Application of Rubidium in the Field of Medicine and Health

Lichun ZHAO Yucui LU Wenbin ZHANG Shilei DING Xiayun LIAO Jiaping PAN

Abstract With the continuous development of science and technology， the role of rare and precious metal resources in medical treatment， economy and strategy has become increasingly prominent. This paper reviewed the application research of rare precious metal rubidium （Rb） in the field of medicine and health， mainly including the application significance of Rb in the field of medical and health， typical applications and problems in the field of medicine and health， and the important research significance of the research and development of medicine.

Key words Rubidium; Health medicine; Development and application

Received： May 1 2021  Accepted： July  2021

Supported by National Talent Project of "Youth Qihuang Scholars" （2020）; High-level Innovation Team Project of Guangxi Colleges and Universities （2019-52）.

Lichun ZHAO（1980-）， male， P. R. China， researcher， PhD， devoted to research about chemical components and pharmacological activity of plants.

Yucui LU （1996-）， female， P. R. China， master， devoted to research about chemical components and pharmacological activity of plants.

#These authors distributed equally to this work.

*Corresponding author. E-mail： hyzlc@126.com.

Rubidium （Rb） is a rare alkali metal in the form of waxy solid with silver-white metallic luster and light， soft and ductile texture. It has an atomic number of 37， and is located in the fifth period of the periodic table， group IA， i.e.， the same group as Li， Na， K， and Cs. It has a lively chemical property[1-2]. At room temperature， Rb can ignite spontaneously in the air; and it reacts violently with water， even with ice below -100 ℃ to produce hydrogen and rubidium hydroxide[3-4]. Therefore， pure metal Rb is usually stored in sealed glass ampoules[5-6]. The content of Rb in the earths crust is about 0.009%， which ranks sixteenth in the contents of elements in the earths crust.

Rb vapor appears magenta at 180 ℃， and orange-yellow when it is higher than 250 ℃. Rb， as a typical dispersing element， often coexists with other alkali metal elements K， Na， Li， and Cs. Rb resources in nature are mainly distributed in salt lake brines and ores. At present， three independent Rb minerals have been discovered： rubidium microcline， Rb-rich borate-ramanite and rubidium mica-voloshinite[7]， but the reserves are small. People mainly develop and extract Rb from granite pegmatite deposits， and the main mineral raw materials are lepidolite and pollucite[8]. Internationally， the United States， South Africa， Namibia， Zambia and other countries are rich in Rb reserves， and lepidolite and pollucite in the sediments of Lake Baenic in Canada and Salar de atacama brine in Chile are especially rich in Rb resources[9]. Chinas Rb resources are also relatively rich， with reserves of about 184 000 t， mainly based on Rb oxide resources， accounting for 97% of the national Rb resources.

Chinas Rb resources are mainly found in lepidolite and salt lake brines. These minerals are widely distributed in China. For example， the niobium-tantalite minerals in Jiangxi and Henan contain a large amount of lepidolite， and the Zigong brine contains Rb， Li and Cs resources. Among them， the Rb content of lepidolite accounts for 55% of the countrys Rb resource reserves. Yichun， Jiangxi， has the most abundant reserves of lepidolite， and it is the main raw material for Chinas current Rb mineral products. Rb is also widely present in the form of soluble salts， such as salt lakes and underground brines in Qinghai， Tibet， Sichuan， Hubei and other places in China， with relatively low abundance and difficult development， which are a potential Rb resource in China. In addition， there are abundant Rb reserves in seawater， and total Rb reserves in seawater reach 190 billion t. These resources provide abundant raw materials for the comprehensive development and utilization of Rb and its compounds[10-11].

