阅读说明：本技术 用于改善哺乳动物健康和行为表现的饲料 (Feed for improving health and performance of mammals ) 是由 艾玛·沃尔 于 2019-03-11 设计创作，主要内容包括：本发明涉及含有高甜度甜味剂与辣椒油树脂组合的饲料添加剂。更确切地说,本发明涉及一种为了制备哺乳动物成品饲料而添加到饲料中的饲料添加剂,包括至少一种高甜度甜味剂与辣椒油树脂组合；其中所述高甜度甜味剂与所述辣椒油树脂的重量比小于或等于25:1。本发明还涉及一种包含上述饲料添加剂的成品饲料,以所述成品饲料的总重量计,上述饲料添加剂的含量大于零且小于或等于200ppm。此外,本发明涉及使用上述饲料添加剂或成品饲料改善哺乳动物(特别是兔子、猪和牛犊)在畜牧学方面的行为表现。(The present invention relates to a feed additive comprising a high intensity sweetener in combination with capsicum oleoresin. More specifically, the present invention relates to a feed additive for addition to feed for the preparation of a finished feed for mammals, comprising at least one high intensity sweetener in combination with capsicum oleoresin; wherein the weight ratio of the high intensity sweetener to the capsicum oleoresin is less than or equal to 25: 1. The invention also relates to a finished feed containing the feed additive, wherein the content of the feed additive is more than zero and less than or equal to 200ppm based on the total weight of the finished feed. Furthermore, the invention relates to the use of the above feed additive or finished feed for improving the performance of mammals, in particular rabbits, pigs and calves, in zootechnics.)

1. A feed additive for preparing a finished feed for mammals comprises

-at least one high intensity sweetener; and

-a capsicum oleoresin combination;

wherein the weight ratio of the high-sweetness sweetener to the capsicum oleoresin is less than or equal to 25: 1.

2. The feed additive of claim 1 wherein the high intensity sweetener is an artificial high intensity sweetener.

3. The feed additive of claim 2, wherein the artificial high intensity sweetener is selected from the group consisting of: saccharin and its salts, acesulfame potassium, cyclamate, aspartame, sucralose, neotame, edmuntame, and combinations thereof.

4. The feed additive of claim 1 wherein the high intensity sweetener is a natural high intensity sweetener.

5. The feed additive according to claim 4, wherein said natural high intensity sweetener is selected from the group consisting of: stevia leaves, stevia extracts, steviosides (including steviol glycosides, rebaudioside a, rebaudioside C, dulcoside a, rubusoside, steviolbioside, rebaudioside B), and combinations thereof.

6. The feed additive of claim 5 wherein the steviol glycosides comprise at least 25 wt.% rebaudioside A.

7. A feed additive according to claim 6 comprising 66 wt% stevia extract (including at least 75 wt% steviol glycosides, of which at least 25 wt% rebaudioside A) and up to 3 wt% capsicum oleoresin (containing at least 6 wt% capsaicin (capsaicin and dihydrocapsaicin)).

8. A feed additive according to any one of claims 1 to 7 further comprising a synergist.

9. The feed additive of claim 8 wherein the potentiator is selected from the group consisting of: glycyrrhizin, ammonium glycyrrhizinate, potassium glycyrrhizinate, sodium glycyrrhizinate, thaumatin, kokumi, NHDC, ribonucleotides, sodium glutamate, and combinations thereof.

10. A finished feed comprising the feed additive according to any one of claims 1 to 9 in an amount greater than zero and less than or equal to 200ppm, based on the total weight of the finished feed.

11. A finished feed as claimed in claim 10 wherein if the high intensity sweetener is an artificial high intensity sweetener, the level is less than or equal to 100 ppm.

12. The finished feed of claim 11, wherein the artificial high intensity sweetener is present in an amount of less than or equal to 50 ppm.

13. The finished feed of claim 10, wherein if said high intensity sweetener is a natural high intensity sweetener, the amount is less than or equal to 180 ppm.

