Main Applications of Methionine Hydroxy Analogs_Kain Industrial Additives

Background and overview^[1]

MethionineHydroxyAnalogue (MHA) is a highly acidic liquid organic acid with a water content of 12wt% and 88wt% of active methionine hydroxyl analogues (including 2-hydroxy-4 with a content of at least 65wt% – Methylthiobutyric acid monomer, and 2-hydroxy-4-methylthiobutyric acid dimers and polymers in an amount not exceeding 23% by weight). In poultry feeding, methionine hydroxy analogues show properties similar to amino acids known to have a growth-stimulating effect and are therefore important additives to animal feeds. One of the synthesis methods of methionine hydroxyl analogues is the cyanohydrin hydrolysis method, which is to react methylthiopropionaldehyde with hydrocyanic acid to obtain 2-hydroxy-4-methylthiobutyronitrile, which is hydrated under the action of sulfuric acid to form 2- Hydroxy-4-methylthiobutanamide is further hydrolyzed under the action of sulfuric acid to obtain a hydrolyzate containing a methionine hydroxyl analogue, ammonium sulfate and ammonium bisulfate. There have been many reports on methods for separating and purifying methionine hydroxyl analogues from 2-hydroxy-4-methylthiobutyronitrile hydrolyzate. For example: one method is to add 2-hydroxy-4-methylthiobutyronitrile hydrolyzate to water-immiscible organic solvents such as ketones, ethers, etc. for extraction, extract the methionine hydroxyl analogue into the organic solvent, and then evaporate After removing the organic solvent, a methionine hydroxyl analogue is obtained, and the aqueous phase containing ammonium sulfate is concentrated under reduced pressure and crystallized by cooling to obtain ammonium sulfate.

The problem with this method is that the use of organic solvent extraction not only results in the loss of organic solvent and increases the production cost of methionine hydroxyl analogues, but also the organic solvent and methionine hydroxyl analogues will remain in the aqueous phase, resulting in COD of external drainage. On the high side, it is difficult to process biochemically; the obtained methionine hydroxyl analogue will also contain organic solvents, which must be distilled under high vacuum or steam should be introduced into them to reduce the content of organic solvents. These all lead to the cost and cost of this method. The energy consumption is high; in addition, because the solubility of methionine hydroxyl analogues in water is relatively large, the use of organic solvents for extraction cannot completely extract the methionine hydroxyl analogues from the water phase. Therefore, a certain amount must remain in the water phase. The methionine hydroxyl analogues cause the by-product ammonium sulfate to contain a small amount of methionine hydroxyl analogues, which has a certain odor and affects the sales of ammonium sulfate.

Apply^[2]

1. Nutritional effects

It has been proven that methionine hydroxyl analogues are natural precursors of methionine. Although they do not contain amino groups, they can be converted into the unique carbon framework of methionine under the action of enzymes in animals, and can be converted into methionine, so they have the characteristics of methionine. biological activity. When methionine is synthesized into body proteins in animals, it can be converted into cystine, which plays a role in liver protection and detoxification. It is the most important methyl donor in the animal body. It provides active methyl groups to the body and participates in the transfer of methyl groups and the secretion of adrenaline and bile. The synthesis of alkali, keratin and nucleic acids is metabolized in the body to generate polyamines. Polyamines play a very important role in promoting animal cell proliferation and are also involved in the synthesis of spermine, semispermine and other compounds related to cell division.

2. Improve growth performance

Methionine hydroxyl analogues can effectively act as acidifiers in the diet, buffering the neutralization of gastric acid by highly alkaline ingredients in the diet, enhancing the acidic environment of the gastrointestinal tract, and increasing the activities of pepsin and duodenal trypsin. This promotes the digestion and absorption of nutrients, especially protein, and promotes growth. This is consistent with reports that acidifiers can promote gastric acid and pepsin secretion, increase duodenal digestive enzyme activity, and promote piglet growth. Li Junyou et al. confirmed that the absorption of nutrients depends on the integrity of the intestinal absorptive cell membrane. Damage to the intestinal mucosa results in the destruction of a large number of absorptive cells, seriously affecting the absorption function of the small intestine. It can reduce intestinal mucosal damage, maintain the absorption function of the small intestine, and promote growth. In addition, the cost is low, and during the feed processing process, it can improve the mixing uniformity and reduce classification, reduce dust, increase the output of pellets, reduce energy consumption per ton of pellets, and bring considerable economic benefits.

3. Reduce heat stress response

Under climate conditions of high temperature and high humidity, since methionine hydroxyl analogues do not contain amino groups, the waste heat generated during the conversion into uric acid is reduced, thus slowing down the heat stress response of chickens. In vitro experiments show that when chickens are under heat stress, the transport of methionine in the small intestine is weakened, while the transport of methionine hydroxyl analogs is enhanced, and the utilization rate of methionine under heat stress conditions is also smaller than that of methionine hydroxyl analogs. Heat stress can induce the occurrence of oxidative stress. Research by Fu Yuqiang and others found that as the temperature increases during heat stress, the activity and activity of liver mitochondrial respiratory chain complex enzymes decrease, resulting in mitochondrial respiratory chain electron transfer disorders. The activity of purine oxidase is enhanced, more free radicals are produced, and the degree of oxidative stress is enhanced. Studies have shown that oxidative stress induced by heat stress is closely related to the body’s antioxidant system. Heat stress mainly affects the redox balance in the animal body, putting oxidants in the body in a dominant position, thus damaging tissues and cells. Therefore, it is speculated that it may reduce the degree of oxidative stress in the body by slowing down heat stress, thereby playing an antioxidant role.

