GB2581318A - Novel compositions - Google Patents
Novel compositions Download PDFInfo
- Publication number
- GB2581318A GB2581318A GB1819206.2A GB201819206A GB2581318A GB 2581318 A GB2581318 A GB 2581318A GB 201819206 A GB201819206 A GB 201819206A GB 2581318 A GB2581318 A GB 2581318A
- Authority
- GB
- United Kingdom
- Prior art keywords
- amount
- composition
- berberine
- zinc
- methionine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 54
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 33
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 24
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims abstract description 22
- 241000283073 Equus caballus Species 0.000 claims abstract description 16
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052802 copper Inorganic materials 0.000 claims abstract description 15
- 239000010949 copper Substances 0.000 claims abstract description 15
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims abstract description 13
- 229930182817 methionine Natural products 0.000 claims abstract description 13
- NBGQZFQREPIKMG-UHFFFAOYSA-N 3beta-hydroxy-beta-boswellic acid Natural products C1CC(O)C(C)(C(O)=O)C2CCC3(C)C4(C)CCC5(C)CCC(C)C(C)C5C4=CCC3C21C NBGQZFQREPIKMG-UHFFFAOYSA-N 0.000 claims abstract description 12
- NBGQZFQREPIKMG-PONOSELZSA-N Boswellic acid Chemical compound C1C[C@@H](O)[C@](C)(C(O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C NBGQZFQREPIKMG-PONOSELZSA-N 0.000 claims abstract description 12
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000011701 zinc Substances 0.000 claims abstract description 12
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 12
- 208000001145 Metabolic Syndrome Diseases 0.000 claims abstract description 11
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract description 11
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229940093265 berberine Drugs 0.000 claims abstract description 11
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229960002685 biotin Drugs 0.000 claims abstract description 11
- 235000020958 biotin Nutrition 0.000 claims abstract description 11
- 239000011616 biotin Substances 0.000 claims abstract description 11
- 230000002503 metabolic effect Effects 0.000 claims abstract description 10
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 239000004475 Arginine Substances 0.000 claims abstract description 8
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims abstract description 8
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 240000007551 Boswellia serrata Species 0.000 claims abstract description 5
- 235000012035 Boswellia serrata Nutrition 0.000 claims abstract description 5
- 150000003836 berberines Chemical class 0.000 claims abstract description 5
- 239000002243 precursor Substances 0.000 claims abstract description 5
- 239000011347 resin Substances 0.000 claims abstract description 5
- 229920005989 resin Polymers 0.000 claims abstract description 5
- 239000002207 metabolite Substances 0.000 claims abstract description 4
- 239000011787 zinc oxide Substances 0.000 claims abstract description 4
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 12
- 229920002670 Fructan Polymers 0.000 claims description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 241000208202 Linaceae Species 0.000 claims description 7
- 235000004431 Linum usitatissimum Nutrition 0.000 claims description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 6
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 6
- 239000011669 selenium Substances 0.000 claims description 6
- 229910052711 selenium Inorganic materials 0.000 claims description 6
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 5
- 229940081974 saccharin Drugs 0.000 claims description 5
- 235000019204 saccharin Nutrition 0.000 claims description 5
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 5
- ZFTFOHBYVDOAMH-XNOIKFDKSA-N (2r,3s,4s,5r)-5-[[(2r,3s,4s,5r)-5-[[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxymethyl]-3,4-dihydroxy-2-(hydroxymethyl)oxolan-2-yl]oxymethyl]-2-(hydroxymethyl)oxolane-2,3,4-triol Chemical class O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(OC[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 ZFTFOHBYVDOAMH-XNOIKFDKSA-N 0.000 claims description 4
- 239000000395 magnesium oxide Substances 0.000 claims description 4
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 4
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- RJFAYQIBOAGBLC-BYPYZUCNSA-N Selenium-L-methionine Chemical compound C[Se]CC[C@H](N)C(O)=O RJFAYQIBOAGBLC-BYPYZUCNSA-N 0.000 claims description 3
- RJFAYQIBOAGBLC-UHFFFAOYSA-N Selenomethionine Natural products C[Se]CCC(N)C(O)=O RJFAYQIBOAGBLC-UHFFFAOYSA-N 0.000 claims description 3
- 229930003427 Vitamin E Natural products 0.000 claims description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 3
- 229960002718 selenomethionine Drugs 0.000 claims description 3
- 229940046009 vitamin E Drugs 0.000 claims description 3
- 235000019165 vitamin E Nutrition 0.000 claims description 3
