月度归档 2024年4月9日

　　Correspondent Tang Tang Our reporter Zhang Wei

　　When people get sick, they often have to hang water to take medicine. However, after the drug enters the human body, it is not smooth sailing to reach the designated position, stay for a longer time, be better absorbed, and avoid being accidentally injured by friendly forces.

　　In recent 20 years, more and more new nano-pharmaceutical preparations have flooded into the market, and nano-liposomes with the name of "small steamed buns" in the carrier have emerged as the times require. This kind of vesicle with nanometer particle size formed by lipid bilayer can wrap drugs with great toxic and side effects, poor stability and rapid degradation. By fusing with the cell membrane, the carried drugs are concentrated in the focus, so as to achieve targeted administration, and at the same time, the curative effect can be improved, the toxicity can be reduced, and the stability can be enhanced.

　　Recently, Professor Gu Ning of Southeast University led a team to break the technical barriers abroad, overcome the key technologies of nano-lipid materials, built the first domestic and largest production line of lipid nanoparticles in the world, and won the first prize of scientific and technological progress in Jiangsu Province.

　　Then, how does this nano-scale "little one" take on the heavy responsibility of "packaging" and "transporting" through-train service? What other unknown uses do nanoliposomes have besides their great potential in drug carriers?

　　Known as the secret weapon of "rejuvenation"

　　The formation of liposomes is due to the self-assembly properties of a substance called phospholipids. Phospholipid is an amphiphilic substance, one end is hydrophilic and the other is lipophilic. Due to the particularity of its molecular configuration, phospholipid will spontaneously assemble into a bimolecular membrane structure in water, and part of it will be wrapped inside, which is usually called "vesicle".

　　The earliest liposomes were naturally formed in water. After scientists discovered its special skills, they tried to synthesize phospholipid compounds by artificial methods in order to achieve the purpose of mass production. The diameter of liposomes is usually tens of nanometers to tens of millimeters, and "nano-liposomes" are liposomes with nanometer particle size.

　　The membrane structure of lipid nanomaterials is very close to the cell membrane, which provides convenience for drug delivery and absorption. Therefore, liposomes can wrap the effective components and introduce them into cells, so that the effective components can easily enter cells.

　　In many common drugs, liposomes are responsible. Such as antineoplastic drugs, drugs targeting reticuloendothelial system, protein and nucleic acid drugs, antibacterial drugs, anti-inflammatory hormone drugs, etc. Moreover, the drug with liposome as the carrier "skin is not delicate" can be administered in any way, including intravenous injection, subcutaneous and intramuscular injection, oral administration, pulmonary administration and skin administration.

　　"The size of liposomes is related to the route of administration and drug release rate, but nano-sized liposomes have obvious advantages as drug carriers." Professor Gu Ning told reporters that daunorubicin liposomes, for example, have a particle size of 60-mdash; 120 nm, because of its small particle size, it is not easily recognized by phagocytes of reticuloendothelial system after entering the blood circulation, so it can stay in the blood circulation for a long time. At the same time, the pharmaceutical preparation has no obvious cardiotoxicity.

　　In recent years, more and more nanoliposome drugs have flooded into the international market and become the fastest-growing high-end pharmaceutical preparation in the world. Nanoliposomes not only play an important role in the pharmaceutical industry, but also act as a professional "courier" in cosmetics. It can keep the activity of cosmetics well, so that growth factors and other ingredients can enter the stratum corneum faster and more completely, thus enhancing the cell repair ability. Therefore, liposome encapsulation is known as the secret weapon of "rejuvenation".

　　Oil-loving and hydrophilic "amphiphilicity" increases the difficulty of mass production

　　In recent years, in the international pharmaceutical field, dexterous and multifunctional nanoliposomes have almost become "online celebrity".

　　At present, a total of 29 nanoliposome drugs have been approved for marketing in the world. In addition, there are 87 nanoliposome drugs in clinical research stage and 132 nanoliposome drugs in preclinical research stage. Among them, there are 13 nanoliposome drugs approved for marketing by the US Food and Drug Administration (FDA).

　　In sharp contrast, only three nanoliposome drugs in China have been approved for production, namely paclitaxel liposome for injection, doxorubicin hydrochloride liposome and amphotericin B liposome for injection.

　　But 10 years ago, the related drugs and cosmetics in China were blank, and the people in China could not touch them at all, because the key technologies of lipid nanomaterials were in the hands of foreigners.