There are two natural isotopes of Rb， 85Rb and 87Rb， of which 87Rb is radioactive[12]. Rb is an essential trace element or micronutrient in the human body. It has very low toxicity to the human body and is mainly excreted through urine[13]. Rb and its compounds are widely used in glass， medicine， chemical industry， energy， electronics and other fields because of its strong chemical activity and excellent photoelectric properties. Since its discovery for more than 100 years， its role and value to humans have become increasingly prominent， and it has also been valued by researchers[14]. In 199 the Institute of Nutrition and food Hygiene， Chinese Academy of Preventive Medicine， calculated based on the intake and Rb content of various foods， the average intake of Rb per person in China （reference） was 3.41 mg/d. However， the Rb element in food exists in the form of complexed macromolecules， and the Rb-containing complexes are extremely stable and difficult to be absorbed by the human body. As a result， most of the Rb resources ingested through food will be excreted， causing the human body to lack the trace element Rb. In recent years， with the vigorous development of Rb resources in the world， the research on Rb in the medical and health field has increased， and how to promote the safe and efficient development of Rb in the medical and health field， and speed up the development of easily absorbed Rb-containing foods， has become a hotspot and focus of general attention and research in all countries in the world. Therefore， we briefly elaborated and summarized the research progress of Rb in the field of medicine and health at home and abroad in recent years.

The Discovery and Application of Rb

In the 1850s， German chemist Robert·Wilhelm·Bunsen invented a lamp that could burn gas and named it "Bunsen burner." When different substances are placed in the high-temperature flame of this kind of lamp， the flame will have different color changes： for example， when a substance containing sodium is placed， the flame will turn yellow， and when a substance containing potassium is placed， the flame will turn purple. With the help of the spectrometer developed by physicist Gustav·Robert·Kirchhoff， they successfully developed a method for reliably exploring and analyzing the composition of substances-spectroscopy. In 186 using this method， scientists discovered an unknown element that produces red spectral lines in a mineral water and lepidolite ore. This newly discovered element is named Rb after its spectral line color （in Latin， Rb means deep red）. The discovery of Rb was the first victory achieved by using spectroscopic analysis to study and analyze the elemental composition of matter[15].

As an important rare precious metal， Rb has strong chemical activity and excellent photoelectric effect performance， so it is called metal having "eyes". Rb metal is also regarded as a strategic new resource and has been highly valued by all countries. Rb has made great progress in traditional application fields such as electronic devices， catalysts， special glass， biochemistry and medicine， and also shows strong vitality in emerging applications such as magnetic fluid power generation， thermionic conversion power generation， ion propulsion engines， devices for converting laser energy to electrical energy， and cesium ion cloud communication[16].

The abundance of Rb in the earths crust ranks sixteenth， and the content is thousands of times that of Cs. It is a rare precious metal with relatively rich resources， which makes the development and application of Rb products have certain resource advantages[17]. In recent years， Chinas research on Rb has mainly focused on the extraction process of Rb， while ignoring the application research of Rb， which has seriously hindered the development of Chinas Rb industry and has made Chinas rich Rb resources underutilized. It is worth noting that some Rb-containing compounds have multiple properties and are not limited to one application field. Therefore， the vitality of Chinas Rb industry lies in exploring and developing the application range of Rb. For example， in the application of Rb in the medical and health field， we should first master its current application and explore its medicinal mechanism， and then expand its application range according to the mechanism and comprehensively improve the use value of Rb resources.

Typical applications of Rb in the medical field

Rb is an alkali metal element and has similar chemical properties to Li， Na， K and Cs. Therefore， it has similar biological functions as potassium， as well as unique neurophysiological functions， myocardial physiological functions and anti-cancer functions of Rb. Studies have shown that the occurrence， development and treatment of many diseases may be related to the state of Rb in the body[18]. Rb compounds such as rubidium chloride， rubidium iodide， rubidium radioisotopes， etc.， have been used in medicine to some extent. For example， rubidium chloride and several other Rb salts are often used as density gradient media in the ultracentrifugation process of DNA and RNA; radioactive Rb can be used for blood flow radioactive tracing[19-20]; and Rb salts are also commonly used to treat goiter， and can be used as an antimanic agent and mood stabilizer， and Rb iodide can be used to treat syphilis[21].