- 239000011709 vitamin E Substances 0.000 claims description 3
- 229920001202 Inulin Polymers 0.000 claims description 2
- VVYPIVJZLVJPGU-UHFFFAOYSA-L copper;2-aminoacetate Chemical compound [Cu+2].NCC([O-])=O.NCC([O-])=O VVYPIVJZLVJPGU-UHFFFAOYSA-L 0.000 claims description 2
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 claims description 2
- 229940029339 inulin Drugs 0.000 claims description 2
- 229920001542 oligosaccharide Polymers 0.000 claims 1
- 150000002742 methionines Chemical class 0.000 abstract description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 abstract 1
- 241000283086 Equidae Species 0.000 description 20
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 14
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Abstract
A composition comprising: berberine or a berberine analogue, metabolic precursor or metabolite thereof; copper in an amount of 0.4-1.0wt%; methionine or a methionine analogue thereof; arginine; boswellic acid or a Boswellia serrata extract or resin; zinc; and biotin, is provided. Preferably the composition comprises (i) 10-30wt% berberine; (ii) 0.4-1.0wt% copper; 25-50wt% methionine; (iv) 10-30wt% arginine; (v)10-30wt% boswellic acid; (vi) 1-5wt% zinc; and 0.05-0.25wt% biotin. Preferably the copper is present as glycinate and preferably the zinc is present as zinc oxide. Preferably the composition is for use in the treatment, management or prevention of equine metabolic syndrome or of insulin resistance in equids or of laminitis.
Description
NOVEL COMPOSITIONS
The present invention relates to novel compositions, in particular to novel dietary compositions for use in the treatment, management and prevention of equine metabolic syndrome (EMS).
Equine metabolic syndrome is a disease in horses which has similarities to human metabolic syndrome (Frank et al., 2010). Obesity and insulin resistance (IR) are factors shared by both syndromes (Johnson et al., 2006). The presence of, or history of, laminitis is also characteristic of the EMS phenotype (Treiber et al., 2006). Hypertriglyceridaemia (Frank et al., 2006), hyperleptinaemia (Ca rtmill et al., 2003), arterial hypertension (Bailey et al., 2008), increased systemic markers associated with obesity (Vick et al., 2007), and altered reproductive cycling (Vick et al., 2006) are also associated with EMS.
The domestication of horses has led to feeding practices that often differ significantly from the diets consumed in a natural environment. Before domestication, the genetic predisposition of "thrifty genes" conferred an evolutionary advantage. The accumulation of fat, development of transient insulin resistance and a proinflammatory state was beneficial for survival during times of limited feed availability. These changes abated when fat stores were depleted, typically at the end of winter (Johnson et al., 2006). The subsequent domestication and propensity to overfeed horses has led to year-round persistence of adipose tissue with continual insulin resistance and its associated consequences. Adipose tissue is hormonally active and produces adipokines and adipocytokines (Rasouli and Kern, 2008). More than 100 different adipokines have been identified and it is the inappropriate secretion of these products over time that results in the pathophysiological consequences of obesity (Nutley and Prins, 2005). Specific adipokines that have been implicated in EMS include leptin, adiponectin, and resistin. Adipocytokines released by the adipose tissue or from macrophages within fat are pro-inflammatory and lead to a chronic state of low-level inflammation (Wisse, 2004, Vick et al., 2007, Rasouli and Kern, 2008). Similar to humans it is suspected that specific regions of adipose tissue in horse may be more hormonally active than other regions. One area is the accumulation of adipose tissue in the crest of the neck. A neck crest scoring system (the cresty neck score) has been developed to help distinguish horses that have developed regional rather than generalised obesity (Carter et al., 2009).
Insulin resistance is caused by defective insulin signalling at the cellular level leading to defects in a range of insulin-dependent metabolic and vascular processes, including insulin-mediated glucose transport (Kashyap and Defronzo, 2007). There is a compensatory increase in insulin secretion from the pancreas. As described earlier obesity and insulin resistance are clearly linked in EMS (Frank et al., 2006, Treiber et al., 2006, van Weyenberg et al., 2008). The link between insulin resistance and obesity may be due to the adipokine-or adipocytokine-o induced down-regulation of insulin signalling pathways and/or the accumulation of intracellular lipids in insulin-sensitive tissues, such as skeletal muscle, a process termed lipotoxicity (Slawik and Vidal-Puig, 2006). Horses like humans vary in their genetic ability to develop insulin resistance. For this reason, some obese horses do not exhibit insulin resistance (Frank, 2009).
