Application of melatonin or melatonin salt in improving weaning body condition of newborn intrauterine delayed-development baby

Abstract

The invention belongs to the field of animal husbandry, and particularly relates to application of melatonin or melatonin salt to improvement of weaning body conditions of newborn intrauterine delayed-development piglets. The invention accidentally finds that the concentration of the melatonin in the peripheral blood, colostrum and normal milk of the female livestock can be improved by treating the female livestock with the melatonin or the salt thereof in the period from delivery to lactation, so that the weaning body condition of the newborn IUGR baby lactated by the female livestock can be improved at the same time, and the melatonin or the salt thereof has important significance on improving the weaning body condition of the newborn IUGR baby. The method is simple in implementation step, good in effect and high in generalizability.

Description

Technical Field

[0001] The present invention belongs to the field of animal husbandry, and particularly relates to the application of melatonin or its salt in improving the weaning condition of neonates with intrauterine growth retardation. Background Art

[0002] In recent years, with the improvement of breeding techniques, although the litter size of pigs has increased significantly, it has brought problems such as reduced birth weight and low survival rate of piglets. Intrauterine growth retardation (IUGR) refers to the fact that the fetus / placenta of mammals is affected by various negative effects during pregnancy, resulting in growth retardation in the uterus. Eventually, it is manifested as imperfect morphological and functional development of the placenta and other organs, and the weight is significantly lower than that of fetuses of the corresponding physiological age, which will seriously affect the health and subsequent development of piglets. In China, the proportion of IUGR fetal pigs can be as high as 15 - 25%. IUGR piglets have the defect of high morbidity and mortality before weaning (up to 40%), resulting in about 22 pigs weaned per sow per year (PSY), which is lower than that in developed pig industry countries (25 - 27 pigs). At the same time, the weaned surviving piglets generally have defects such as slow growth, low feed utilization rate, high prevalence rate and poor meat quality, which seriously affect the economic benefits of the pig industry in China. Therefore, improving the weaning weight and condition of neonatal IUGR piglets is crucial for the development of the pig industry.

[0003] Currently, in the pig industry, in order to improve the condition of neonatal piglets, farmers increase the feed nutrition of lactating sows. In addition, reasonable supplementary feeding measures are taken for weaned piglets. However, in actual production, the above treatment schemes have high requirements (such as large-scale breeding, farmers having relevant breeding techniques, etc.), and the implementation work is cumbersome, making it not easy to be specifically implemented and widely promoted.

[0004] Melatonin (MT) is a hormone secreted by the pineal gland. Currently, studies have shown that melatonin is involved in regulating various biological processes such as biological rhythms, sleep and immune cells. There is no report on improving the weaning condition of neonates with intrauterine growth retardation by melatonin.

[0005] Therefore, in view of the problems existing in the prior art, it is necessary to seek a simple and effective method to improve the weaning condition of neonatal IUGR piglets, which is crucial for the development of the pig industry. Summary of the Invention

[0006] The purpose of the first aspect of the present invention is to provide the application of melatonin or its salt in improving the weaning condition of neonates with intrauterine growth retardation or in preparing a product for improving the weaning condition of neonates with intrauterine growth retardation.

[0007] The object of the second aspect of the present invention is to provide a method for improving the weaning condition of neonates with intrauterine growth retardation.

[0008] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0009] The first aspect of the present invention provides the use of melatonin or a salt thereof in any one of a1)-a2);

[0010] a1) improving the weaning condition of neonates with intrauterine growth retardation;

[0011] a2) preparing a product for improving the weaning condition of neonates with intrauterine growth retardation.

[0012] In some embodiments, the improvement of the weaning condition of neonates with intrauterine growth retardation in a1)-a2) includes any one of b1)-b4):

[0013] b1) increasing the weaning weight of neonates with intrauterine growth retardation;

[0014] b2) increasing the weaning body length of neonates with intrauterine growth retardation;

[0015] b3) increasing the weaning heart weight of neonates with intrauterine growth retardation;

[0016] b4) increasing the weaning spleen weight of neonates with intrauterine growth retardation.

