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New technology of extraction and separation of natural products
New technology of extraction and separation of natural products

■ Normal temperature ultra-high pressure technology

High-pressure biochemical research shows that when the pressure reaches a certain value, organic macromolecules such as protein and polysaccharides (starch and cellulose) will be denatured, but small molecules such as alkaloids, oligosaccharides, steroids, terpenoids, glycosides, volatile oils and vitamins will not change.

In the research of high-pressure biochemistry, it is also proved that the mechanism of high-pressure sterilization is that pressure acts on microorganisms, which causes cell walls to denature and rupture, and cell contents to leak out, thus causing microorganisms to die. This cell change has also been confirmed in the high-pressure processing of meat, fish, fruits and vegetables.

Ultra-high pressure extraction is the use of ultra-high pressure on biological materials to extract effective components. There are many micropores in the plant cell wall, so we can regard the plant cell wall as a thin film composed of many micropores. When a plant cell is in a solvent, the solvent will enter the cell through these micropores.

1. When boosting:

Through osmosis, the solvent enters the cell; Because the pressure and flux we apply are very large, the cells will be filled with solvent in a short time.

After the cell is filled with solvent, the pressure on both sides of the cell wall is balanced.

2. When maintaining the pressure:

The contents of cells are contacted with solvents that enter cells, and after a period of time, the effective components are dissolved in these solvents.

3. When releasing the pressure:

The pressure outside the cell is reduced to zero, and the pressure inside the cell is still balanced. At this time, the pressure difference is opposite to that when pressure is applied. Because we are applying ultra-high pressure, the pressure difference in the opposite direction is still very large.

4. The cell wall is deformed under the action of reverse pressure; If the deformation exceeds its reverse deformation limit, the cell wall is destroyed; As a result, the solvent in which the active ingredient is dissolved leaks out and fuses with other solvents.

5. If the deformation of the cell wall does not exceed its reverse deformation limit under the reverse pressure, the solvent in which the effective components have been dissolved in the cell will be discharged through osmosis and merged with other solvents. Because of the great pressure difference in the opposite direction, the solvent in which the effective components are dissolved will leak out quickly and completely.

Normal temperature and ultra-high pressure extraction technology can use a variety of solvents, including organic solvents such as water and alcohols with different concentrations, and can extract effective components with different properties (such as alkaloids, flavonoids, saponins, polysaccharides, volatile oils, etc.) from different natural products.

■ Ultrasonic extraction technology

Ultrasonic wave is a kind of high-frequency mechanical wave. The ultrasonic field mainly provides energy to the system through ultrasonic cavitation. Ultrasonic waves with a frequency range of 15-60kHz are usually used to strengthen the process and initiate chemical reactions. Ultrasonic wave has played a certain role in the extraction of effective components from natural products. Its principle is to destroy the cell membrane by ultrasonic cavitation, which is helpful for the dissolution and release of effective components. Ultrasonic waves make the extract constantly oscillate, which is helpful for solute diffusion. At the same time, the thermal effect of ultrasonic makes the water temperature basically at 57℃, which has a water bath effect on raw materials. Compared with traditional reflux extraction and Soxhlet extraction, ultrasonic extraction has the advantages of fast extraction speed, short time, high yield and no need of heating. It has been selected as a means of sample treatment by many natural product analysis processes.

■ Microwave-assisted extraction technology

Microwave is a kind of non-ionizing electromagnetic radiation. Microwave-assisted extraction is a new technology to improve the extraction rate by using microwave energy. The extracted polar molecules quickly turn to directional arrangement in the microwave electromagnetic field, which causes tearing and mutual friction to generate heat, which can ensure the rapid transfer and full utilization of energy and is easy to dissolve and release. The study of microwave-assisted extraction (hereinafter referred to as microwave extraction) shows that microwave radiation-induced extraction technology has the characteristics of high selectivity, short operation time, low solvent consumption and high yield of effective components, and has been successfully applied to the extraction of medicinal materials and the extraction of effective components of traditional Chinese medicine. Its principle is that the molecules in medicinal materials collide and squeeze with each other by using the rapid vibration of 2.45 billion times per second generated by magnetron, which is beneficial to the leaching of effective components. In the extraction process, the medicinal materials are not caked and gelatinized, which overcomes the shortcomings of easy caking and gelatinization in hot water extraction.