Wide application of Rb in medical imaging

The 82Rb positron emission computed tomography （82Rb PET/CT） imaging equipment， which uses Rb metal as an important material， can accurately evaluate the location and degree of coronary artery disease in addition to conventional X-ray imaging[22]. Rb can also be used as a tracer to detect damaged tissues and heart disease， with accurate imaging quality[23]. Gaudieri et al.[24] used hybrid （82Rb） PET/CT imaging to assess coronary artery fat thickness （PCFT）， coronary artery calcification （CAC） score， predictive value （CAD） of myocardial perfusion reserve （MPR）， and normal myocardial perfusion imaging （MPI） in patients with suspected coronary artery disease. 640 patients with 82Rb PET/CT MPI without obvious CAD， normal in resting pressure， were studied. PCFT is calculated on CT images as the maximum fat thickness （mm） between the surface of the heart and the visceral epicardium surrounding the main coronary arteries. The CAC score is divided into 0， <400 or ≥400. When < it is considered that MPR is lowered. The endpoint events are cardiogenic death， non-fatal myocardial infarction， and coronary revascularization. Through （82Rb） PET/CT imaging， it was found that in patients with suspected CAD and normal pressure MPI， the increased risk of the heart was related to coronary vascular dysfunction and high PCFT; and PCFT could help identify patients with a higher risk of events. It shows that the comprehensive assessment of anatomical and functional vascular abnormalities by 82Rb PET/CT imaging may be better for risk stratification.

Antimicrobial ability of Rb and its application in promoting the proliferation and differentiation of osteoblasts

Zadik et al.[25] applied Rb to the bucky ball （C-60） and changed the crystal structure to form an insulating， superconducting， and magnetic Jahn-Teller metal， which can change from insulation to superconducting after pressure is applied. Hydroxyapatite （HAp） is a widely used biological material because it is the main inorganic component of human bones and teeth. Liu et al.[26] successfully prepared Rb-doped nano-hydroxyapatite particles （Rb-nHAp） by hydrothermal method. X-ray diffraction （XRD）， scanning electron microscope （SEM）， transmission electron microscope （TEM）， X-ray photoelectron spectroscopy （XPS） and Fourier transform infrared spectroscopy （FT-IR） were used to characterize the structure and morphology of the sample. The XRD and FT-IR results of Rb-nHAp showed that the powder was pure HAp， had a good crystal structure， and no other phases or impurities. SEM and TEM observations showed that the Rb-nHAp powder had a uniform rod-like morphology with a size of 50-300 nm. In vitro results showed that on day 7 or longer， compared with pure HAp， 3% and 5% of Rb-nHAp enhanced the proliferation and differentiation of MG-63 cells. In vitro bacterial proliferation test showed that Rb-nHAp powder had a high inhibitory effect on both bacteria. In short， doping with Rb can simultaneously endow nano-hydroxyapatite （nHAp） with good cell compatibility and antibacterial ability. It shows that Rb-nHAp may be a promising material for biomedical applications.

In order to give titanium-based metal materials excellent biological activity and antibacterial functions at the same time， Manke Chen et al.[27] prepared a Rb-doped titanium surface by alkali-heat treatment， hydrothermal treatment and heat treatment. An amorphous sodium titanate hydrogel layer was produced on a titanium substrate by alkali-heat treatment， and then crystalline rubidium titanate and sodium titanate were obtained on the titanium surface by hydrothermal method and heat treatment. For a short period （day 1） on the Rb-doped titanium surface， the viability of MC3T3-E1 cells was inhibited. Over time （day 5）， its Rb-doped surface activity was comparable to that of alkaline phosphatase （ALP）. With the further extension of time （day 10）， it was found that the synthesis of collagen on the surface of Rb-doped titanium and the mineralization of osteoblasts in vitro were significantly enhanced. The surface of titanium doped with Rb showed antibacterial activity against Staphylococcus aureus at 12 and 24 h. The results showed that doping Rb on the titanium surface could simultaneously endow the material with good osteogenesis and antibacterial capabilities.

Aneeba et al.[28] used slow evaporation to grow L-lysine mono-salt and rubidium chloride-doped L-lysine mono-salt crystals， and compared the optical， mechanical and antifungal properties of the two. Single crystal X-ray diffraction （XRD） confirmed that the crystal was a monoclinic system， and the crystal growth had smaller grain boundaries. FTIR and EDX confirmed the functional group and existence of Rb. The grown crystal exhibited better transmittance than pure crystal in the ultraviolet-visible region， and the band gaps of pure crystal and doped crystal were 5.30 and 5.94 eV， respectively. The results showed that the doping of RbCl significantly improved the mechanical properties of the doped crystal， laying a foundation for the preparation of the device. The non-linear optical properties of the grown crystals all exceeded KDP， which was confirmed by Kurtz Perry technology. It suggests that the inhibitory effect of Rb crystals on Candida albicans， Candida parafilamentous， Aspergillus flavus and other pathogenic fungi is significantly stronger than that of pure L-LMHCL crystals.

