Concentrated biopharmaceutical preparations

Biopharmaceutical concentration and extraction

1 Application industry products

●amino acid

●antibiotics

●enzyme preparation

●Concentrated extraction of traditional Chinese medicine preparations

II Amino acid process description

Amino acids are the basic units that make up proteins. Currently, there are five production methods, including direct fermentation, precursor fermentation, enzymatic fermentation, chemical synthesis, and protein hydrolysis extraction. Both direct fermentation and precursor fermentation are commonly referred to as fermentation methods, and most amino acids are produced using fermentation methods. Fermentation broth is an extremely complex multiphase system, containing microbial cells, metabolites, unused culture medium, etc. Sometimes impurity amino acids have chemical structures and physicochemical properties that are very similar to the target amino acids. These all determine that the downstream processing of amino acid fermentation broth requires a series of engineering unit operations. The characteristics of Kaimo amino acid membrane integration process are:

1. Operating at room temperature, the material has no phase change, high separation accuracy, clear and transparent permeate, low impurity content, greatly reducing the load of subsequent refining processes;

2. Realize high fold concentration of fermentation broth, with no retention of active ingredients in the fermentation broth, and improve product yield;

3. No filter aid is required during the treatment process, achieving clean production, reducing the amount of acid, alkali, and water washing, improving the biodegradability of wastewater, and reducing environmental costs;

4. Ceramic film has strong anti pollution ability, long service life for acid and alkali cleaning, and can recover bacterial cells from fermentation broth, bringing more profit points to enterprises;

5. PLCControl by upper computer, monitoring process parameters by upper computer, reasonable setting to reduce energy consumption, remote and on-site operation, reducing labor intensity;

III Antibiotic Process Description

Antibiotics have a relative molecular weight ranging from 300 to 1200 and exist in liquids. Antibiotics are mainly classified into five categories: β - lactam antibiotics (such as penicillin), amino acid glycoside antibiotics, macrolide antibiotics (such as erythromycin and streptomycin), tetracycline antibiotics (such as tetracycline), and peptide antibiotics (such as vancomycin). The main methods for extracting from fermentation broth include adsorption, solvent extraction, ion exchange, and precipitation. However, these processes are often complex, time-consuming, and require a large amount of raw materials during the extraction process. Energy consumption is high, and antibiotics are prone to deactivation during the long extraction process. The product recovery rate is low, and the wastewater pollution is severe and difficult to treat. The concentration of antibiotics in the obtained solution is often very low. Our membrane separation, concentration, purification and purification technology is used for clarification, concentration, desalination of antibiotic fermentation broth and concentration recovery of antibiotics in waste liquid. It has the following characteristics:

1. Operating at room temperature, the material has no phase change, high separation accuracy, clear and transparent permeate, low impurity content, greatly reducing the load of subsequent refining processes;

2. Suitable for the separation, concentration, and purification of thermosensitive substances (such as drugs, fruits, enzymes, etc.) to improve product yield;

3. It can achieve high fold concentration and significantly improve product yield (5-12%) compared to traditional processes. The concentrated bacterial cells can be recycled as feed;

4. No filter aid is required during the treatment process, achieving clean production, reducing the amount of acid, alkali, and water washing, improving the biodegradability of wastewater, and reducing environmental costs;

5. Asymmetric membrane pore size distribution, not easily contaminated, can maintain long-term stable filtration at high flux, while complying with GMP specifications;

6. Ceramic membranes, ultrafiltration membranes, and nanofiltration membranes are resistant to pollution, acid and alkali cleaning, and have a long service life. They recover bacterial cells from fermentation broth, bringing profit points to enterprises;

7. PLCControl by upper computer, monitoring process parameters by upper computer, reasonable setting to reduce energy consumption, remote and on-site operation, reducing labor intensity;

4 Process description of biological plum preparation

In the enzyme preparation industry, the refining process of enzymes mainly includes two aspects: the separation of bacteria (including fermentation residue) from the enzyme fermentation broth, and the concentration and purification of the enzyme clear liquid. The traditional production process involves fermentation, coagulation and precipitation, filtration, solvent extraction, vacuum evaporation, and drying, which result in high energy consumption, high enzyme inactivation rate, and low yield. In the past decade, membrane separation technology has been successfully used in the production of liquid enzyme preparations for separation, concentration, and purification, achieving good benefits.

The use of ceramic membrane microfiltration technology enables the process to collect a high concentration of live bacterial cells in a very short period of time, and the live bacterial cells are basically not deactivated, greatly improving the competitiveness of the product and greatly increasing the yield of the product, ensuring the high profit of the enterprise to the greatest extent. At the same time, ceramic membrane filtration is not only a high interception of the physical state of live bacterial cells, but also fully separates the enzyme downstream clear liquid with high clarity, reducing the production load of downstream concentration processes and playing a role in protecting downstream membrane processes.