[0017] In some embodiments, the product in a2) further includes an instruction manual, which describes a method for improving the weaning condition of neonates with intrauterine growth retardation.

[0018] In some embodiments, in a1), or in the instruction manual of the product in a2), the method for improving the weaning condition of neonates with intrauterine growth retardation is as follows: administering melatonin or a salt thereof to a female livestock that nurses the neonates with intrauterine growth retardation.

[0019] In some embodiments, in a1), or in the instruction manual of the product in a2), the method for improving the weaning condition of neonates with intrauterine growth retardation is as follows: administering melatonin or a salt thereof to the female livestock from before parturition to during lactation of the female livestock that nurses the neonates with intrauterine growth retardation.

[0020] In some embodiments, the neonates with intrauterine growth retardation may be the biological offspring of the female livestock or may not be the biological offspring of the female livestock.

[0021] In some embodiments, the administration method of the melatonin or a salt thereof includes oral administration, nasal administration, inhalation, parenteral administration, intravenous administration, intraperitoneal administration, subcutaneous administration, intramuscular administration, intradermal administration, topical administration or rectal administration; further preferably oral administration.

[0022] In some embodiments, the dosage of melatonin or its salt is 1.5 - 2.5 mg / kg livestock per day. For example, it can be 1.5 mg / kg livestock per day, 1.6 mg / kg livestock per day, 1.7 mg / kg livestock per day, 1.8 mg / kg livestock per day, 1.9 mg / kg livestock per day, 2.0 mg / kg livestock per day, 2.1 mg / kg livestock per day, 2.2 mg / kg livestock per day, 2.3 mg / kg livestock per day, 2.4 mg / kg livestock per day, 2.5 mg / kg livestock per day, or any value therebetween; further preferably 1.8 - 2.2 mg / kg livestock per day; more preferably 1.9 - 2.1 mg / kg livestock per day; even more preferably 2 mg / kg livestock per day. Calculated based on the weight of a livestock such as a sow being 200 kg, the amount of melatonin fed to each sow per day is 0.4 g.

[0023] In some embodiments, the number of times of administration of melatonin or its salt is 1 - 3 times per day; further preferably 1 time per day.

[0024] In some embodiments, the time of administration of melatonin or its salt is every morning (preferably from 7 to 8 o'clock every morning).

[0025] The level of melatonin in the body is relatively low during the day. Using the method of single administration in the morning can effectively increase the melatonin level during the day, which helps the utilization of melatonin.

[0026] In some embodiments, melatonin or its salt is added to the feed for administration to female livestock.

[0027] In some embodiments, the period before parturition is 1 - 10 days before the expected date of delivery. For example, it can be 10 days, 9 days, 8 days, 7 days, 6 days, 5 days, 4 days, 3 days, 2 days, 1 day before the expected date of delivery, or any value therebetween.

[0028] In some embodiments, the period before parturition is 5 - 7 days before the expected date of delivery.

[0029] In some embodiments, the period before parturition is 5 days before the expected date of delivery.

[0030] In some embodiments, the number of days of administration of melatonin or its salt is 33 ± 5 days. For example, it can be 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, or any value therebetween.

[0031] In some embodiments, the number of days of administration of melatonin or its salt is 33 ± 2 days.

[0032] In some embodiments, the number of days of administration of melatonin or its salt is 33 days.

[0033] In some embodiments, the livestock are selected from: pigs, cows, horses, sheep, rabbits, dogs, and cats; further preferably pigs.

[0034] In some embodiments, the young animals in a1) and a2) are selected from: piglets, calves, foals, lambs, rabbit kits, puppies, and kittens; further preferably piglets.

[0035] In the present invention, the newborn intrauterine growth retardation young animals are newly born intrauterine growth retardation young animals.

[0036] In some embodiments, the application in a1) does not involve the diagnosis and / or treatment of diseases.

[0037] In some embodiments, the salt comprises at least one of metal salts, ammonium salts, salts formed with organic bases, salts formed with inorganic acids, salts formed with organic acids, salts formed with basic amino acids, and salts formed with acidic amino acids.

