Dihydropyridines, whose chemical name is 2, 6-dimethyl-3, 5-bis (alkoxycarbonyl)-1, 4-Dihydropyridines, is a new multi-functional feed additive having wide bio-functions. It is used as health-caring medicine for curing cardiovascular diseases in medicine having the effects on curing liver steatosis, toxic liver hepatitis, cognition in aging, and sexual precocity.

The bio-functions of Dihydropyridines
1：Anti-oxidant
Dihydropyridines has anti-oxidization effect. It can inhibit the oxidization of bio-membranes in body, improve the activity of 6-glucan phosphorylase in the bio-membrane, make the cells in the tissues stable, and has some functions of the natural anti-oxidant—Vitamin E. Dihydropyridines can form a complex combined with terminal oxidase cytochrome P450 and significantly inhibit the activity of NADPH-Cytochrome C reductase, and continual intake of Dihydropyridines has not other influences on microsomal enzyme. The anti-oxidization of Dihydropyridines in animal’ bodies may be that it inhibits the over-oxidization of fatty compounds through blocking the activity of microsomal electron transferring NADPH enzyme and cleaning the formed free radicals. Dihydropyridines can significantly improve the activity of superoxide dismutase (SOD) in blood serum, and SOD is the main cleaning agent of superoxide free radicals in body, which can inhibit over-oxidization of fatty compounds. Dihydropyridines can reduce the oxidization lost of some nutrients in feed such as VA and carotenoid and improve their utilization rate, it can also prevent fats and oils from oxidization and prolong their storing term.

2：Endocrine regulation of animals and poultries
Dihydropyridines can significantly improve the thyroid-stimulating hormone (TSH) content in serum, which plays an important role in normal growth and development of the body as well as normal reproduction. TSH can promote the differentiation of organs and tissues, and has an “allowance effect” on growth hormone. Dihydropyridines can also significantly improve the contents of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the serum, promote the growth and development of follicle indirectly. Additionally, Dihydropyridines can improve cAMP content in hypothalamus and adenohypophysis, promote the synthesis of many proteins, thus it can promote the growth and development of animals and poultries.

3：Improvement of the immunity of animals and poultries
Dihydropyridines can perfect the immune function of the body and improve its immunity. Dihydropyridines can improve 25.62% (P<0.05) degree of serum Newcastle disease antibody of the treatment group to that of the control group, and improve 25.12 percentage of ANAE lymphocytosis cells to that of the control group. Addition of Dihydropyridines in chicken dietary feed can improve the number of T- and B-type lymphocytosis cells in the serum of chickens and increase the weights of their thymus glands and cloacal bursa.

4：Promotion of minerals digestion and adsorption
Addtion of Dihydropyridines combined with ferrous- and Zinc-agents in the dietary feed of egg-laying hens can improve feed utilization rate and promote the adsorption and utilization of minerals.

Application of Dihydropyridines in Animal & Poultry Feeding Industry
Dihydropyridines has broad application scope and different reports of its effects in China and foreign countries. In summary, all the reports showed that it had positive effect and its negative effect have not been reported to date. Dihydropyridines feeding tests conducted by relative national and international scholars with cows, breeding bulls, hens, ducks, pigs, and minks as the subjects showed that Dihydropyridines had significant effectiveness, which are summarized as the following aspects:

1：Improvement of daily gain and feed utilization rate of animals and poultries and the perfecting of products’ quality
Addition of Dihydropyridines (20-50mg/kg) in the dietary feed of broiler chickens could improve their daily gains and feed utilization rate. Dihydropyridines has fairly well effects on the promotion of pig growth and the reduction of feed consumption. Research showed that when added Dihydropyridines to the dietary feed of growing & fattening pigs, the mean daily gain and feed/meat ratio of the treatment group improved 5.2% and reduced 3.4% to that of the control group, respectively. Addition of 0.01% Dihydropyridines in the dietary feed of sheep could improve the daily gains as much as 19.07%, 13.44%, and 18.25% of females, males, and youths, respectively. Some reported that addition of Dihydropyridines could improve the daily gain of minks. Addition of 100-150mg/kg Dihydropyridines in the dietary feed of the broilers could significantly improve the daily gains and flavoring substances content in the muscle; Addition of 50mg/kg Dihydropyridines in the feed of growing & fattening pigs with 60-100 kg body weight could significantly promote their growth and development, improve their slaughter rate and carcass lean ratio, significantly improve inosinc acid content, and perfect meat quality.

2：Improvement of the reproduction performance of animals and poultries
Dihydropyridines can improve 16.6% sperm motility, 18.7% intact rate of actosome, 12.9% semination volume, and reduce 37.2% sperm aberration rate. Addition of 0.025% Dihydropyridines in hare granular feed can significantly improve sperm quality of the males and the fertility rate of the females. Addition of 0.01% Dihydropyridines in the dietary feed of sheep improved 6.11% fertility rate of the females, 13.75% semen volume of the males, 8.53% sperm density, and 39.6% total sperm quantity. Addition of 200mg/kg and 250mg/kg Dihydropyridines in the dietary feed of domestic hares, the male sperm quantity of the treatment group improved 28.3% and 45.28% to that of the control group; the sperm mortality of the treatment group improved 53.13% and 78.13% to that of the control group with significant difference; and the female fertility rate of the treatment group improved 10.02% and 100.03% to that of the control group. According to relative report, Dihydropyridines can improve 30% pregnancy rate of cows. From 15-20 d before pregnancy to suckling pigs being 20 d old, addition of 0.01% Dihydropyridines in the dietary feed of pregnant pigs could improve 6.06% body weight of the larva pigs. The results mentioned above show that Dihydropyridines has good effect on the reproduction performance of animals and poultries.