The common signalment of the equid affected with EMS is the horse or pony between 5 and 15 years of age. The most common clinical signs at presentation include laminitis and prolonged generalised or regional obesity. It has recently been shown that supraphysiologic hyperinsulinaemia can induce laminitis in horses (Asplin et al., 2007). It is postulated that physiologic hyperinsulinaemia is a significant trigger factor in the development of laminitis (Johnson et al., 2010). The underlying effect of high insulin levels on the sensitive laminae tissues of the hoof is yet to be fully elucidated, but is suspected to be mediated by disruption to insulin-mediated vasoregulatory properties (Frank et al., 2010). It is reported that insulin resistance promotes a state of vasoconstriction due to decreased endogenous production of nitrous oxide (Muniyappa et at, 2007).
The mainstay of management of EMS involves dietary modification and increasing physical activity. Pharmacological intervention may be used to enhance the response to management changes, but if used alone is unlikely to result in a successful response. Horses should be fed low quantities of non-structural carbohydrates (NSC) in order to attenuate the insulinaemic response to meals. Pasture access should be denied or tightly controlled as the digestible energy (DE) from this source is difficult to quantify and can contribute a significant amount to total daily intake. It has recently been recognised that dietary fructan, a component of many pasture types, undergoes significant hydrolysis before the large intestine, thereby contributing to the glycaemic response to a meal (Longland and Byrd, 2006). In addition equids exhibiting insulin resistance mount an insulin response to dietary fructan (Bailey et al., 2007). Non-structural carbohydrates can be calculated by adding starch and water-soluble carbohydrate (WSC) percentages and should be below 100 g/kg of dry mater (DM) intake in affected animals (Frank et al., 2010). The practice of soaking hay in cold water for 60 min to o reduce WSC cannot be relied upon to consistently remove WSC from roughage (Longland et al., 2009).
Weight loss is essential for successful management of EMS, but horses should not be starved. This may worsen insulin resistance or cause pathologic mobilisation of fat stores. Horses should be fed hay at a recommended rate of 1.5% of body weight daily for the first 30 days of management, and then further reduced to 1% of body weight daily. Those horses that exhibit insulin resistance and regional adiposity rather than generalised obesity are more challenging to manage and often require the addition of higher energy but low NSC feedstuffs, such as beet pulp or vegetable oils. It is also recommended to feed regularly spaced small meals (Frank et al., 2010).
Exercise has been clearly shown to be effective in improving insulin sensitivity in people with insulin resistance (Goodyear and Kahn, 1998, Crandall et al., 2008). A similar response to exercise has been documented in horses with insulin resistance (Pratt et al., 2006). The primary limitation to exercise in equids with EMS is the frequent episodes of laminitis.
Although the amount of exercise required to improve insulin sensitivity has been determined in humans, this is not the case in the horse (Bajpeyi et al., 2009). The current recommendations in laminitis-free equids are to begin with 2-3 exercise sessions a week of 20-30 min duration, and slowly increase both the number and intensity of sessions over time (Frank et al., 2010).
Pharmacological management of EMS includes levothyroxine sodium, insulin-sensitising drugs such as metformin, or supplements such as magnesium and chromium. Levothyroxine has been shown to induce weight loss and improve insulin sensitivity in horses over the short-and long-term without any reported adverse effects (Frank et al., 2005). There are conflicting data on metformin improvement in insulin sensitivity in horses (Vick et al., 2006). This may be due in part to the drugs apparent low bioavailability in horses (Hustace et al., 2009).
Accordingly, there is a need for alternative approaches to the treatment, management and o prevention of equine metabolic syndrome, its factors, such as insulin resistance, and their sequelea, such as laminitis.
In its broadest sense, the present invention provides a composition comprising: berberine or a berberine analogue, metabolic precursor or inetabcdite; copper in an amount. of 0.44.0 wt%; methionine or a methionine analogue; a e; boswellic acid or a Boswell:a serrata extract or resin; zinc and biotin.
Preferably, the composition comprises berberine in an amount of 10-30 wt% or a berberine analogue, metabolic precursor or metabolite in an amount equivalent to 10-30 wt% berberine.
Preferably, the.1 berin present in an amount of about 20 1%.
Preferably, the composition comprises copper in an amount of 0.4-1.0 wt%.
