural revitalization and ecological health care, deepen the cooperation between schools, localities and enterprises, build a demonstration area for agricultural modernization in Chuanxiong, pay attention to the excavation and innovation of the historical and cultural connotation of the Chuanxiong Road real estate area, build a Sichuanxiong theme health care town and cultural tourism demonstration park, and accelerate the integration of Chinese herbal medicine (Chuanxiong) museum, health care center, theme homestay and other integration projects. Under the guidance of policies and the support of the government, we will unite scientific research units and local enterprises, and take agriculture as the basic support, extend the industrial chain, industrial integration and technological innovation of Chuanxiong, build a modern whole industrial chain system of Chuanxiong, and promote the high-quality development of Chuanxiong industry and rural revitalization.