Lichun ZHAO et al. Application of Rubidium in the Field of Medicine and Health

The application of Rb in the modification of biological materials

Tan et al.[29] studied the effects of Rb element on the phase composition， microstructure， mechanical properties and cell response of CaO-SiO2-Na2O-B2O3-MgO-ZnO-P2O5 system of bioglass ceramics， and designed the composition of the glass ceramics with and without Rb. The results showed that the crystalline phases of hydroxyapatite （HA） and Mg-pyrophosphorite （Ca18Mg2H2（PO4）14） were formed in the bioglass ceramic matrix without Rb; and after the addition of Rb， only the HA phase was detected. After adding Rb， the crystal grain size of the crystals in the bioglass ceramics increases. Adding Rb can improve the flexural strength of bioglass ceramics. After adding Rb， the crystal grain size of the crystals in the bioglass ceramics increased. Adding Rb could improve the flexural strength of bioglass ceramics. Cell test results showed that Rb-containing bioglass ceramics had better cell adhesion， proliferation and alkaline phosphatase （ALP） activity. In short， Rb-containing glass ceramics have good mechanical properties， excellent biological activity and biocompatibility， and are expected to be used in the field of medical bone regeneration.

Xiang et al.[30] studied the mesoporous bioactive glass scaffolds containing Rb to support angiogenesis， osteogenesis and antibacterial activity， and found that Rb-containing mesoporous bioglass （Rb-MBG） scaffolds were formed by the effects of adding Rb on the angiogenesis and osteogenic differentiation of hBMSC. The experiment characterized the phase composition， microstructure， pore size distribution， ion release， biological activity， drug loading ratio and release rate of Rb-MBG. The proliferation and differentiation of hBMSC， the markers of bone formation （ALP， COL-1） and angiogenesis （VEGF， HIF-1α）， and wnt/β-catenin-related signaling pathway genes were studied through cell culture. Rb-MBG loaded with the antibacterial agent enoxacin （ENX）， Escherichia coli and S. aureus were cultured together to study its antibacterial effect. The results showed that the sample had a macropore structure of 350-550 μm and a mesopore size of 4.5-5.5 nm; the addition of Rb could increase the ALP activity of hBMSCs， the secretion of VEGF and COLI， and the expression of HIF-1α; Rb-containing MBG might enhance the proliferation and differentiation of hBMSC through the effect of Wnt/β-catenin signaling pathway; and Rb-MBG scaffolds could effectively load and continuously release Rb ions and ENX， thereby synergistically destroying bacterial cell membranes， and achieving antibacterial effects. In conclusion， adding Rb to MBG can improve the angiogenesis and osteogenic differentiation of hBMSCs， as well as the antibacterial activity.

Antidepressant effects of Rb

Depression is a dysfunction of the central nervous system. Rb has a high tolerance and has been used clinically as an antidepressant for decades. Since the 1960s， due to the widespread use of Li in psychiatric clinics， people have also conducted in-depth research on the Rb element of the same group of Li[31]. In 1969， Meltzer proved for the first time that Rb has an excitatory effect on rhesus monkeys[32]. In 1970， Stolk et al.[33] demonstrated that Rb could enhance the transport of NE after the inhibition of norepinephrine （NE） biosynthesis in the rat brain. After receiving RbCl， the prevalence frequency of EEG in monkeys shifted higher， and the activity behavior increased. After continuous administration of Rb， the utilization of NE increased after the synthesis of norepinephrine in the brains was inhibited， the disappearance rate of NE in the brainstem was accelerated， and the release of active NE was also accelerated. These behaviors of Rb are just the opposite of the ability of Li to slow down the EEG and lower the activity， so it has been used to treat depression[34]. The clinical results of using Rb as a drug for treating depression found that after 4 weeks of RbCl drug treatment， 70% of patients with refractory depression had a significant effect and no serious adverse reactions[35]. Calandra et al.[36] used RbCl （540 mg/d） or clomipramine （100 mg/d） in a double-blind study of 28 patients with depression for 30 d. The results showed that the antidepressant effect of RbCl was better than clomipramine， and there was no serious adverse reaction; and its effective plasma Rb concentration was 0.10-0.32 mmol/L.

