Coenzyme Q10 production method

In the early 1980s, Japan realized the synthetic production of coenzyme Q10 from tobacco leaves by extracting lycopene alcohol as the raw material, and the cost of coenzyme Q10 has been greatly reduced, which has played an important role in promoting the application, popularization and promotion of coenzyme Q10. Semi-chemical synthesis method is technically more mature, has achieved industrialization, low cost and moderate price. However, although the products produced by semi-chemical synthesis method have an advantage in price, there is a big gap between the products produced by bio-extraction method and those produced by bio-extraction method. The reason is that the biological extraction method is a natural, organic products, easy to be absorbed by the body transformation, while the chemical synthesis method is an artificial chemical synthesis of organic products, biological activity is very poor, not easy to be absorbed by the body, it is difficult to give full play to the pharmacological effects of Coenzyme Q10. Coenzyme Q10 chemical synthesis method has been a hot spot of research at home and abroad, in the past half a century, after the developed countries realized the microbial fermentation method of coenzyme Q10 production in 1977, the microbial fermentation and extraction method has been greatly developed in recent years, this new bioengineering method, not only synthesizes the advantages of the biological extraction process and the chemical synthesis process of the two methods, but also overcomes the shortcomings of the two methods, and is the most promising way to achieve the goal of coenzyme Q10 production, which is the most promising way to achieve the goal of coenzyme Q10 production. This new bioengineering method combines the advantages of both biological extraction and chemical synthesis processes, and overcomes their shortcomings, so it is the most impressive method with the hope of industrialization.

There are two main requirements for the industrialization of microbial fermentation and extraction:

(1) a stable and large-scale production of high-quality coenzyme Q10 transgenic strains;

(2) high-precision separation instrument technology. Japan is the earliest and the most dominant producer of coenzyme Q10 in the world. According to statistics, 90% of global coenzyme Q10 comes from Japan. The two Japanese companies with the highest production of CoQ10 are "Nissin Powder" and "Kyowa Fermentation".

Numerous experts have researched and explored CoQ10 in two ways: one is the introduction of decaprenol into the parent compound, and the other is the introduction of a shorter side chain into the parent compound, followed by the introduction of the desired long chain.

The synthesis of coenzyme Q10 using the route shown in formula (1) was reported in 1959 by R. Ruegg et al. Although the product was obtained, the yield was only 20% and the application of this method was limited by the fact that the allylated reagent made from cannabinol was a mixture of cis- and trans-isomers, which needed to be separated.

In 1972, Sato K. et al. reported the synthesis of coenzyme Q10 using the route shown in Eq. where Ni was used as a catalyst in step 4 of the reaction and the two phenolic hydroxyl groups were protected, which increased the yield of the coupling to some extent (28%). The main problem with this route was the instability of the allylic portion under acidic conditions, which made it difficult to maintain the conformation of the double bond.In 1979, Naruta Y. et al. reported the reaction of isoprene portions with quinone by using the strong nucleophilicity of the stannane and a BF3OEt2 catalyst at low temperatures (-78 to -60 °C).The results were satisfactory for the geometrical conformation of coenzyme Q10, which was obtained by using Ni as a catalyst in step 4 and protecting the two phenolic hydroxyl groups. A product with a satisfactory geometrical configuration (E/Z=85/15) was obtained, but the yield was only 51% in terms of isopentadienylstannane, and the synthetic route is shown in Fig. 3. Subsequently, Naruta Y. extended his method to the syntheses of VK1 and VK2. As can be seen from the above synthetic routes, such methods use the reaction of the parent compound with a polyisoprene-based compound, a

critical step that is not very high in yield. Therefore, this synthesis strategy cannot be considered ideal. As early as 1978, Terao S. used coenzyme Q7 to synthesize coenzyme Q10, because the raw material coenzyme Q7 is very expensive, so the practical value of this route is not very large. 1979, the group used the formula shown in the route for the synthesis of very productive, the raw material used by the route of inexpensive and easy to obtain, the reaction conditions are milder, the side chain and the mother nucleus of the compound with a high yield of binding (90.9% of the disappearance of the. In rats, the drug concentration in tissues such as lung, heart, liver and kidney increased at 4 hrs after dosing, and in adrenal, liver and gastric tissues at 10 hrs, 7 days after administration of the drug), only the chain synthesis with numerous steps resulted in a decrease in the total yield.In 1982, Sato K et al. improved the above mentioned route as well as the reagents used in varying degrees as shown in the formula (5), wherein the last step yielded up to 83% and the geometrical configuration of the double bond was satisfactory (E/Z=100/0).