14. Use of a feed additive according to any one of claims 1 to 9 to improve the performance of mammals in zootechnics.

15. Use according to claim 14, wherein the mammal is a rabbit, pig and/or calf.

16. The use of claim 15, wherein the mammal is a rabbit.

17. Use of a finished feed according to any of claims 10 to 13 for improving the performance of mammals in zootechnics.

18. Use according to claim 17, wherein the mammal is a rabbit, pig and/or calf.

19. The use of claim 18, wherein the mammal is a rabbit.

20. The use according to any one of claims 14 to 19, wherein the zootechnical performance is selected from the group consisting of: feed intake, average daily gain and feeding efficiency.

Technical Field

The present invention relates to feed and feed additives containing high intensity sweeteners and/or capsicum oleoresin, and to their use for improving the health and performance of mammals.

Background

Enteritis is an infection of the digestive tract and can be caused by a variety of different pathogens. In rabbits, enteritis is a devastating disease, causing most illness, death, and economic loss. Young rabbits and weaned rabbits are particularly susceptible, with diarrhea as a primary symptom, and are associated with a reduced growth and behavior profile.

Colibacillosis is an enteritis caused by the bacterial pathogen escherichia coli, which infects the small and caecum of rabbits. Colibacillosis is common in young rabbits, and the death rate may be high; the disease can be transmitted from female rabbits to young rabbits, and the whole litter of young rabbits is generally affected by the disease. Weaned rabbits are particularly susceptible and, even if they survive, continue to perform poorly after the disease subsides.

The main treatments for colibacillosis in rabbits are antibiotic treatment and culling of infected animals (both of which cause significant economic losses). Antibiotic treatment is expensive and can lead to drug resistant strains and/or problems with drug residues in the meat of the animal. Therefore, additives (without antibiotics) that can prevent disease or help animals fight disease have attracted significant attention.

Phytonutrients are bioactive chemical substances that occur naturally in plants. It has been shown that the addition of a plant nutrient named capsicum oleoresin to the feed enhances immunity in monogastric animals, thus relieving oxidative stress (Karadas et al, 2014.Br Poult Sci.55: 329) and preventing disease symptoms (Liu et al, 2012.J Anim Sci.90:2774-2783, Lee et al, 2013.Br J Nutr.110:840-847, Liu et al, 2013.J Anim Sci.91:5668-5679, Liu et al, 2013.J Anim Sci.91: 5294-5306). Pepper oleoresin has also been shown to improve gut health in both normal and diseased states (Liu et al, 2014.J Anim Sci.92: 3426-.

Another feed supplement that can improve gut health is high-sweetness artificial and natural sweeteners. These molecules activate the sweet taste receptor T1R2/3 in the intestine (as described in document WO 2014033218), stimulating the secretion of glucagon-like peptide (GLP) -2 by enteroendocrine cells of the intestine (Moran et al, 2010 Br J Nutr.104: 637-646). GLP-2 is a potent gastroprotective agent that increases blood flow, stimulates mucosal growth, and prevents cell death during infectious inflammation (Connor et al, 2016.Domest Anim Endocrinol.56Suppl: S56-65). The reaction of the intestinal tract to the high-sweetness artificial and natural sweeteners is characterized by the increased villus height,

Increased nutrient absorption and increased tight junction strength, which in turn, together promote improved health and performance. Furthermore, document WO2014033218 describes the use of high-sweetness artificial and natural sweeteners to modify the intestinal microbiota and intestinal glucose absorption of monogastric animals.

The effective dose for these two additives is different, but the dosage of phytonutrients is typically between 20 and 400ppm, while the dosage of high intensity artificial and natural sweeteners is typically greater than 200ppm (Moran et al, 2010 Br JNeutr.104: 637-646, Moran et al, 2014J Dairy Sci.97:4955-4972, Ponce et al, 2014J Anim Sci.92:1630-1638, Siurana et al, 2014 J.Dairy Sci.97(E-Suppl.1):811 (Abstract), Connor et al, 2017J Dairy Sci.100: 3004-3018). These molecules are generally used in even higher doses, particularly in plant nutrients which are often used for their antimicrobial properties. The dosage used depends on the species, molecule being tested and the objective of the study.