[0038] In some embodiments, the metal salt comprises at least one of alkali metal salts (e.g., sodium salt, potassium salt, etc.), alkaline earth metal salts (e.g., calcium salt, magnesium salt, barium salt, etc.), and aluminum salts.

[0039] In some embodiments, the salt formed with an organic base comprises a salt formed with one or more of the following organic bases: trimethylamine, triethylamine, pyridine, methylpyridine, 2,6-dimethylpyridine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N,N'-dibenzylethylenediamine.

[0040] In some embodiments, the salt formed with an inorganic acid comprises a salt formed with one or more of the following inorganic acids: hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid.

[0041] In some embodiments, the salt formed with an organic acid comprises a salt formed with one or more of the following organic acids: formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid.

[0042] In some embodiments, the salt formed with a basic amino acid comprises a salt formed with one or more of the following basic amino acids: arginine, lysine, ornithine.

[0043] In some embodiments, the salt formed with an acidic amino acid comprises a salt formed with one or more of the following acidic amino acids: aspartic acid, glutamic acid.

[0044] In some embodiments, the product is a feed additive or feed.

[0045] The second aspect of the present invention provides a method for improving the weaning body condition of neonates with intrauterine growth retardation, comprising administering melatonin or a salt thereof to female livestock breastfeeding the neonates with intrauterine growth retardation.

[0046] In some embodiments, the method for improving the weaning condition of neonates with intrauterine growth retardation comprises any one of b1) to b4):

[0047] b1) Increase the weaning weight of newborn pups with intrauterine growth retardation;

[0048] b2) Increase the weaning length of newborns with intrauterine growth retardation;

[0049] b3) Increase the heart weight of newborn pups with intrauterine growth retardation at weaning;

[0050] b4) Increase the spleen weight at weaning in neonatal IUGR pups.

[0051] In some embodiments, the method comprises the step of administering melatonin or a salt thereof to the female livestock breastfeeding the intrauterine growth retardation neonate before delivery to during the lactation period.

[0052] In some embodiments, the intrauterine growth retardation neonate may be the biological child of the female livestock or may not be the biological child of the female livestock.

[0053] In some embodiments, the administration of melatonin or its salt comprises oral, nasal, inhalation, parenteral, intravenous, intraperitoneal, subcutaneous, intramuscular, intradermal, topical or rectal administration; further oral.

[0054] In some embodiments, the dosage of melatonin or its salt is 1.5-2.5 mg / kg livestock.day, for example, 1.5 mg / kg livestock.day, 1.6 mg / kg livestock.day, 1.7 mg / kg livestock.day, 1.8 mg / kg livestock.day, 1.9 mg / kg livestock.day, 2.0 mg / kg livestock.day, 2.1 mg / kg livestock.day, 2.2 mg / kg livestock.day, 2.3 mg / kg livestock.day, 2.4 mg / kg livestock.day, 2.5 mg / kg livestock.day, or any value therebetween; further 1.8-2.2 mg / kg livestock.day; further 1.9-2.1 mg / kg livestock.day; further 2 mg / kg livestock.day. Calculated based on the weight of livestock, such as sows, at 200 kg, the amount of melatonin fed to each sow per day is 0.4 g.

[0055] In some embodiments, the melatonin or a salt thereof is administered 1-3 times / day; further once / day.

[0056] In some embodiments, the melatonin or its salt is administered in the morning every day (preferably from 7 to 8 o'clock in the morning every day).

[0057] The level of melatonin in the body is relatively low during the day. The method of administering a single dose in the morning can effectively increase the melatonin level during the day, which helps the utilization of melatonin.

[0058] In some embodiments, the melatonin or its salt is added to the feed and administered to female livestock.

[0059] In some embodiments, the period before parturition is 1 - 10 days before the expected date of delivery. For example, it can be 10 days, 9 days, 8 days, 7 days, 6 days, 5 days, 4 days, 3 days, 2 days, 1 day before the expected date of delivery, or any value therebetween.

[0060] In some embodiments, the period before parturition is 5 - 7 days before the expected date of delivery.