China began to conduct technical research on coenzyme Q10 from the 1970s, and soon constructed several production lines for the bioextraction method, which was mainly extracted from porcine myocardium, and the main domestic units using the bioextraction process for the production of coenzyme Q10 were Beijing Pharmaceutical Factory, Taizhou Biochemical Pharmaceutical Factory, Qingdao Biochemical Pharmaceutical Factory, Hangzhou Pharmaceutical Factory, Changsha Biochemical Pharmaceutical Factory, Zhejiang Tiantai County Pharmaceutical Factory, Guiyang Biochemical Pharmaceutical Factory, Wuju Biochemical Pharmaceutical Factory, Taiyuan Biochemical Pharmaceutical Factory, Datong Biochemical Pharmaceutical Factory and so on a dozen enterprises. The total production capacity is around 600kg.

China is the world's major tobacco producer, China has a large number of can not be used for cigarettes, the waste of secondary tobacco, unutilized, resulting in environmental pollution and waste of resources. As early as in the late 1970s, China began to carry out research and development work on the extraction of cannabinol from waste tobacco leaves.

In the early 1990s, China invested a lot of energy in the research of the new process of Coenzyme Q10, and achieved promising results. Henan University Tobacco Chemistry Science and Technology Development Institute and Shangqiu Tobacco Fine Chemical Factory cooperation **** with the research and development of the use of tobacco extracted from the potaniol, based on years of research, in January 1996 to formally realize the industrialization of the annual output of 100 tons of crude potaniol content of ≥ 15% and 20 tons of content of ≥ 75% of the potaniol boutique products for the industrialization of China's production of coenzyme Q10 laid a good foundation. The foundation is laid for the industrialized production of Coenzyme Q10 in China. Coenzyme Q10 has two main roles in the body, one is to play an important role in the conversion of nutrients into energy in the mitochondria, and the other is to have obvious anti-lipid peroxidation effect. It is an energy converter in the cell mitochondria, which participates in the "tricarboxylic acid cycle" by transferring and transmitting electrons to produce ATP (adenosine triphosphate), an energy factor for cellular metabolism. In humans, the ability to synthesize Coenzyme Q10 on its own peaks at the age of 20 and is maintained until about 50 years of age. After that, the capacity to synthesize coenzyme Q10 on its own decreases every year, because the mitochondrial DNA material of the cells hosting coenzyme Q10 is damaged by oxygen radicals, leading to a decrease in the autonomous synthesis of coenzyme Q10. As a result, the metabolic function of human cells, especially heart cells, decreases, and "old age" becomes apparent.

Experiments have shown that in vivo coenzyme Q10 becomes alcoholic and reacts directly with peroxide radicals and can regenerate vE, which alone and in concert with vE plays the role of an antioxidant. In vitro experiments also found that the antioxidant coenzyme Q10 can protect mammalian cells from apoptosis triggered by mitochondrial oxidative stress, while the tumor necrosis factor - (TNF- ) or oncogene inhibitors do not have such a role, clinical studies have shown that oral coenzyme Q10 for the treatment of Parkinson's syndrome, Huntington's chorea and Alzheimer's disease and other neurodegenerative diseases associated with mitochondrial dysfunction and aging has a significant efficacy.

Experiments on the relationship between aging and mitochondrial coenzyme Q10 concentration have shown that a decrease in mitochondrial coenzyme Q10 concentration is an important aspect of skeletal muscle aging. An experimental study of aging in rats showed that mitochondrial coenzyme Q10 levels were reduced in the heart of aging rats, and even lower in the liver and skeletal muscle. The decline in immune function with age is a result of free radicals and free radical reactions. Coenzyme Q10 is a potent antioxidant and free radical scavenger, which is embedded in mitochondrial inner membrane lipid bilayers as part of the mitochondrial respiratory chain, and turns into an alcoholic form after accepting two electrons from either mitochondrial complex I or complex II, and then transfers the electrons to complex III. In vivo, CoQ10 is consumed in large quantities to turn into an alcoholic form, which is a potent antioxidant as well as an electron carrier for movement. , which transfers hydrogen atoms from its hydroxyl group to lipid peroxidation radicals, thus reducing the lipid peroxidation reaction in the inner mitochondrial membrane. In this process, the free radical ubiquinone, which is disproportionate to coenzyme Q10 and the alcohol form of coenzyme Q10, is generated, or it reacts with oxygen to form superoxide, and the free radical ubiquinone transports the free radicals to achieve detoxification under the action of superoxide dismutase and catalase, and the respiratory chain of the cycle will continually re-generate the alcohol form of coenzyme Q10, which restores its antioxidant active role.