In rabbits, the addition of capsicum in the form of crushed capsicum at a dose of 1% (10000ppm) of the rabbit diet, a decrease in body weight was observed (Yu et al, 2012, Mol Biol Rep.39: 7583-7589). In another study, various doses (0.5% to 2%; 5000 to 20000ppm) of powder containing capsicum frutescens were shown to lower blood glucose, but had no effect on rabbit performance (Dougnon and Gbasessor, 2016.Vet world.9: 281-. After approximately 1000ppm stevia extract was supplemented to hyperglycemic rabbits, blood glucose levels were reduced and liver glycogen levels were restored, indicating that high-sweetness natural sweeteners affect glucose metabolism (Aghajanyan et al, 2017.Biomed Res int.2017: 9251358). In both the hot pepper and high intensity sweetener studies on rabbits, the supplements were used in botanical form with no indication of component or active level. In addition, the dosages used are very high and have no effect on the health and performance of the animals.

Since most of the available literature on rabbits describes doses much higher than those beneficial for other species, and no study has been conducted in the context of intestinal disease, it is necessary to review published information on other species to gain insight. It was demonstrated that the addition of 10ppm capsicum oleoresin reduced the disease symptoms of piglets infected with E.coli (Liu et al, 2013.J Anim Sci.91: 5294-5306). In addition, the addition of 400ppm high intensity sweetener to breast-fed calves had a preventive effect on Cryptosporidium infection (Connor et al, 2017.J DairySci.100: 3004-one 3018).

The improvement of health and performance using plant extracts and/or high intensity artificial and natural sweeteners alone or in combination has not been explored. If these molecules could improve gut health in rabbits, it is possible to observe beneficial effects on animal performance, similar to those observed in other species.

Disclosure of Invention

The problem addressed by the present invention is to improve the health and performance of mammals, particularly rabbits, without the use of antibiotics. Based on the current state of knowledge, the inventors explored the use of high-intensity artificial and natural sweeteners or capsicum oleoresin for feeding alone and in combination. Surprisingly, it was previously established that doses beneficial to other species were actually very harmful to rabbits. Thus, the present invention describes a novel method of using additives to reduce the negative effects of enteritis on rabbits.

The use of the invention includes one or more of the following features:

supplementation of high-intensity sweeteners or capsicum oleoresin alone in very low doses improves the health (reduces mortality including diarrhea and bloating and morbidity) and performance (increases intake, daily gain and/or increases growth or feeding efficiency) of rabbits.

The use of these two additives in combination enhances the synergy of health (reduced mortality including diarrhea and bloating and morbidity) and performance (increased intake, daily gain and/or increased growth or feeding efficiency) in rabbits.

Use of high intensity sweeteners and capsicum oleoresin in various specific ratios to enhance the synergy of health (reduced mortality including diarrhea and bloating-and morbidity) and performance (increased intake, daily gain and/or increased growth or feeding efficiency) in rabbits.

Supplementation of the combination of high intensity sweetener and capsicum oleoresin at very low doses improves the performance of other mammals (including calves and piglets) in zootechnics.

Thus, according to a first aspect, the present invention relates to a feed comprising:

-at least one artificial high intensity sweetener in an amount greater than zero and less than or equal to 50 ppm; or

-at least one natural high intensity sweetener in an amount greater than zero and less than or equal to 180 ppm.

According to a second aspect, the invention relates to a feed wherein the capsicum oleoresin content is greater than zero and less than or equal to 2 ppm.

According to a third aspect, the invention relates to a feed additive comprising at least one high intensity artificial or natural sweetener and capsicum oleoresin, wherein the weight ratio of the high intensity sweetener to capsicum oleoresin is less than 100:1, preferably less than or equal to 25: 1.

Other features and advantages of the present invention will be described in detail in the following specification with reference to the accompanying drawings.

Drawings

Figure 1 shows that standard doses of artificial high intensity Sweetener (SW), natural high intensity Sweetener (SWN) or Capsicum Oleoresin (CO) increased mortality in e.coli inoculated rabbits (compared to control group ═ p)<0.01; compared with the control group, the compound of the formula,the values shown in the figure are the percent mortality relative to the control group.

Figure 2 shows that low doses of artificial high intensity Sweetener (SW), natural high intensity Sweetener (SWN) or Capsicum Oleoresin (CO) reduced mortality in e.coli inoculated rabbits (p <0.01 compared to control). The values shown in the figure are the percent mortality relative to the control group.