[0061] In some embodiments, the period before parturition is 5 days before the expected date of delivery.

[0062] In some embodiments, the number of days of administration of the melatonin or its salt is 33 ± 5 days. For example, it can be 28 days, 29 days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37 days, 38 days, or any value therebetween.

[0063] In some embodiments, the number of days of administration of the melatonin or its salt is 33 ± 2 days.

[0064] In some embodiments, the number of days of administration of the melatonin or its salt is 33 days.

[0065] In some embodiments, the livestock are selected from: pigs, cows, horses, sheep, rabbits, dogs, and cats; further preferably pigs.

[0066] In some embodiments, the young animals are selected from: piglets, calves, foals, lambs, rabbit cubs, puppies, and kittens; further preferably piglets.

[0067] In the present invention, the newborn intrauterine growth retardation cubs are newly born intrauterine growth retardation cubs.

[0068] In some embodiments, the method does not involve the diagnosis and / or treatment of diseases.

[0069] In some embodiments, the salt comprises at least one of metal salts, ammonium salts, salts formed with organic bases, salts formed with inorganic acids, salts formed with organic acids, salts formed with basic amino acids, and salts formed with acidic amino acids.

[0070] In some embodiments, the metal salt comprises at least one of an alkali metal salt (e.g., sodium salt, potassium salt, etc.), an alkaline earth metal salt (e.g., calcium salt, magnesium salt, barium salt, etc.), and an aluminum salt.

[0071] In some embodiments, the salt formed with an organic base comprises a salt formed with one or more of the following organic bases: trimethylamine, triethylamine, pyridine, methylpyridine, 2,6-dimethylpyridine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N,N'-dibenzylethylenediamine.

[0072] In some embodiments, the salt formed with an inorganic acid comprises a salt formed with one or more of the following inorganic acids: hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid.

[0073] In some embodiments, the salt formed with an organic acid comprises a salt formed with one or more of the following organic acids: formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid.

[0074] In some embodiments, the salt formed with a basic amino acid comprises a salt formed with one or more of the following basic amino acids: arginine, lysine, ornithine.

[0075] In some embodiments, the salt formed with an acidic amino acid comprises a salt formed with one or more of the following acidic amino acids: aspartic acid, glutamic acid.

[0076] The beneficial effects of the present invention are:

[0077] The present invention unexpectedly discovers that treating with melatonin or its salt from before parturition to during lactation of female livestock can increase the melatonin concentration in the peripheral blood, colostrum, and normal milk of female livestock. Based on this, it can simultaneously improve the weaning body condition of the neonatal IUGR offspring nursed by the female livestock, which is of great significance for improving the weaning body condition of neonatal IUGR offspring. The method of the present invention has simple implementation steps and good effects, and at the same time has strong popularization potential.

[0078] Furthermore, by adding melatonin or its salt to the feed for administration to livestock, the method of the present invention is simple and easy to operate, does not cause stress reactions in livestock, and has strong feasibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0079] Figure 1The melatonin levels in the peripheral blood, colostrum, and normal milk of sows in the melatonin group and the control group are shown: Among them, A shows the comparison of MT concentrations in the peripheral blood of sows in the melatonin group and the control group; B shows the comparison of MT concentrations in the colostrum of sows in the melatonin group and the control group; C shows the comparison of MT concentrations in the normal milk of sows in the melatonin group and the control group.

[0080] Figure 2 The weaning body conditions of neonatal IUGR piglets in the melatonin group and the control group are shown: Among them, A shows the comparison of weaning weights of neonatal IUGR piglets in the melatonin group and the control group; B shows the comparison of weaning body lengths of neonatal IUGR piglets in the melatonin group and the control group; C shows the comparison of weaning heart weights of neonatal IUGR piglets in the melatonin group and the control group; D shows the comparison of weaning spleen weights of neonatal IUGR piglets in the melatonin group and the control group. Detailed implementation manners

[0081] Definition

[0082] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly used in the field to which the present invention belongs. For the purpose of explaining this specification, the following definitions will be applied, and where appropriate, terms used in the singular form will also include the plural form, and vice versa.

