In recent years, membrane technology has rapidly “brought” in the pharmaceutical industry

From September 13th to 15th, a wonderful "big show" was staged at the Beijing International Exhibition Center. Its protagonist was "membrane technology." At the 2006 China International Film Industry Exhibition held by the China Petroleum and Chemical Industry Association and the China Film Industry Association, more than 100 film and technology companies from home and abroad gathered at the exhibition, and visitors were in an endless stream. The reporter saw at the exhibition site a number of new membrane technologies and equipment specially developed for pharmaceutical production developed by companies. Experts told reporters that in recent years, with the continuous improvement of drug quality requirements and the need to reduce production costs, membrane technologies such as ultrafiltration technology, pervaporation, and membrane distillation have rapidly become hot spots in the field of medicine. They are used to solve the problem of pharmaceutical production. The integrated engineering technology problems of extraction, separation, concentration, and purification provide guarantees and lay the foundation for improving the overall level of pharmaceutical production.

Ultrafiltration: Significant progress in application

It is understood that ultrafiltration technology has made remarkable progress in the field of medicine in recent years and has solved some technical problems well. For example, the problem of depyrogenation commonly encountered by manufacturers of pharmaceutical preparations, the previous method is generally repeated adsorption of activated carbon, but this method is labor-intensive, large loss and low yield; ultrafiltration membrane with less than pyrogen molecular weight is used to intercept the pyrogen, The labor intensity is small, and the product yield is high and the quality is good.

At the exhibition site, the reporter interviewed Yan Yanbin, an associate professor at Beijing Forestry University. He has been engaged in membrane technology research for 11 years. According to him, since the molecular weight of active ingredients (such as flavonoids, alkaloids, and total glycosides, etc.) is more than 1,000, ultrafiltration is very suitable for the depyrogenation of injections. Research on the depyrogenation process of Qingkailing injection by pharmaceutical companies of Beijing University of Traditional Chinese Medicine shows that the ultrafiltration method has higher baicalin content than activated charcoal adsorption products, and the product has a lighter color and a smaller number of particles. They used ultrafiltration membranes to filter the pyrogens in Chuan Shen Tong injection, Guan Shu injection, Song Mei Le injection and large infusion, and the liquid medicines can meet the requirements of the “Chinese Pharmacopoeia”. The Chinese Academy of Pharmacy of the Air Force Beijing Hospital used ultrafiltration to prepare three kinds of compound Chinese herbal injections: Salvia miltiorrhiza, Yinzhihua, and Shengmai. The resulting product has good clarity, and no sedimentation occurs after 3 months of placement, and the ultrafiltration depyrogenation can be effective. The land protects the loss of the active ingredients in the original formula.

Currently, ultrafiltration systems have also been used for the filtration of antibiotics such as erythromycin, penicillin, cephalosporins, tetracycline, lincomycin, gentamycin, rifamycin, etc.: Merck has used cutoffs in the United States. The ultrafiltration membrane with a molecular weight of 24,000 filters the cephalosporin fermentation broth, which leads to a 2% increase in yield over the use of a vacuum filter with a filter aid layer, reaching 98%, a reduction in material costs of 2/3, and equipment investment costs. Reduced by 20%; ultrafiltration membranes can effectively process cephalosporin C fermentation broth without blocking or fouling the membrane, increasing recovery, making the concentration of cephalosporin C in the concentrate much lower than that of the original broth. Higher; some penicillin manufacturers use ultrafiltration to remove fermentation by-products and residues as well as some soluble proteins, changing the previously required method of adding more toxic and expensive demulsifiers, making the process simple and quick. In addition, in the process of producing vitamin C by fermentation, Chinese researchers have used Sun-flo ultrafiltration membrane system instead of heat precipitation to remove impurities such as mycelia, proteins and suspended particles remaining in the fermentation broth, eliminating the need for pretreatment, Heating, centrifugation and other processes save energy consumption and increase the yield of cologne acid.

Associate Professor Yan Bin also told reporters that macromolecules are mostly thermally unstable, and ultrafiltration has the property of rapid filtration at low temperatures, which has become an important means for the refinement of such drugs. The production practice shows that the concentration of phytase fermentation broth can be concentrated by using a PS tube ultrafiltration membrane system with a molecular weight cut off of 20,000. The concentration factor can be up to 6.53 times, the concentration can reach 99.99%, and the rejection rate can reach 99.93%. Utilizing PAN ultrafiltration Membrane was purified and purified from the blood of Tibetan yak cattle. The average specific activity of thrombin obtained was 38.24 IU/mg, which was twice that of the product obtained by traditional methods.

In addition, ultrafiltration is used for the separate separation of traditional Chinese medicine macromolecular compounds and is increasingly accepted by companies.