The application of Rb against cancer and neurological diseases

Chen et al.[37] studied the relationship between the addition of RbCl and the composition of the fecal microbiome in order to further understand the mechanism of Rb against cancer and neurological diseases from the perspective of the fecal microbial community. The characteristics and bacterial microbiome changes of 51 mice treated with RbCl and 13 untreated mice were evaluated. Sequencing of the 16 S ribosomal RNA gene of the fecal microbiota showed that RbCl maintained the diversity of the fecal microbial community as a whole， while the fecal microbial composition changed significantly after RbCl exposure. RbCl significantly increased Alpelisib and Clostridium， decreased the abundance of sulfate bacteria （including Deltaproteobacteria， Desulfovibrio nales， Desulfovibrionaceae， and Desulfovibrio）， and significantly inhibited the abundance of Tenericutes， Mollicutaceae， linear moneron， anaerobic nematodes and nuclear-free nematodes. Regarding archaea， they only observed two less affluent archaea Sulfolobus and Acidiplasma at the genus level. Experimental results indicate that changes in fecal microbes may partially contribute to the anticancer or antidepressant effects of RbCl. These findings further confirm that the microbiome may be a target for therapeutic intervention.

The application of Rb in anti-epilepsy

RbCl is also used clinically as an antiepileptic drug. At present， some scholars believe that compared with Li， nitric oxide and glutamate are contributors to the antiepileptic activity of rubidium chloride. Researchers evaluated and compared the effects of RbCl and lithium chloride （LiCl） on different epileptic seizure patterns in mice， and determined the involvement of NMDA receptors and the nitrification pathway. In order to evaluate the seizure threshold， the animals received intravenous pententetrazole （PTZ， 0.5%; 1 ml/min）. Male NMRI mice （6-8 weeks） received intraperitoneal （i.p.） injections of different doses of RbCl and LiCl. A dose of RbCl greater than 10 mg/kg showed significant anticonvulsant activity 60 min after administration. The anticonvulsant effect of LiCl was greater than 5 mg/kg and lasted for 30 min at the threshold of seizure induced by PTZ. However， RbCl （10， 20 mg/kg， ip） or LiCl （5， 10 mg/kg， ip） injections did not induce epileptic seizure model induced by protection against the maximum electric shock （MES） or the lethal dose of PTZ （80 mg/kg） by intraperitoneal injection. Using L-NAME （non-selective nitric oxide synthase （NOS） inhibitor， 10 mg/kg; ip） and 7-nitroindazole （selective neuronal NOS inhibitor， 30 mg/kg; ip） in the PTZ-induced seizure threshold model for pretreatment could enhance the anticonvulsant effects of RbCl （5 mg/kg， ip） and LiCl （1 mg/kg， ip）. Injection of MK-801 （NMDA receptor antagonist， 0.05 mg/kg; ip） before RbCl （5 mg/kg， ip; P<0.001） and LiCl （1 mg/kg， ip; P<0.001） could increase anti-seizure activity. However， treatment with L-arginine （precursor of nitric oxide， 100 mg/kg; intraperitoneal） reduced RbCl （20 mg/kg， intraperitoneal; P<0.001） and LiCl （10 mg/kg， intraperitoneal; P<0.001） seizure thresholds.  The measurement of nitrite levels in the hippocampus of animals showed a significant decrease after treatment with RbCl （20 mg/kg， i.p; P<0.05） and LiCl （10 mg/kg， i.p; P<0.01）. It indicates that RbCl may protect the central nervous system in the PTZ-induced seizure threshold model from the effects of seizures through the NMDA/nitrater pathway （similar to the role of lithium in mice）[38].