[0083] The term "about" as used herein means a range of ±20% of the value following it. In some embodiments, the term "about" means a range of ±10% of the value following it. In some embodiments, the term "about" means a range of ±5% of the value following it.

[0084] The content of the present invention is further described in detail below through specific examples.

[0085] It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention.

[0086] The experimental methods in the following examples that do not specify specific conditions are generally carried out under conventional conditions or according to the conditions recommended by the manufacturer. The materials, reagents, etc. used in this example, unless otherwise specified, are reagents and materials obtained from commercial sources. For reagents indicating the manufacturer, similar products from other manufacturers are substitutable.

[0087] Experimental methods

[0088] 1. Melatonin treatment protocol

[0089] In the following examples, the starting time point of melatonin treatment was 5 days before the expected delivery date of pregnant sows, and the ending time point was when the piglets were weaned. The total melatonin feeding time was 28 + 5 days, that is, 33 days. The feeding dose for each pig was 2 mg / kg (the weight of the sow was calculated as 200 kg, and the daily feeding amount for each pig was 0.4 g). The melatonin feeding time point every day was from 7:00 to 8:00 in the morning, and the feeding method was feed addition.

[0090] 2. Collection of blood, colostrum, and normal milk samples

[0091] The blood collection time point for lactating sows was two days before the piglets were weaned. The blood collection method was anterior vena cava blood collection in the neck for analyzing melatonin changes. The colostrum collection time point was when the sow gave birth. The normal milk collection time point was two days before the piglets were weaned.

[0092] 3. Determination of melatonin content

[0093] In the following examples, the melatonin concentration was determined by LC-MS / MS detection. (For the specific detection method, see the reference: Wang X, Liu T, Lv X, Sun N, Li F, Luo L, Zhuge X, Huang J, Wang L. A Potential Nontraditional Approach To Combat tmexCD1-toprJ1-Mediated Tigecycline Resistance: Melatonin as a Synergistic Adjuvant of Tigecycline. Antimicrob Agents Chemother. 2023 Jul 18;67(7):e0004723.doi:10.1128 / aac.00047-23.Epub 2023 Jun 8.PMID:37289048;PMCID:PMC10353380.).

[0094] 4. Determination of weaning weight, body length, heart, and spleen of weaned piglets

[0095] On the day of weaning, the weaning weight, body length, heart weight, and spleen weight of the piglets were measured.

[0096] Example 1

[0097] 1. Variation law of melatonin in peripheral blood and colostrum after feeding melatonin

[0098] Select 10 healthy sows 5 days before the expected due date (i.e., 5 days away from the expected due date), and randomly divide them into a melatonin group (MT, 5 sows) and a control group (5 sows). The control group was fed normally. The melatonin group was treated with melatonin starting from 5 days before the expected due date until the piglets were weaned. Colostrum of sows was collected at parturition, and blood and normal milk of sows were collected two days before the piglets were weaned. The concentration of melatonin in peripheral blood, colostrum and normal milk was detected by LC-MS / MS method, and the measurement results are shown in Figure 1 .

[0099] Figure 1 In Figure 1 , A is the change in MT concentration in peripheral blood, specifically as follows: (0.8742 ± 0.3718 VS 18.59 ± 7.258, mg / mL) n = 5 (unit: head); B is the change in MT concentration in colostrum, specifically as follows: (8.727 ± 4.532 VS 72.18 ± 23.74, mg / mL) n = 5 (unit: head); C is the change in MT concentration in normal milk, specifically as follows: (11.44 ± 3.093 VS 115.1 ± 37.22, mg / mL) n = 5 (unit: head). The above data are expressed as: control group VS melatonin group, and all data are expressed as mean ± standard error. Different letters indicate significant differences within the group (p < 0.05), and the same letter indicates no significant difference within the group (p > 0.05).