　　The international market share of nanoliposome drugs is increasing year by year, but the industrialization development in this field in China has been slow. "The reason is that the lipid nanomaterials needed by nanoliposome drugs are completely imported, and their prices far exceed the raw materials themselves; Second, the quality, purity and stability of domestic liposome pharmaceutical preparations need to be improved; Third, the assembly technology of lipid nano-materials and the preparation technology of lipid nano-drugs have high requirements and great difficulties. " Professor Gu Ning told reporters.

　　In 1970s, when liposomes were first used as drug carriers, they were once ignored because of their extremely unstable structure and low drug encapsulation efficiency. With the in-depth study of liposomes, the existing problems have been solved initially. In the early 1990s, economical and efficient anti-fungal and anti-cancer drug liposomes were put into the market, which greatly promoted the research and development of liposomes.

　　Lipid nano-materials have unique hydrophilic and lipophilic "amphipathy", which makes it possible to add lipophilic and hydrophilic drugs and active ingredients to the same drug at the same time.

　　However, researchers have also found that the amphiphilic nature of lipid nanomaterials is a double-edged sword, which not only provides convenience for drug loading, but also increases the difficulty of mass production. Therefore, the preparation process of lipid nano-materials is complex, which makes it difficult to remove impurities, and it is difficult to purify intermediates and products, so it is difficult to achieve mass production.

　　It is also a treasure to use "the wind blows on both sides"

　　The raw materials for preparing nanoliposomes are not complicated, but if you can’t master the doorway, you can’t make qualified nanoliposomes.

　　Well-made liposomes have a phospholipid bimolecular shell, which is very similar to the structure of cell membrane, and they are very small, and their diameters are basically below 150 nanometers, which is helpful for the penetration of active substances.

　　To realize the localization of lipid nanomaterials, the synthesis process is particularly important. Therefore, Professor Gu Ning’s team put forward an innovative new process for synthesis and purification of lipid nanomaterials. Through self-made separation filler and independent separation and purification technology, they realized the industrialization of high-purity lipid nano-medicinal carrier materials.

　　Lipid nano-materials are hydrophilic at one end and lipophilic at the other, which seems to be "the wind blows on both sides", so how to use them well is also very particular. After repeated experiments, researchers finally found a "trick up my sleeve". "We creatively put oil-soluble drugs on the oleophilic outer layer and water-soluble drugs on the hydrophilic inner layer, giving full play to the role of drugs, and truly fostering strengths and avoiding weaknesses." Professor Gu Ning said.

　　According to Professor Gu Ning, they developed a new process for the synthesis and purification of lipid nanomaterials, which used a "one-pot" reaction to prepare key intermediates, and the yield was doubled. At the same time, the liposome coordination technology broke through the key bottleneck of the assembly of glycyrrhizic acid drug phospholipid complex. Diammonium glycyrrhizinate was complexed with phosphatidylcholine, a lipid material, to form a lipid complex, which greatly improved the lipophilicity of glycyrrhizic acid and made it easier to cross the multiple membrane structures of the digestive tract and enter the blood circulation, effectively solving the problem of low oral bioavailability of glycyrrhizic acid.

　　After the success of the project, the price of domestic lipid nano-materials dropped significantly, which significantly reduced the overall cost of liposome drugs. In addition, lipid nanoparticles technology has been widely used in domestic first-line cosmetics companies, and it has played a great role in preparing cosmetics with whitening, anti-aging and wrinkle removal functions.

　　From November 17th to 26th, the 21st Guangzhou International Automobile Exhibition will be held in Guangzhou China Import and Export Fair.

　　The exhibition area of auto parts and supplies, auto modification and new technology will be extended from November 17th to 20th. The 17th is Media Day, which is only open to domestic and foreign media and special guests. 18 -19 is the Professional Audience Day, with tickets to 100 yuan; 20 -26 is a public day, tickets for 50 yuan. This year’s exhibition will continue to use real-name registration system certification and swipe the ID card to enter the exhibition. Visitors can complete ticket purchase, ticket activation and real-name authentication at one time through the official WeChat of Guangzhou International Auto Show.