Decline in immune function with age is the result of free radicals and free radical reactions. Coenzyme Q10 as a strong antioxidant used alone or in combination with vitamin B6 (pyridoxine) can inhibit free radicals from modifying microtubular systems associated with cell differentiation and activity on receptors on immune cells, enhance the immune system, and slow down the aging process.

The increase of wrinkles and the aging of the skin are related to the content of Q10, the lower the content, the easier the skin aging, and the more wrinkles on the face. Q10 can be ingested through oral intake, and when the cells contain enough Q10, that is, the energy metabolism will be enhanced, to remove free radicals, and to alleviate the aggravation of wrinkles.

In addition, you can also rub skin care products containing coenzyme Q10, improve the external application can also increase the cellular absorption of coenzyme Q10, thereby reducing the formation of wrinkles. In the mid-1970s, Mitchell's theory of the chemical osmosis hypothesis revealed the conversion of energy in living organisms and the important role of coenzyme Q10 in the mitochondrial energy conversion system.

Coenzyme Q10 is a coenzyme for at least three mitochondrial enzymes (multi-enzyme complexes I, II, and III), and it has the chemical structure of a 2,3-dimethoxy-5-methyl 1,4-benzoquinone derivative with a ten-unit isoprene side chain attached to the 6-position carbon.

The quinone ring plays a role in transferring electrons and protons in the oxidative respiratory chain, a role that is not only essential for all forms of life, but also key to the formation of ATP. ATP is the main form of energy storage in the organism, and it is also the important basis for all cellular functions to play normally. The biological activity of Coenzyme Q102.2 Detection wavelength: 275nm mainly comes from the redox properties of its quinone ring and the physicochemical properties of its side chain. It is a natural antioxidant and cell metabolism initiator produced by the cells themselves, with the protection and restoration of the integrity of the biological membrane structure, stabilize the membrane potential, is the body's non-specific immune enhancer, so it shows excellent anti-fatigue effect, Coenzyme Q10 makes the cells maintain a good and healthy state, and thus the body is full of vitality, energetic, and full of brain power. Chronic fatigue syndrome (CFS) etiology and pathology is still unclear, research shows that oxidative stress is a cause of the disease, experiments have found that patients with CFS are varying degrees of oxidative stress, although the oxidative damage is the cause or the result of the disease needs to be further observation, but the antioxidant coenzyme Q10 has been successfully used in the prevention and treatment of chronic fatigue syndrome.

In addition, the antioxidant properties of coenzyme Q10 give it an inhibitory role in the formation and development of atherosclerosis. Moreover, its antioxidant properties make good effects such as membrane stabilization, metabolic cardioversion and reversal of left ventricular hypertrophy, which are increasingly used in cardiovascular diseases. Local experiments show that with the increase of age the ability of skin collagen to resist damage by oxidative stimuli such as ultraviolet light decreases, and the long-term use of coenzyme Q10 can effectively prevent skin photo-aging and reduce wrinkles around the eyes, because coenzyme Q10 penetrates into the growth layer of the skin can attenuate the oxidative reaction of photons, and with the assistance of tocopherol, it can activate the specific phosphorylation of tyrosine kinases to prevent DNA oxidative damage, inhibit the expression of collagenase in human skin fibroblasts under UV light exposure, and protect the skin from damage. Extensive research has concluded that Coenzyme Q10 inhibits lipid peroxidation, reduces the generation of free radicals, protects the SOD activity center and its structure from oxidative damage caused by free radicals, improves the activity of SOD and other enzymes in the body, inhibits oxidative stress-induced apoptosis, and has a significant antioxidant and ageing-prolonging effect.

It is able to penetrate deep into the cells, strengthen the cell metabolism function, activate the intercellular tightness bonding ability, on the other hand, in the epidermal layer of the shape of the gel elastic mesh structure, really repair the wrinkles due to the loss of water caused by the wrinkles, and then to achieve the real moisturizing effect.

Features: It can repair the skin with unsound keratin, such as thin skin or the problem of keratin atrophy caused by overdose of medicated cosmetics, which can be improved by using it for 3-6 months.

Used for importing can increase the absorption of effective ingredients, and increase the resistance of cells, the effect is the most perfect, improve the skin dehydration problem more thoroughly. Coenzyme Q10 antioxidant, can destroy free radicals, maintain the integrity and stability of cell membranes. Coenzyme Q10 is used as an adjuvant treatment for the following diseases

1, cardiovascular diseases, such as: toxic myocarditis, chronic cardiac insufficiency.

2, hepatitis, such as: viral hepatitis, subacute hepatic necrosis, chronic active hepatitis.

3, comprehensive treatment of cancer: can reduce some of the adverse reactions caused by radiotherapy, chemotherapy and so on.