[0100] By Figure 1 It can be seen that from 5 days before sow parturition to piglet weaning, treating sows with 2 mg / kg of melatonin can significantly increase the melatonin concentration in the peripheral blood of sows (0.8742 ± 0.3718 VS 18.59 ± 7.258, mg / mL) (p < 0.05); detecting the melatonin concentration in colostrum, it was found that the melatonin concentration in the colostrum of sows in the melatonin-fed group (MT) was significantly higher than that in the control group (8.727 ± 4.532 VS 72.18 ± 23.74, mg / mL) (p < 0.05); detecting the melatonin concentration in normal milk, it was found that the melatonin concentration in the normal milk of sows in the melatonin-fed group (MT) was significantly higher than that in the control group (11.44 ± 3.093 VS 115.1 ± 37.22, mg / mL) (p < 0.05).

[0101] 2. Changes in the relevant physical conditions of weaned piglets after feeding melatonin

[0102] Select 10 healthy sows 5 days before the expected due date and randomly divide them into a melatonin group (MT, 5 sows) and a control group (5 sows). The control group was fed normally. Two female IUGR piglets, two male IUGR piglets, two female normal piglets, and two male normal piglets were randomly assigned to each sow (i.e., based on "1. Changes in melatonin in peripheral blood and colostrum after melatonin feeding". After the piglets were born, they were assigned within the group according to their body weight. That is, the IUGR piglets and normal piglets born to the sows in the melatonin group were assigned to the sows in the melatonin group for feeding according to their body weight (the piglets fed by the sows are not necessarily their own offspring), and the IUGR piglets and normal piglets born to the sows in the control group were assigned to the sows in the control group for feeding according to their body weight (the piglets fed by the sows are not necessarily their own offspring)). The melatonin group was treated with melatonin starting 5 days before the expected due date until the piglets were weaned. On the day of weaning, the weaning weight (i.e., the body weight of the piglets at weaning), weaning body length (i.e., the body length of the piglets at weaning), weaning heart weight (i.e., the heart weight of the piglets at weaning), and weaning spleen weight (i.e., the spleen weight of the piglets at weaning) were measured. The measurement results are shown in Figure 2 .

[0103] Figure 2 In Figure 2 , A shows the change in weaning weight of IUGR piglets at weaning, specifically as follows: (5.900 ± 0.2543 VS 6.833 ± 0.2486, kg) n = 4 (unit: head); B shows the change in body length of IUGR piglets at weaning, specifically as follows: (45.42 ± 1.228 VS 49.00 ± 0.4472, cm) n = 4 (unit: head); C shows the change in heart weight of IUGR piglets at weaning, specifically as follows: (37.54 ± 2.916 VS 48.80 ± 3.702, g) n = 4 (unit: head); D shows the change in spleen weight of IUGR piglets at weaning, specifically as follows: (14.86 ± 1.064 VS 19.83 ± 1.881, g) n = 4 (unit: head). The above data are expressed as: control group VS melatonin group. All data are expressed as mean ± standard error. Different letters indicate significant differences within the group (p < 0.05), and the same letters indicate non-significant differences within the group (p > 0.05).

[0104] Through Figure 2It is known that from 5 days before farrowing to weaning of piglets, sows were treated with 2 mg / kg melatonin, and the weaning weight, body length, heart weight and spleen weight were measured. It was found that melatonin treatment could significantly increase the weaning weight (5.900 ± 0.2543 VS 6.833 ± 0.2486, kg), body length (45.42 ± 1.228 VS 49.00 ± 0.4472, cm), heart weight (37.54 ± 2.916 VS 48.80 ± 3.702, g) and spleen weight (14.86 ± 1.064 VS 19.83 ± 1.881, g) of IUGR piglets (p < 0.05).

[0105] The above results indicate that by adding melatonin to the feed and treating sows during the pre-farrowing and lactation periods with 2 mg / kg melatonin, the melatonin concentration in the peripheral blood, colostrum and normal milk of sows can be significantly increased; at the same time, melatonin treatment can significantly increase the weaning weight, body length, heart weight and spleen weight of IUGR piglets. Therefore, melatonin can improve the weaning condition of neonatal IUGR piglets.

[0106] The technical solution of the present invention is not limited to the limitations of the above specific embodiments. Any technical deformation made according to the technical solution of the present invention falls within the protection scope of the present invention.