For example, Banlangen tea and Banlangen granules were traditionally prepared by water extraction and alcohol precipitation. They have the disadvantages of high production cost, long period, and poor safety. The PS ultrafiltration membrane with a molecular weight cut off of 50,000 was used instead of alcohol precipitation to treat Banlangen water. The liquid can make the extraction process efficient and energy-saving; the molecular weight of Tremella Polysaccharides is approximately 70,000. The use of CA ultrafiltration membrane to concentrate the Tremella dollar extract can increase the product yield by 22.4% compared with the conventional concentration method and shorten the concentration time. Fiber ultrafiltration membrane can also be used to extract active polysaccharides from Liuwei Dihuang Decoction. The process is simple and the production cycle is short.

Pervaporation: outstanding energy-saving advantages

It is understood that in the last two years, a new membrane separation technology based on the difference of the dissolving and diffusing properties of components in liquid mixtures, using dense polymer membranes to achieve separation of components - pervaporation technology has been gradually used in pharmaceutical and chemical fields. Trace water removal and wastewater treatment. At present, many domestic companies have introduced this technology. For example, Harbin Pharmaceutical Factory completed and put into operation 3,000 tons/year of ethanol solvent dehydration and reuse in the second half of 2004. Shenyang Dongrui Science & Technology Co., Ltd. put into operation 5,000 tons/year in September 2005. In the ethanol dehydration project, a company in Shandong put into operation a 3,000-ton/year t-butanol industrial dewatering device in December 2005. This technology brings obvious economic benefits to the company.

Associate Professor Yan Bin introduced that in the pervaporation process, due to the selective passage of some components in the liquid to the membrane, the molecules of the easily-permeable constituents are dissolved and adsorbed on the surface of the membrane and preferentially diffuse under the action of the chemical gradient of the membrane. As a result, the composition of the feed liquid on the upstream side is changed, and the components penetrating to the lower side through the polymer membrane are vaporized on the membrane surface due to the partial pressure of vapor smaller than the saturated vapor pressure thereof, and then the condensate system is condensed to form a permeate product. Pervaporation technology can achieve liquid separation tasks such as distillation, extraction, and absorption that are difficult to accomplish by conventional methods such as distillation, separation of near-boiling point, constant-boiling point mixtures, and isomers, which are difficult to separate or cannot be separated by distillation.

Compared with the traditional separation technology, the characteristics of the pervaporation process: First, efficient, select the appropriate membrane, single-stage can achieve a high degree of separation; Second, low energy consumption, generally saving energy than azeotropic distillation 1 / 2 ~ 1/3; Third, the process is simple, additional processing is less, easy to operate; Fourth, do not introduce other reagents in the entire process, so the product and the environment will not be contaminated; Fifth, to facilitate amplification and coupling and integration with other processes . At present, the pervaporation dehydration technology is mainly used for dehydration treatment of alcohols, ketones, aromatic compounds, amines, esters, ethers, organic acids, nitriles, aliphatic hydrocarbons, and organosilicon compounds. Since many active ingredients of traditional Chinese medicines (such as total emodins, flavonoids, chlorogenic acid, loganin, astragaloside, etc.) are leached or precipitated with alcohols, alcohols need to be recycled, and pervaporation technology is needed. The purpose of recycling can be achieved simply and quickly.

Membrane Distillation: High Concentration at Low Temperature

At the exhibition site, some companies also demonstrated new membrane distillation equipment. It is understood that membrane distillation is a technique that uses a hydrophobic microporous membrane to separate two aqueous solutions of different temperatures. Under the influence of the difference in vapor pressure on both sides of the membrane, the hot side steam enters the cold side through the membrane hole and condenses on the cold side. Membrane distillation is the same as evaporation-transfer-condensation in conventional distillation. Both are based on gas-liquid equilibrium and require latent heat of vaporization to achieve phase change. Compared with the conventional separation process, the advantage of membrane distillation is theoretically 100% separation of ions, macromolecules, colloids, cells and other non-volatile substances; the operating temperature is lower than the traditional distillation process; the operating pressure is lower than the process; Low performance requirements; suitable for the separation of special substances, and can separate very high concentrations of substances, and can even produce crystallization; high efficiency.

Since the membrane distillation technology has the characteristics of low-temperature concentration, it can be used for the concentration of heat-sensitive substances. For example, the traditional extraction method of penicillin is solvent extraction, and the process is complicated. However, direct contact membrane distillation is used to condense the penicillin aqueous solution and the concentration process is relatively stable. Motherwort and Radix Paeoniae Rubra are commonly used traditional Chinese medicines, and the two indicators are stachydrine and paeoniflorin. All of them are water-soluble and have a boiling point higher than that of water. The vacuum membrane distillation method is used to concentrate the motherwort and the red peony extract. The efficiency is high, the energy consumption is small, and the operation is convenient. The rejection rate of the active ingredient is almost 100%.

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