The downstream enzyme clear solution is concentrated by ultrafiltration, which simultaneously removes some pigments, impurities, and most inorganic salts during the ultrafiltration process, greatly improving the quality and stability of the product. At the same time, ultrafiltration concentration is carried out at room temperature, with no loss of enzyme activity and high yield. In addition, the membrane system is easy to operate, greatly reducing labor intensity and shortening the concentration time. The wastewater discharge from ultrafiltration systems is minimal, which to some extent reduces environmental pressure. In summary, the use of ceramic membrane microfiltration series ultrafiltration concentration process in this enzyme process has advantages that traditional processes cannot compare with. The membrane system not only has high product quality and yield, but also has low energy consumption, low production cost, and short production cycle. And these are precisely the indispensable factors for the continuous development of enterprises, so membrane technology has a vast application space in enzyme manufacturers.

Micro filtration replaces centrifugal filtration and filter media layer filters

5 Concentrated extraction of traditional Chinese medicine preparations

Traditional Chinese medicine pharmaceuticals generally include extraction, concentration, purification, drying, and formulation. The concentration of extraction solution in the process is one of the key unit operations in modern traditional Chinese medicine pharmaceuticals. The concentration system of extraction solution is very complex, with many impurities (such as tannins, proteins, gums, sugars, and resins), high temperature, long time, and loss of effective and volatile components. Conventional suspension freeze concentration, progressive freeze concentration, natural external circulation two-phase flow concentration, online anti hanging wall three-phase flow concentration, macroporous adsorption resin separation concentration, etc. are difficult to achieve high relative density quality requirements, and there are also problems such as equipment scaling and waste liquid discharge.

Guangzhou Kai Membrane Filtration Equipment Co., Ltd. has developed membrane concentration and extraction processes (reverse osmosis, nanofiltration, ultrafiltration and microfiltration, membrane distillation and osmotic distillation, etc.) based on traditional techniques, which are suitable for the concentration, separation and extraction of traditional Chinese medicine extracts. The concentration process of the new technology operates at room temperature, without phase change, and the thermosensitive components are protected, while the aromatic components are maintained. At the same time, the equipment scale is small, the energy consumption is low, and the separation efficiency is high. The main membrane separation process principles are as follows.

1. Membrane permeation

Membrane permeation is a process that uses pressure as a mass transfer driving force to separate and concentrate substances through membranes. It is divided into several filtration processes, such as reverse osmosis, nanofiltration, ultrafiltration, and microfiltration. The microfiltration process in graded filtration uses high-temperature resistant ceramic membranes for direct filtration without the need for cooling. Temperature control is crucial for subsequent ultrafiltration, nanofiltration, and reverse osmosis membrane concentration. Excessive temperature not only affects concentration efficiency but also shortens the membrane's service life. The suitable temperature range is 1-45 ℃. The cleanliness of the membrane is an important factor in ensuring work efficiency and service life. Therefore, the pretreatment of the concentrated solution is crucial. The process uses multi-stage membrane permeation concentration with different pore sizes to solve problems such as low concentration factor, work efficiency, and service life. Since the 1980s, membrane permeation has been widely concentrated in the concentration of fruit and vegetable juices such as apples, grapes, and tomatoes, similar to the principle of traditional Chinese medicine extraction, and therefore has broad application prospects.

2. Membrane distillation

Membrane distillation is a newly developed membrane concentration process in the 1980s, which uses the pressure difference of water vapor caused by the temperature difference on both sides of a hydrophobic microporous membrane as a mass transfer driving force. Compared with other membrane separation methods, membrane distillation can achieve higher separation capacity and less membrane blockage at low temperature and pressure. It has broad application prospects in concentrating thermosensitive and high osmotic pressure solutions. Membrane distillation can be divided into direct contact membrane distillation, air gap membrane distillation, sweep gas membrane distillation, vacuum membrane distillation, permeable membrane distillation, etc.

3. Osmotic distillation

Permeation distillation is also a recently developed membrane separation process similar to membrane distillation. This process involves adding a penetrant, such as a saturated saline solution, to the pure water side of a hydrophobic microporous membrane to achieve a much higher osmotic pressure than the solution to be concentrated. From the perspective of mass transfer, the dehydration rates of membrane distillation and permeation distillation both depend on the pressure difference of water vapor maintained on both sides of the membrane. The difference is that the pressure difference of water vapor in membrane distillation is caused by the temperature difference on both sides of the membrane, while permeation distillation depends on the apparent osmotic pressure difference on both sides of the membrane. Compared with evaporation concentration and reverse osmosis, membrane distillation and permeation distillation do not require pressure and operate at low temperature and pressure. Especially, permeation distillation can also be carried out at room temperature, which avoids the influence of high temperature or high pressure on the concentrated liquid, better maintains the original color, aroma, and taste, and reduces the degree of membrane fouling. Especially during high concentration, the permeability rate of membrane distillation is significantly higher than that of reverse osmosis. The biggest limitation of membrane concentration is the low concentration factor, and high concentration factor is not economical. This technology is more economical and reasonable when used in conjunction with evaporation and concentration equipment.