Not only that， Rb is also an essential trace element for the human body[39]. Rb is ubiquitous in nature and exists in animals and plants at certain concentrations. The concentration of Rb in human tissues remains unchanged or decreases with human aging， and can stimulate or promote growth[40]. In terms of metabolism in the body， scientists have discovered that there may be a balance and regulation mechanism of Rb， and it can supply newborns through the placenta and breast barriers[41]. Experimental studies have found that Rb can not only affect growth， reproductive function， brain development and brain aging[42]. Anke et al.[43] studied the effects of Rb on growth and reproduction. They found that compared with goats fed with Rb at 1 or 10 mg/kg， the feed intake of goats fed with feed containing Rb less than 0.28 mg/kg decreased， resulting in reduced their growth rate and increased rate of spontaneous abortion. In terms of food intake， young goats who lacked Rb during growth and pregnancy consumed an average of 23% more food than the control group， but the food intake during lactation was significantly lower than that of the control group. During the sterile period， pregnancy and lactation， the Rb-deficient aged goats consumed 41%， 14% and 24% less food than the control group， respectively. These facts indicate that after the Rb stored in the body is exhausted， the lack of Rb will have a significant impact on the food intake and function of goats. Meanwhile， in medicine， Rb is also often used to treat other diseases such as the nervous system， cardiovascular system， urinary system， and senile cataract[44-46].

Problems faced by Rb in the application of medicine and health

At present， the application of Rb in the field of medicine and health is still in its infancy. There is still a large distance to the wide range of applications， and the following problems need to be solved urgently.

Difficulties in mining， high product prices

Due to many challenges facing the development of Rb， the current global demand for Rb is not high and it is difficult to use in daily life. Therefore， it is difficult for people to feel its importance in daily life. At present， Rb resources are in an awkward situation of "production-sales" dilemma. The main reason is not because the resources of Rb metal are not abundant， nor because it is not widely used， but because its high mining， purification and production prices lead to a low demand. According to the data of the US Geological Survey： in 2010， the price of Rb with a purity of 99.75% was approximately US$52.33/g[47]. Excessive prices will cause consumers to use other alternatives. However， with the continuous research on the separation and extraction technology of Rb， scientists have successfully reduced the apparent activation energy of the alkaline leaching reaction to 37.41 kJ/mol， realizing the efficient leaching of Rb[48].

Aiming at the characteristics of a Rb mine in Gansu that Rb-containing mica has weak magnetic properties and there are less iron-containing minerals in gangue minerals， Chen et al.[49] developed a strong magnetic-flotation combined process to recover Rb in minerals， concentrated Rb-containing muscovite in the ore by strong magnetic separation， improved the grade of Rb in the coarse concentrate by flotation， and reclaimed tantalum and niobium by gravity separation， obtaining Rb concentrate with mica content close to 90%. The grade of Rb2O was 0.610%， the recovery rate was 26.81%， and the comprehensive recovery rate of Rb in mica reached 92.55%. In addition， the flotation tailings were gravity-selected to comprehensively recover tantalum and niobium， and the recovery rate of tantalum and niobium was 33.64%. It is believed that in the near future， through the unremitting efforts of researchers in the development of Rb resources， the price of Rb will gradually decrease and the demand will also increase. In the long run， the application of Rb in the medical and health field will inevitably become more and more extensive.

Research on the human body mechanism of Rb is not in-depth

At present， it is known that the physiological and biological functions of Rb are similar to that of K， but the research on its neurophysiological function， anti-cancer function， and related pharmacokinetics， pharmacology and medicinal mechanism and its clinical research are not in-depth enough， bringing difficulties to how to expand the application of Rb in the medical and health field. Therefore， speeding up the research on the medical mechanism of Rb and increasing the practical application of Rb in the medical and health field is an arduous task for the majority of medical and scientific researchers. China is rich in Rb resources， and although the medical community has begun to observe and study its physiological and biological effects， its breadth and depth are limited.