Preferably, the copper is present in a clelated form; optionally as copper g vcinate.
Preferably, L. e copper is present in an amount of 05-0.8 wt%, preferably 0.55-0.75 wt%, more preferably about 0.7 wt%.
Preferably, the methionine is present in an amount of 30-40 wt%, preferably about Preferably, the composition comprises methi, n amount of 25 50 wt% or a methionine analogue in an amount equivalent to 25-50 wt% methionine.
Preferably, the cornposit on corn prises arginine in an amount of 1.0-30 wt%.
Preferably, the arginine is present in an amount of about 20 wt%.
in Preferably, the composition comprises boswellic acid in an amount of 1.0-30 wt% or a Boswellia serrata extract or resin having a boswellic acid in an amount equivalent to 10-30 wt%, Preferably, the boswe lic acid is present in an amount of about 20 t%.
PrefE the composition co prises Mr in art ai77ount of Preferably, the zinc is present in an amount of 2-4 wt preferably wt%, more preferably about 2.75 wt%.
Prefe s present as zinc ions,preferably as zinc oxide.
Preferably, the composition comprises biotin in an amount of 0,05-0,25 wt%.
Preferably, the biotin is present in an amount of wt%, preferably about 0.15wt%.
Preferably, the composition further comprises Vitamin ET, selenium and/or flax.
More preferably, the composition further comprises at:east one c.)1; Vitamin E in an amount of 1000-5000iu, preferably about 2000iu; Selenium in an amount of 1-10mg, preferably 1-5mg, more preferably about 3mg, preferably as selenomethionine; and/or flax in an amount of 50-200mg, preferably about 100mg.
Preferably, the composition further comprises magnesium, preferably as magnesium oxide, sodium chloride, potassium iodide and/or saccharin, optionally as sodium saccharin.
More preferably, the composition further comprises at least one of magnesium oxide in an amount of 1000-50000mg, preferably 1000-2000mg, more !0 preferably about 1500mg, preferably as bisglycinate; sodium chloride in an amount of 10-40g, preferably 20-30g, more preferably about 25mg; potassium iodide in an amount of 0.5-3mg, preferably 1-2mg, more preferably about 1.5mg; and/or saccharin in an amount of 1000-10,000mg, preferably 3000-7000mg, more preferably about 5000mg.
in one embodiment, the present invention provides a composition comprising about 20 wt% berherine, about 107 wt% copper, about 34 wt% methionine, about 20 wt% arginine, about 20 wt% boswellic acid, about 2.7 wt% zinc and about 0.14 wt% biotin.
Preferably, the composition further comprises about 8.5 wt% Vitaminwt% selenium and about 0.7 wt% flax.
Optionally, the composition r comprises sodium saccharin an amount of about 2. wt%.
The present invention further provides a composition comprising a fructan or fructans in an amount of 50-90 wt% and a composition as defined above in an amount of 1.0-50 w Prefera tic of ir: an 0 composition as defined above is about 2:1 by weight.
Preferably, the fructan or fructans is one or more fruct saccharicles, more preferably intilin.
The presen invention also provides as composition,.. ed above for oral administration to an equid having a mass of up to about 350kg 3n a dose of about 120g per day; or for oral administration to an equid having a mass of over about 350kg in a dose of about 200g per day.
Preferably, the dose a unit dose for administration once per day.
The present invention also provides a composition as defined above for use in the treatment, management or prevention of equine metabolic syndrome or of insulin resistance in equids or of iaminitis.
The present invention also provides the use of a composition as defined above in the treatment, management or prevention of equine metabolic syndrome or of insulin resistance in equids or of laminitis.
Preferably, the use is by oral administration to an equid having a mass of up to about 350kg in a dose of about 120g per day or for oral administration to an equid having a mass of over about 350kg in a dose of about 200g per day.
More preferably, the dose, is a unit dose for administration se.Jon oric per day.
The above and other aspects of the present invention will now be described in further detail with reference to the following examples.
Example 1
The following ingredients were combined: 3000mg Berberine (as chloride salt) 100mg Chelated copper (as copper glycinate) 5000mg Methionine (as calcium salt) 3000mg Argenine 3000mg Boswellic acid (as Boswellia serrata extract) 400mg Zinc oxide !O 20mg Biotin 30g Inulin and dosed to a feed once daily. For ponies up to around 350kg, 120g are administered orally once daily (optionally, in feed) and for adult horses over about 350kg the dose is 200g, once daily (optionally, in feed).