Figure 3 shows the synergistic effect of natural high intensity Sweetener (SWN) and Capsicum Oleoresin (CO) on reducing the incidence of e.coli vaccinated rabbits (P <0.01 compared to control; P <0.05 compared to control). The values shown in the figure are the number of onset relative to the control.

Fig. 4 shows that the number of attacks in E.coli inoculated rabbits decreased linearly, revealing the optimal weight ratio of natural high intensity Sweetener (SWN) to Capsicum Oleoresin (CO).

Figure 5 shows the synergistic effect of natural high intensity Sweetener (SWN) and Capsicum Oleoresin (CO) on increasing the growth efficiency of e.coli inoculated rabbits (P <0.10 compared to control). The figures show the ratio of body weight gain to feed consumption (relative to control).

Figure 6 shows that supplementation with various doses of natural high intensity Sweetener (SWN) and Capsicum Oleoresin (CO) (23SWN:2CO) at optimal weight ratios was effective in reducing the incidence of e.coli-inoculated rabbits (P <0.01 compared to the control). The values shown are the total number of episodes observed in each group over time.

Figure 7 shows that supplementation with 26ppm of natural high intensity Sweetener (SWN) and 2ppm of Capsicum Oleoresin (CO) was effective in reducing the number of veterinary treatments for calves.

Figure 8 shows that supplementation with 30ppm natural high intensity Sweetener (SWN) and 2ppm Capsicum Oleoresin (CO) was effective in increasing piglet weight.

Detailed Description

By "feed additive" is meant in the present invention an additive which is not intended to be used alone, but is used to be added to the usual ingredients of a conventional feed for mammals.

"finished feed" means in the present invention a feed which is ready for feeding to mammals and which is obtained after addition of the feed additive according to the invention.

The present invention proposes a novel method of improving the health (reducing mortality including diarrhea and bloating-and morbidity) and performance (increasing intake, daily gain and/or increasing growth or feeding efficiency) of mammals (including rabbits, pigs and calves) using low-dose high intensity sweeteners, capsicum oleoresin or a combination of both.

The invention may be used during normal feeding conditions or during periods when enteritis may occur.

The term "intestinal inflammation" as meant by the inventors refers to any inflammation of the gastrointestinal tract of a mammal, regardless of the cause (including, but not limited to: coccidiosis, enterotoxemia, colibacillosis, myxomatous enteritis, proliferative intestinal lesions, or tazetha).

The high intensity sweetener may be a high intensity artificial sweetener, a high intensity natural sweetener, or a combination of both.

High intensity artificial sweeteners useful in the present invention may include, without limitation: saccharin and its salts, acesulfame potassium, cyclamate, aspartame, sucralose, neotame, and edmuntin, alone or in combination. The high intensity artificial sweetener may also include a potentiator.

In the inventive process, the high intensity artificial sweetener comprises at least 96 wt% saccharin sodium and at least 0.2 wt% neohesperidin dihydrochalcone (NHDC).

In the course of the invention, it was found that very low doses of artificial high intensity sweeteners are beneficial for rabbit health (reducing mortality including diarrhea and bloating and morbidity) and performance (increasing intake, daily gain and/or increasing growth or feeding efficiency). The inventors first tested a reasonable dose based on the state of the art, since these doses (at a level of 150ppm in the feed) were previously determined to be beneficial to other small mammals. Surprisingly, the inventors found that this dose was very harmful to rabbits, as it greatly increased mortality during inflammatory bowel infection challenge. Next, the inventors tested the supplementation of rabbits with a new lower dose of 50ppm, followed by an enteritis infection challenge, and found that at this low dose, mortality was greatly reduced. The inventors have challenged colibacillosis infection after testing rabbits with a 50ppm dose, and have found that mortality is greatly reduced at this dose.

Therefore, the dose of the artificial high intensity sweetener for improving the health status (reducing mortality including diarrhea and bloating) and performance (increasing intake, daily gain and/or increasing growth or feeding efficiency) of rabbits in the present invention includes all doses of 50ppm or less in the finished feed.