　　Following the opening of the newly-built Canton Fair Pavilion D in the last exhibition, this Guangzhou International Auto Show will continue to expand the use area of the Pavilion D, including six indoor exhibition halls and the outdoor exhibition area of the South Square in Zone D. At the same time, the newly-built "International Conference Center" was opened for the first time, with an exhibition scale of 220,000 square meters. There are 59 first cars in the world at this Guangzhou International Auto Show, including 8 first cars from multinational companies. 20 concept cars, including 9 international brand exhibition cars; There are 469 new energy vehicles, including 119 foreign brand exhibition vehicles, with a total of 1132 exhibition vehicles.

On December 9th, Shaanxi Provincial Public Resources Trading Center issued the "Publicity on the results of the proposed selection of pacemakers in the centralized procurement of pacemakers in provincial alliances (regions and corps)" (hereinafter referred to as "Publicity").

Review of pacemaker collection

Previously, several inter-provincial alliances have carried out the collection of pacemakers.

In 2019, Jiangsu Province launched the first domestic collection of pacemakers. The average price of this collection decreased by 15.86%, with the highest decrease of 38.18%. Among them, four of the five companies selected were imported, namely Medtronic, Abbott, Baiduoli and Boke, and only one domestic company was selected.

Since then, many provinces have also carried out the collection of pacemakers.

Up to now, the centralized purchase of pacemakers has covered three provinces (cities, districts) in 27 provinces, including Anhui, Jiangsu (two rounds have been carried out), Qinghai, Shandong, Fujian, Zhejiang (under planning), Qujing, Yunnan, Beijing-Tianjin-Hebei "3+N" and Shaanxi seven provinces and one corps, and only Shanghai, Hubei, Shanxi and Guangdong have no arrangements.

Judging from the existing collection results, the highest decline was the second round of cardiac pacemaker collection in Jiangsu Province in May this year, with a decrease of 69%. Although the Shaanxi Alliance has not announced the result of the decline, the average decline of the products to be selected is 57.77% and the highest decline is 78.26% based on the average price of 50,000-60,000 in the past.

Compared with coronary stents and artificial joints, the price reduction of cardiac pacemakers is very mild. This is not unrelated to the current market structure of pacemakers in China.

The domestic production rate is less than 5%, and it is too early to cut prices drastically.

At present, Medtronic, Abbott and Bocco account for 43.0%, 23.7% and 17.8% of the domestic pacemaker market respectively, and the three giants together account for 84.5% of the domestic market. Together with the second echelon’s Baiduoli and Sorin Group, the market share of imported pacemakers in China reaches 95.7%.

In recent years, the annual implantation of pacemakers has been increasing year after year, and the growth rate is maintained at around 10%. It is expected that about 100,000 pacemakers will be implanted in 2020, and the market scale will reach 4 billion yuan.

With the increasing demand in the market, a few imported enterprises occupy the vast majority of the market share. On the whole, China’s pacemaker market still belongs to the "seller’s market", and it is not realistic to achieve a substantial price reduction.

Looking back at the field of domestic pacemakers, the technology of local enterprises in China is still in the initial stage. If the price of centralized purchasing is too low, the market price of products will be reduced below the research and development cost. If there is no desirable benefit, who else is willing to face the difficulties and conduct independent research and development?

Moreover, unlike other conventional consumables, manual follow-up and maintenance services after implantation account for a large proportion in the cost of pacemakers. Pacemakers will be carried for life after being implanted in human body. Follow-up doctors need to put a special small computer probe on the skin and remotely check whether the pacing system works normally in vitro.

At present, China has not been able to establish a follow-up service technical team. If foreign-funded enterprises lose the election because of their varieties and their profits drop too much, they will change the existing service model and cut off the labor service costs such as follow-up, which will have a huge impact on patients. Based on the above considerations, the bargaining range of centralized mining needs to be more cautious.

Heyihui medical treatment viewpoint

Centralized purchasing is a "double-edged sword". How to use the "price-cutting knife" of the policy to realize the double benefits of price control and industry development is a difficult problem..

Since the beginning of centralized procurement, the fields of artificial joints and coronary stents have experienced an ultra-high decline of up to 80% and 90%, which once made the industry discouraged. At the same time, in the medical field where patients’ health is paramount, the chronic diseases in the bidding field such as "winning the bid at the lowest price" and "bad money driving out good money" are criticized by the industry.

No matter how centralized purchasing develops, its ultimate beneficiary should be the patients. Based on the characteristics of the medical industry, how to grasp the bargaining degree of centralized purchasing really tests the decision-makers’ understanding of the industry and also affects thousands of medical device enterprises.

Source: Heyihui Medical