Microwave extraction technology has some limitations and is only suitable for products that are stable to heat.

■ Enzymatic extraction technology

The cell wall of natural plants is composed of cellulose, and the effective components are often wrapped in the cell wall. Enzymatic method is a method using cellulase, pectinase, protease, etc. (mainly cellulase) destroys plant cell wall, which is beneficial to the maximum dissolution of effective components. Enzymatic reaction can gently decompose plant tissues, thus greatly improving the extraction efficiency.

■ Molecular distillation technology

Molecular distillation technology appeared in 1930s and has been widely used in many countries. China's molecular distillation technology has been successfully applied in medicine, fine chemicals, oil chemicals, food additives and other industries, and gradually gained attention in the Chinese medicine industry.

Under high vacuum, liquid molecules can overcome the internal attraction of liquid with little energy and leave the liquid surface to evaporate. Molecular distillation is the rapid separation of liquid at a temperature far below its boiling point, which depends on the difference of the average free path of molecular movement of the mixture under extremely high vacuum.

The free path of molecular motion refers to the path that a molecule travels between two adjacent collisions with other molecules. The average free path in a certain time interval is called the average free path of molecular motion. Under the condition of constant pressure and temperature, different kinds of molecules have different average free paths because of their different effective diameters. From a statistical point of view, after different kinds of molecules escape from the liquid surface, the flight distance is different without colliding with other molecules. The average free path of light molecules is large, and that of heavy molecules is large. If the distance between the condensation surface and the evaporation surface is less than the average free path of light molecules, but greater than the average free path of heavy molecules, light molecules can reach the condensation surface to be cooled and collected, while heavy molecules can't reach the condensation surface and return to the liquid surface to collide with each other, thus realizing the separation of mixed materials. Volatile oil plays an important role in natural products, and many volatile oils have strong physiological activities, but the extraction, purification and preparation of volatile oil have always been the difficulty in the research and development of natural products. Molecular distillation technology has great advantages and potential in separating and purifying volatile oil from natural products. Combined with supercritical fluid extraction, it not only exerts the characteristics of high extraction rate of supercritical oil and fully retains the effective components of volatile oil, but also achieves the effect of effective purification and separation of supercritical extract by molecular distillation.

■ Supercritical fluid extraction technology

Supercritical fluid extraction (SFE) is a new separation technology that rose in 1960s. Since the mid-1980s, SFE technology has been gradually applied to the extraction and separation of effective components from natural products due to its advantages of good selective separation effect, high extraction rate, no residual organic solvent in the products, and being beneficial to the extraction of heat-sensitive substances and oxidizing substances, and has been combined with GC, IR, GC-MS and HPLC to form an effective separation technology.

Supercritical fluid (SF) refers to the substance that exists in the form of fluid above the critical temperature (Tc) and critical pressure (Pc). At present, the most studied and commonly used supercritical fluid is carbon dioxide. SF is in contact with the substance to be separated in supercritical state, so that some components can be selectively dissolved. In a closed system, the density and dielectric constant of SF increase with the increase of pressure, so it can be made different by program boosting.

Gradually extract polar components. Then, the supercritical fluid is changed into ordinary gas by decompression, heating or adsorption, and the extract is separated and precipitated to achieve the purpose of separation and purification. This is the basic principle of supercritical fluid extraction.

At present, supercritical extraction technology is mainly used to extract the active components of natural products such as volatile oil, alkaloids, coumarin and lignans, flavonoids, terpenoids, glycosides and quinones.

■ Macroporous resin adsorption

Macroporous adsorption resin is a new polymer separation material developed in 1960s, and it is a kind of polymer adsorbent. According to its pore size, specific surface area and composition type, it can be divided into many types. At the end of 1970s, some Chinese scholars began to study the separation and purification of effective components from natural products.

The application principle of macroporous adsorption resin separation technology is mainly based on the principle of combining macroporous adsorption resin with molecular sieve, a special adsorbent, to selectively adsorb effective components from the extract of natural products and remove impurities. Especially nonpolar adsorption resin, when adsorbing the effective components in the extract, it is mainly physical structure (such as specific surface area, pore size, etc.). ) plays an adsorption role.