3: Improvement of milk yield of domestic animals
In 1970s, Valdman et al. found that addition of Dihydropyridines in cow feed improved 33.9 % of the mean milk yield and 4.2% of the milk/fat rate after three months. Xiaoting Zheng et al. reported that addition of Dihydropyridines in cow dietary feed improved milk yield significantly (P<0.05). Wuhan Cows Company added 0.01% Dihydropyridines in cow dietary feed improving 13.1% of the total milk yield and 7.13% milk yield per cow, respectively. Dihydropyridines can not only improve cow feed intakes but also promote milk generation significantly, and it remains non-residue in the milk. Additionally, feeding test with nursing pigs showed that the total weight of the larva pigs per livestock of the treatment group was higher than that of the control group, this shows that addition of Dihydropyridines has benefit on improvement of milk yield of the nursing pigs.

Improvement of egg-laying of domestic poultries
Jufang Chen et al. added 0.015% Dihydropyridines in the feed of laying hens, which improved later egg-laying rate, thus prolonged egg-laying term and reduced feed index, the egg-laying rate of hens improved 11.61 %-17.17 %, and saved 13.48 % cost. Addition of 0.015% Dihydropyridines in the dietary feed of breeding ducks improved 6.4% egg-laying rate and 4.8% feed conversion ratio. Xiaoting Zhou reported that addition of 150mg/kg Dihydropyridines in the egg-laying hens’ feed obtained the best effect, the egg-laying rate of the treatment group improved 11.08 % to that of the control group, and the feed/egg ratio reduced 10.36%, additionally, the compound had the effects of improving the yolk index and the thickness of egg crust. Xianjun Wu et al. reported that addition of 150mg/kg ester-soluble Dihydropyridines in the dietary feed of egg-laying hens could significantly improve the egg-laying rate.

Safety and dosage of Dihydropyridines
Safety of Dihydropyridines
Odydants et al. studied the systematic pharmacological and toxicological effects of Dihydropyridines. Dihydropyridines has ever used in the experiments of internal distribution, discharging, blood serum, and embryos in the subjects of big white mice and domestic hares, the results showed that the intake Dihydropyridines was absorbed by stomach and intestine and was discharged along with urine, and the labeled metabolites in urine & faece excreta account for 97%-99% of that of the total intaking food. It seldom residues in other organs and tissues, thus it does not generate mutation and embryo-toxication in the bodies of animals. Toxic test of Dihydropyridines oral inoculation using male small white mice showed that its LD50 value was more than 10000mg/kg, belonging to non-toxic substance; it showed negative in small mice backbone micronucleus test and Salmonella mutation test. All of these tests show that Dihydropyridines is non-toxic and safety for feeding.
Dosage of Dihydropyridines
Dihydropyridines is available for various animals and poultries such as pigs, hens（cocks, chickens）, ducks, cows (battle, ox, bull)，goats (sheep), hares, silkworms, and minks.
Adding dosage in feeds:
Hens and ducks: 0.015%
Cattles (ox): 0.01-0.015% or 4-6mg/kg body weight
Goats (sheep): 0.01%
Pigs: 0.02%
Korean hares: 0.025%
Minks: 0.1%
Silkworms: 0.05% solution.
Addition method: blend Dihydropyridines with a little fine feed evenly, and then gradually blend it with all the feeds. It can be processed in dust or granular, but the feed should be fed immediately after preparation or blending to obtain perfect effect.
Prospect

As a green feed additive, Dihydropyridines is widely used in production in foreign countries, but it’s still at testing stage in China yet, most of the researches are conducted on feeding effects, many problems should be further discussed, for example, metabolism of Dihydropyridines in body; the mutual relations among Dihydropyridines, other anti-oxidants, Vitamin A, and Vitamin E; the stability of Dihydropyridines; mechanism of various generated functions of Dihydropyridines; moderate adding stages and dosages of Dihydropyridines in the growth and development of different animals and poultries, etc. Many testing results showed that Dihydropyridines had strong stabling effect on Vitamin A, Vitamin E, and carotenoids, it also can improve the impregnate (fertilization) rate, hatching rate, egg laying rate, semen quality, milk yield, daily gain, and feed conversion ratio, as well as reduce the feeding cost. It is a multi-functional feed additive using trace dosage to produce high efficiency, thus it has broad applied prospect.

In summary, Dihydropyridines is a new multi-functional green feed additive. It can significantly promote the growth of domestic animals, domestic fowls, fish, shrimps, and silkworms, perfect the reproduction performance, the body immunity, the slaughter rate, the meat quality and flavors. Additionally, it has also part functions of Vitamin E with feeding safety without any toxic or secondary effects. It is a perfect feed additive recommended by many experts and a growth promoter firstly approved by the Agriculture Ministry to use in China.