High intensity natural sweeteners useful in the present invention may include, without limitation: stevia leaves, stevia extracts, steviosides (including steviol glycosides, rebaudioside a, rebaudioside C, dulcoside a, rubusoside, steviolbioside, rebaudioside B) or any other high intensity sweetener of natural origin are used alone or in combination. The high intensity sweetener of natural origin may also be derived from flowering plants and/or extracts thereof and/or active compounds: tunica (Pentadiplandra brazzeana) (pentadina and brazzein plant sweet proteins), Anisi Stellati (lllium verum), Piper nigrum (Pipermarginatum) or Jasminum sambac (Myrrhis odorata) (trans-anethole and estragole), Scorzonera arborescens (Osmorrhizial geneticatis) (anethole), grapefruit (Citrus paradis) (naringin), hydrangea (Hydranganarrophylla) (dihydrocoumarin). The high intensity natural sweetener may also include a potentiator.

In the inventive process of the present invention, the high intensity natural sweetener used comprises at least 75 wt% steviol glycosides of which at least 25 wt% is rebaudioside a and a potentiator: at least 0.3 wt% ammonium glycyrrhizinate.

The potentiator included in the high intensity artificial or natural sweetener may be selected from the list including, but not limited to: glycyrrhizin, ammonium glycyrrhizinate, potassium glycyrrhizinate, sodium glycyrrhizinate, thaumatin, kokumi, NHDC, ribonucleotide and sodium glutamate.

In the course of the invention, it was found that very low doses of high-intensity natural sweeteners are beneficial for rabbit health (reducing mortality including diarrhea and bloating and morbidity) and performance (increasing intake, daily gain and/or increasing growth or feeding efficiency). The inventors first tested a reasonable dose based on the state of the art, as this dose was previously determined to be beneficial to other small mammals (360 ppm in the feed). Surprisingly, the inventors found that this dose was very harmful to rabbits, as it greatly increased mortality during inflammatory bowel infection challenge. Next, the inventors tested supplementing rabbits with a new lower dose of 180ppm followed by an enteritis infection challenge and found that mortality was greatly reduced at this low dose.

Thus, the dosage of high-intensity natural sweetener for improving the health (reducing mortality including diarrhea and bloating and morbidity) and performance (increasing intake, daily gain and/or increasing growth or feeding efficiency) of rabbits in the present invention includes all dosages of 200ppm or less, preferably 180ppm or less in the finished feed.

Peppers useful in the present invention may include, but are not limited to: vegetable-derived (natural) capsicum oleoresin or any product containing at least 6 wt% capsaicin (capsaicin and dihydrocapsaicin). In the inventive process of the present invention, said capsicum oleoresin as a supplement is prepared by adding capsicum oleoresin (22 wt%) to 78 wt% rapeseed oil matrix (by spray cooling), which is described in document EP2088871 (US 20100055253; W02008062368). The final packaged product contained 20 wt% capsicum oleoresin.

In the course of the invention, it was found that very low doses of capsicum oleoresin are beneficial to the health (reduced mortality including diarrhoea and bloating-and morbidity) and performance (increased intake, daily gain and/or increased growth or feeding efficiency) of rabbits. The inventors first tested a dose (4 ppm in the feed) previously determined to be beneficial to other small mammals, but they found it to be detrimental to rabbits because it increased mortality during inflammatory bowel disease and/or colibacillosis infection challenges. Next, the inventors tested the supplementation of rabbits with a new lower dose of 2ppm, followed by an enteritis infection challenge, and found that at this low dose, mortality was greatly reduced. The inventors challenge colibacillosis infection after testing rabbits with a 2ppm dose, and found that mortality is greatly reduced at this dose.

Thus, dosages of capsicum oleoresin used in the present invention to improve rabbit health (reduce mortality including diarrhoea and bloating and morbidity) and performance (increase intake, daily gain and/or increase growth or feeding efficiency) include all dosages of ≤ 2ppm in the finished feed.

In the inventive process of the present invention, it was found that there is a strong synergistic effect between the high intensity sweetener and the capsicum oleoresin. In addition, when the high-sweetness sweetener with the sweetness of less than 180ppm and the capsicum oleoresin with the sweetness of 2ppm are added into the feed, the synergistic effect is strongest. When these inclusion rates were tested as a combination supplement, the health of rabbits was improved (decreased mortality including diarrhea and bloating and morbidity) and growth efficiency was also increased.