The basic procedures of separation and purification of macroporous adsorption resin are mostly: natural product extract is eluted step by step with macroporous resin, the effective component ethanol solution is adsorbed, and the solvent is recovered to obtain dried semi-finished extract. Macroporous adsorption resin technology can effectively enrich effective components such as flavonoids, alkaloids and glycosides in natural products.

■ Membrane separation technology

Membrane separation technology is a new and efficient separation technology, which is internationally recognized as the most promising major high-tech production technology from the end of the 20th century to the middle of the 20th century. It is a technology that uses natural or synthetic membranes with selective permeability to separate, classify, purify or enrich binary or multicomponent systems driven by external energy or chemical potential difference. Membrane separation technology (hereinafter referred to as membrane technology) includes ultrafiltration, microfiltration, nanofiltration and reverse osmosis.

At present, this technology is also widely used in the production of traditional Chinese medicine preparations, especially ultrafiltration technology, which has been more and more used in traditional Chinese medicine preparations since the 1990 s because of its high efficiency, energy saving and green characteristics.

The application principle of membrane separation technology is similar to that of mechanical sieve, and the separation of solute and solvent is realized by pressure drive. Small molecular weight solutes such as solvent (water) pass through the filter membrane with asymmetric microporous structure, while large molecular weight solutes.

And particles (such as protein, virus, bacteria, colloid, etc. ) is intercepted by the filter membrane, so as to achieve the purpose of separation, purification and concentration of products. Normal temperature operation, no phase change and low energy consumption.

Ultrafiltration technology can be used to filter out impurities (ineffective components) with relative molecular weight greater than tens of thousands in natural product water extract, such as cellulose, mucus, gum, pectin, starch, tannin, protein (except a few medicinal materials), resin and other components.

Ultrafiltration concentration is also extremely effective for active ingredients with relative molecular weight above several thousand. When some protein, peptides and polysaccharides are effective components of natural products, impurities with large molecular weight and other precipitable components should be removed as far as possible. And then concentrated by ultrafiltration, so that water, ineffective components of small molecules, inorganic salts, monosaccharides and other components are filtered by a filter membrane, and the purity of the product is improved. Using ultrafiltration membrane separation technology to concentrate and filter out water and small molecular weight impurities in the extract can save energy consumption and improve drug purity.

■ Clarification technology

In recent years, some new materials and technologies have been applied to the clarification of natural product extracts. Not only can that cost be reduce, the production period is shortened, but also the stability of the preparation and the content of effective component can be ensured. For example, the application of 10 1 fruit juice clarifier, chitin, ZTC natural clarifier in the clarification of extractive solution has largely solved the hunger problem caused by the classical ethanol precipitation method. 10 1 fruit juice clarifier is a water-soluble colloidal substance, which is safe and nontoxic, does not introduce impurities, and can be removed together with insoluble substances after precipitation. Chitin (such as chitosan) is positively charged and can settle negatively charged suspended solids in the extract. ZTC natural clarifier can remove unstable components such as tannin, protein and colloid, but has little effect on effective components.

■ Molecular imprinting technique

Molecular imprinting technique is a highly selective separation technique that appeared at the end of the 20th century. This technology is to select functional monomers that can interact specifically with imprinted molecules and polymerize with cross-linking agents around imprinted molecules to form a three-position cross-linked polymer network. Then, the imprinted molecules are removed by a suitable solvent, and holes with complementary space and chemical functions are formed in the polymer network. The whole polymerization process can be divided into three steps: imprinting, polymerization and removal of imprinted molecules.

Xie Jianchun et al. prepared molecularly imprinted polymer (MIP) with acrylamide as functional monomer and quercetin as imprinted molecule in polar solvent by non-valence method. The experiment of liquid chromatography shows that. MIP has specific affinity for quercetin. Molecularly imprinted polymers were directly used to separate the hydrolysate of Ginkgo biloba extract, and two kinds of yellow pigments mainly containing quercetin and kaempferol, a compound with similar structure to quercetin, were obtained.

The composition of ketone. Some studies have confirmed the feasibility of MIT directly separating and extracting compounds with specific effects from Chinese herbal medicines.