4. Immunity

Methionine hydroxyl analogs have the effect of improving the body’s immunity, but its mechanism is not yet clear. Most of the current research levels remain on the measurement of apparent immune indicators. Study the effects of different additive dosages on broiler performance and…The results showed that adding methionine hydroxyl analogues to the diet can improve the feed utilization, humoral immunity and non-specific immune activity of broilers. This is mainly due to the fact that during the metabolism of methionine hydroxyl analogues, they prefer the transsulfurization pathway, transferring sulfur-containing methyl groups to cysteine, glutamine, and taurine. These molecules play an important role in immune regulation. Other studies have found that high-fat meals can induce chronic oxidative stress, inhibit gut-associated lymphocyte signaling, and lead to mucosal immunosuppression, and the antioxidant lipoic acid can improve oxidative stress and immunosuppression caused by high fat, so it is speculated that It can improve the body’s immunity, possibly by increasing the body’s antioxidant capacity, and has similar functions to the antioxidant lipoic acid.

5. Antibacterial effect and reduce diarrhea rate

Methionine hydroxyl analogue is a highly acidic organic acid that affects the neutral to alkaline environment in which pathogenic bacteria survive. It can directly diffuse into pathogenic bacteria cells, reduce the intracellular content, inhibit the synthesis of DNA and RNA, and destroy pathogenic bacteria. The integrity of the cell membrane achieves bacteriostatic and bactericidal effects.

Preparation^[1]

A clean and environmentally friendly production method for methionine hydroxyl analogues:

1) Pass 327.50kg (2000 moles) of 2-hydroxy-4-methylthiobutyronitrile aqueous solution with a mass content of 80wt% and 150.00kg (1500 moles) of sulfuric acid with a mass content of 98wt% through the flow rate At the same time, the material is added to the static mixer to mix thoroughly. At this time, the temperature rises rapidly to 45°C, and then enters the tubular reactor. The inlet temperature of the material in the tubular reactor is 48°C, and the outlet temperature is 55°C. The material is in the tube. The residence time in the reactor is 40 minutes. The material flow in the tubular reactor is added to the enamel reactor with stirring, and water is added at the same time. The amount of water added is 280.00kg. After the addition, the temperature is immediately raised to 100°C for hydrolysis, and the mixture is stirred and kept warm for 3 hours to obtain yellow. The mixed liquid is brown and uniform. When cooled to 60°C, the mixed liquid does not appear turbid or solid. The mass percentage content of the methionine hydroxyl analogue was analyzed to be 39.60wt%.

2) The hydrolyzate obtained above is subjected to continuous chromatographic separation. During chromatographic separation: the feed flow rate is 12 to 18 liters/minute, the eluent flow rate is 20 to 30 liters/minute, and the discharge flow rate is 14 to 20 liters/minute. minutes, and the eluent outflow flow rate is 18 to 28 liters/minute. The temperature in the continuous chromatography column is maintained at 60°C to 70°C, and the temperature of the eluent is 65°C. 1500.00kg of methionine hydroxyl analog aqueous solution and 840.56kg of ammonium sulfate aqueous solution with a mass percentage content of 20.00wt% were obtained respectively. The mass percentage content of the methionine hydroxyl analogue in the ammonium sulfate aqueous solution was 0.12wt%, which were stored in the ammonium sulfate aqueous solution storage. In the tank, the temperature is 62°C, and the mass percentage of ammonium ions in the methionine hydroxyl analogue is 0.015wt%. It is stored in a storage tank of the methionine hydroxyl analogue aqueous solution, and the temperature is 65°C.

3) Concentrate the solution in the above methionine hydroxyl analog aqueous solution storage tank with the MVR evaporator until the mass percentage of the methionine hydroxyl analogue is 59wt%, then transfer it to a wiped film evaporator for concentration, and wiped film evaporation The temperature of the reactor is 110°C, and it is concentrated to a mass percentage of 88wt%. 339.98kg of methionine hydroxyl analogue is obtained. The appearance color is a yellow-brown oily liquid. The mass percentage of the monomer is analyzed to be 78wt%. The mass percentage of polymers and multimers is 10wt%, the moisture content is 12wt%, the mass percentage of ammonium ions is 0.066wt%, and the yield of methionine hydroxyl analogues is 99.73%. The condensed water recovered by evaporation is recycled to hydrolysis water and chromatography elution water.

4) Add the above-mentioned ammonium sulfate aqueous solution storage tank into the reaction kettle with neutralization, then introduce ammonia gas for neutralization, control the pH value during neutralization to 5-6 as the neutralization end point, and obtain sulfuric acid Ammonium aqueous solution, the ammonium sulfate aqueous solution is concentrated by MVR evaporation device, crystallized and centrifuged under high temperature conditions to obtain ammonium sulfate wet product. After drying, the by-product ammonium sulfate is obtained. The mass percentage of ammonium sulfate is 99wt%. Ammonium sulfate The recovery rate is greater than 99%, the appearance is white, and there is almost no smell. The condensed water recovered by evaporation is recycled to hydrolysis water and chromatography elution water.

Main reference materials

[1] CN201811329839.4 A clean and environmentally friendly production method for methionine hydroxyl analogs

[2] Antioxidant effect of methionine hydroxyl analogues and its effect on mouse growth