Thus, the dosage of the mixture of high intensity sweeteners and capsicum oleoresin used in the present invention for improving rabbit health (reducing mortality including diarrhoea and bloating and morbidity) and performance (increasing intake, daily gain and/or increasing growth or feeding efficiency) comprises all dosages having a high intensity sweetener content of less than or equal to 200ppm and preferably less than or equal to 180ppm and a capsicum oleoresin content of less than or equal to 2ppm (weight ratio of high intensity sweeteners to capsicum oleoresin less than or equal to 100:1 and preferably less than or equal to 25:1) in said finished feed.

Thus, the dosage of the mixture of high-intensity artificial sweetener and capsicum oleoresin used in the present invention for improving the health status (reducing mortality including diarrhea and bloating and morbidity) and performance (increasing intake, daily gain and/or increasing growth or feeding efficiency) of rabbits comprises all dosages having a high-intensity artificial sweetener content of <100ppm and preferably <50ppm and a capsicum oleoresin content of < 2ppm in the finished feed (the weight ratio of high-intensity artificial sweetener to capsicum oleoresin is < 50:1 and preferably < 25: 1).

In the course of the invention, the inventors subsequently tested the combined feeding of such low doses of high intensity sweetener and capsicum oleoresin to other mammals (including pigs and calves). In both cases, low dose feeding improved digestive health and performance in zootechnics.

The dosage of the mixture of high intensity natural sweetener and capsicum oleoresin used in the present invention to improve the health (reduce mortality including diarrhoea and bloating and morbidity) and performance (increase in intake, daily gain and/or increase in growth or feeding efficiency) of mammals includes all dosages having a high intensity natural sweetener content of less than or equal to 200ppm and preferably less than or equal to 180ppm and a capsicum oleoresin content of less than or equal to 2ppm in said finished feed (weight ratio of high intensity natural sweetener to capsicum oleoresin of less than or equal to 100:1 and preferably less than or equal to 25: 1). Examples provided herein include natural high intensity sweeteners with capsicum oleoresin in weight ratios of 12.5:1, 45:1, 90:1 (example 2), 11.5:1 (example 3), 13:1 (example 4) and 15:1 (example 5).

The inventive product comprises high intensity sweeteners and capsicum oleoresin, wherein the content of stevia extract (comprising at least 75 wt% of steviol glycosides, of which at least 25 wt% is rebaudioside a) is up to 66 wt%, and the content of capsicum oleoresin (comprising at least 6 wt% of capsaicin (capsaicin and dihydrocapsaicin)) is up to 3 wt%. Thus, the finished product comprises >49 wt% steviol glycosides, >12 wt% rebaudioside a and >0.18 wt% capsaicin. It also contains up to 3 wt% NHDC and up to 3 wt% ammonium glycyrrhizinate. The product may contain gum arabic, modified starch, maltodextrin, and other processing aids. The product may be obtained by standard atomization techniques (e.g., fluidized bed spray granulation, spray drying, etc.).

The product created by the invention contains high intensity sweetener and capsicum oleoresin, and is used for improving the health condition (reducing mortality rate including diarrhea and bloating) and the behavior (increasing intake, daily gain and/or improving growth or feeding efficiency) of mammals, and the effective dose of the product comprises all doses which are less than or equal to 100ppm in the finished feed.

The product created by the invention contains high-intensity artificial sweetener and capsicum oleoresin, and is used for improving the health condition (reducing mortality rate including diarrhea and bloating and morbidity rate) and the behavior performance (increasing the intake, daily gain and/or improving the growth or feeding efficiency) of mammals, and the effective dose of the product comprises all doses which are less than or equal to 100ppm in the finished feed.

The product created by the invention contains natural sweeteners with high sweetness and capsicum oleoresin, is used for improving the health condition (reducing mortality rate including diarrhea and bloating and morbidity rate) and the performance (increasing intake, daily gain and/or improving growth or feeding efficiency) of mammals, and comprises all dosage of less than or equal to 100ppm in the finished feed.

The high-sweetness natural sweetener in the product created by the invention can be quantitatively analyzed by measuring the stevioside level by using High Performance Liquid Chromatography (HPLC).

Quantitative analysis of capsicum oleoresin in the product created by the present invention can be performed by measuring capsaicin levels (capsaicin and dihydrocapsaicin) using HPLC or gas chromatography.

The invention is not to be limited to the details given herein, but includes variations that are within the scope of the claims.