Claims

1. Use of melatonin or a salt thereof in any one of items a1) to a2); a1) Improve the body condition of newborn pups with intrauterine growth retardation at weaning; a2) Preparation of products for improving the weaning body condition of neonates with intrauterine growth retardation.

2. The use according to claim 1, characterized in that: The improvement of the weaning body condition of neonatal intrauterine growth retardation pups mentioned in a1)-a2) comprises any one of b1)-b4): b1) Increase the weaning weight of newborn pups with intrauterine growth retardation; b2) Increase the weaning length of newborns with intrauterine growth retardation; b3) Increase the heart weight of newborn pups with intrauterine growth retardation at weaning; b4) Increase the spleen weight at weaning in neonatal IUGR pups.

3. The use according to any one of claims 1-2, characterized in that: The product described in a2) further comprises instructions, which record a method for improving the weaning body condition of newborn cubs with intrauterine growth retardation; Preferably, in the instructions of the product described in a1) or a2), the method for improving the weaning body condition of neonates with intrauterine growth retardation is as follows: administering melatonin or a salt thereof to female livestock breastfeeding the neonates with intrauterine growth retardation; Preferably, in the instructions of the product described in a1) or a2), the method for improving the weaning body condition of neonates with intrauterine growth retardation is as follows: administering melatonin or a salt thereof to the female livestock that is breastfeeding the neonates with intrauterine growth retardation before delivery and during the lactation period.

4. The use according to claim 3, characterized in that: The administration of melatonin or its salt comprises oral, nasal, inhalation, parenteral, intravenous, intraperitoneal, subcutaneous, intramuscular, intradermal, topical or rectal administration; further oral administration; Preferably, the melatonin or its salt is administered in an amount of 1.5-2.5 mg / kg livestock.day; Preferably, the administration amount of melatonin or its salt is 1.8-2.2 mg / kg livestock / day.

5. The use according to any one of claims 3 to 4, characterized in that: The melatonin or its salt is added into feed and administered to female livestock; Preferably, the period before delivery is 1-10 days before the expected date of delivery; Preferably, the period before delivery is 5-7 days before the expected date of delivery.

6. The use according to any one of claims 3 to 5, characterized in that: The melatonin or its salt is administered for 33±5 days; Preferably, the melatonin or its salt is administered for 33±2 days.

7. The use according to any one of claims 3 to 6, characterized in that: The livestock is selected from the group consisting of pigs, cattle, horses, sheep, rabbits, dogs and cats; further selected from the group consisting of pigs.

8. The use according to any one of claims 1 to 7, characterized in that: The offspring in a1) and a2) are selected from the group consisting of piglets, cattle, horses, sheep, rabbits, dogs and cats; furthermore, piglets; Preferably, the salt comprises at least one of a metal salt, an ammonium salt, a salt formed with an organic base, a salt formed with an inorganic acid, a salt formed with an organic acid, a salt formed with a basic amino acid, and a salt formed with an acidic amino acid; Preferably, the product is a feed additive or a feed.

9. A method for improving the weaning body condition of a neonate with intrauterine growth retardation, comprising administering melatonin or a salt thereof to a female livestock breastfeeding the neonate with intrauterine growth retardation.

10. The method according to claim 9, characterized in that The method for improving the weaning body condition of newborns with intrauterine growth retardation comprises any one of b1) to b4): b1) Increase the weaning weight of newborn pups with intrauterine growth retardation; b2) Increase the weaning length of newborns with intrauterine growth retardation; b3) Increase the heart weight of newborn pups with intrauterine growth retardation at weaning; b4) Increase the spleen weight of newborn pups with intrauterine growth retardation at weaning; Preferably, the method is the method for improving the weaning condition of newborns with intrauterine growth retardation as described in any one of claims 3 to 8; Preferably, the salt comprises at least one of a metal salt, an ammonium salt, a salt formed with an organic base, a salt formed with an inorganic acid, a salt formed with an organic acid, a salt formed with a basic amino acid, and a salt formed with an acidic amino acid.

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