Although the only research data on Rb treatment has not found serious adverse reactions， in view of the long biological half-life of Rb， we should still be alert to the potential danger of Rb poisoning[50]. Studies have found that Rb can partially replace potassium. In animal experiments， the use of Rb to replace less than 30% of the bodys K would not produce any toxicity， the replacement of 25% to 29% of K in the brain and muscle would not be fatal， and the complete replacement of K with Rb could still maintain a few weeks of life. Human oral administration of RbCl instead of 10% to 15% of the bodys K does not have any toxic effects[51]. However， for patients who have been treated with Rb for a long time， studies on toxicity are still lacking. Therefore， it is necessary to establish rigorous medical monitoring and theoretical research.

Rb storage research still needs to be strengthened

Rb metal is chemically active， can ignite spontaneously in the air， and also reacts violently with water. Therefore， liquid paraffin， inert gas or vacuum conditions must be used to isolate the air in its production， storage and transportation. However， such nearly harsh storage method also greatly restricts the development and application of Rb in the medical and health field[52]. Metal Rb and oxide require special containers， and borosilicate glass ampere flasks can be used when the quantity is less than 100 g; and for larger quantities， stainless steel containers are more convenient for safe operation. Both are sealed， and the containers can be protected by vacuum or inert gas. Rb metal can also be handled and stored in an anhydrous saturated hydrocarbon liquid in a suitable container. During transportation， the ampoules are protected in aluminum foil rolls. Rolled ampule bottles or stainless steel vessels are packed in metal cans and filled with expanded frog stones， etc.， as fire protection and for resisting mechanical shock. Rb compounds must also be carefully managed and transported. Although the compounds are not as active as metals， they must be stored and transported in sealed polyethylene containers. Salts that are easy to absorb moisture must be stored in a dry place， and the containers are packed in metal cans and filled with expanded frog stones or foamed plastics[53-55].

The development direction of Rb in the pharmaceutical industry

As a strategic emerging mining resource， Rb has received great attention and has broad development prospects in the field of medicine and health. Mineral resources are the material basis for the development of strategic emerging industries. In order to promote the transition of Chinas economy to high-quality development， the strategic emerging industry Rb has become an inevitable choice.

Speeding up the protection and development of Rb resources

It is necessary to steadily advance the protection and development of Chinas rare and scarce mineral resources Rb and the development of the medical industry， and make planning to rationally develop and scientific use Rb ores. First of all， the separation and extraction technology must be continuously optimized and improved to improve the quality of Rb and its materials， reduce production costs， increase production， stimulate the research and development of Rb in the field of medicine and health， and promote the transformation and upgrading of Rb in Chinas pharmaceutical industry and the formation of new industries， so as to keep Chinas Rb resource application research at the worlds advanced level.

Strengthening the medical research and application development of Rb

Aiming at the current application dilemma of Rb in the medical and health field， we should promote the application of Rb in the medical and health field in the future. The pharmacokinetics， pharmacology， medicinal mechanism and clinical research of Rb should be strengthened and deepened. A kind of Rb drug needs to undergo repeated clinical trials before it is promoted. It may take several years or even longer to research and experiment. Once successful， it will promote the practical application of Rb in the medical and health field.

Conclusions

As an emerging resource， Rb has received increasing attention， especially its application in the medical and health field， which is of great significance for improving its resource utilization value. Rb reserves are huge， but it is difficult to separate and purify， and the medicinal value of single use still needs further study. Therefore， we summarized the development focus of Rb resources in the future. First of all， the optimization and improvement of separation and extraction technology and the increase of production capacity greatly stimulate the research and development of Rb in the medical and health field. Secondly， in view of the application dilemma of Rb in the medical field， it is necessary to strengthen medical research and promote the practical application of Rb in the medical and health field. Finally， attention should be paid to the application and development of Rb materials in the field of medicine and health. The special effects of Rb in diabetes， Parkinsons and cardiovascular diseases are worthy of in-depth study， so as to clarify the focus of the future development of Chinas Rb industry and develop characteristic Rb drugs or foods. To sum up， Rb is not as well-known as lithium， nor is it found everywhere like K and Na， but it is closely related to our lives—from its first appearance in the 1960s to its current essential role in various fields. In the future development of medicine， Rb resources will surely like spring breeze which blow thousands of pear trees to bloom overnight. It will surely enter peoples lives and create endless value for human health.

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