Example 2
A composition was made as described in Example 1 with the addition of: 2000iu Vitamin E 3mg Selenium (as selenomethionine, as yeast) 100mg flax (as stabilised flax)
Examples 3 and 4
Examples 1 and 2 were repeated (as Examples 3 & 4) with the addition of 1500mg Chelated magnesium oxide (as magnesium oxide bisglycinate) 25g sodium chloride 1.5mg potassium iodide 5000mg saccharin (as sodium salt -Phytosweet) Accordingly, the present invention provides compositions suitable for use in the treatment, management and prevention of equine metabolic syndrome, of its factors, such as insulin resistance, and their sequelea, such as laminitis. The compositions of the present invention can also be used to complement weight-loss programmes of diet and exercise and to help manage a healthy weight in all horses, ponies and other equids. The compositions of the present invention increase insulin sensitivity and thereby complement the management, treatment and prevention of laminitis in both its acute and chronic forms.
References K.E. Asplin, M.N. Sillence, C.C. Pollitt, C.M. McGowan: Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies Vet. J., 174 (2007), pp. 530-535 S.R. Bailey, N.J. Menzies-Gow, P.A.Harris, J.L. Habershon-Butcher, C.Crawford, Y. Berhane, R.C. Boston, J.Elliott: Effect of dietary fructans and dexamethasone administration on the insulin response of ponies predisposed to laminitis J. Am. Vet. Med. Assoc., 231 (2007), pp. 1365-1373 S. Bajpeyi, C.J. Tanner, C.A. Slentz, B.D.Duscha, J.S. McCartney, R.C. Hickner, W.E. Kraus, J.A. Houmard: Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation J. Appl. Physiol., 106 (2009), pp. 1079-1085 S.R. Bailey, J.L. Ha bershon-Butcher, K.J.Ransom, J. Elliott, N.J. Menzies-Gow Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis Am. J. Vet. Res., 69 (2008), pp. 122-129 R.A. Carter, R.J. Geor, W. Burton Staniar, T.A. Cubitt, P.A. Harris Apparent 'adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies Vet. J., 179 (2009), pp. 204-210 J.A. Cartmill, D.L. Thompson, W.A. Storer, L.R. Gentry, N.K. Huff Endocrine responses in mares and geldings with high body condition scores grouped by high vs. low resting leptin concentrations. J. Anim. Sci., 81 (2003), pp. 2311-2321 J.P. Crandall, W.C. Knowler, S.E. Kahn, D.Marrero, J.C. Florez, G.A. Bray, S.M.Haffner, M. Hoskin, D.M. Nathan The prevention of type 2 diabetes Nat. Clin. Pract. Endocrinol. Metab., 4(2008), pp. 382-393 N. Frank, S.B. Elliott, L.E. Brandt, D.H.Keisler. Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance J. Am. Vet. Med. Assoc., 228 (2006), pp. 1383-1390 N. Frank, R.J. Geor, S.R. Bailey, A.E.Durham, P.J. Johnson Equine metabolic syndrome J. Vet. Intern. Med., 24 (2010), pp. 467-475 L.J. Goodyear, B.B. Kahn Exercise, glucose transport, and insulin sensitivity Annu. Rev. Med., 49 (1998), pp. 235-261 J.L. Hustace, A.M. Firshman, J.E. Mata Pharmacokinetics and bioavailability of metformin in horses Am. J. Vet. Res., 70 (2009), pp. 665-668 L. Nutley, J.B. Prins Fat as an endocrine organ: relationship to the metabolic syndrome Am. J. Med. Sci., 330 (2005), pp. 280-289 P.J. Johnson, S.K. Ganjam, J.R. Turk, P.R.Buff Obesity paradigm: an introduction to the emerging discipline of adipobiology American Association of Equine Practitioners 52nd Annual Convention(2006), pp. 41-50 S.R. Kashyap, R.A. Defronzo The insulin resistance syndrome: physiological considerations Diab. Vasc. Dis. Res., 4 (2007), pp. 13-19 A.C. Longland, B.M. Byrd Pasture nonstructural carbohydrates and equine laminitis J. Nutr., 136 (2006), pp. 2099S-2102S A.C. Longland, C. Barfoot, P.A. Harris Loss of water-soluble carbohydrate and soluble protein from nine different hays soaked J. Equine Vet. Sci., 29 (2009), pp. 383-384 R. Muniyappa, M. Montagnani, K.K. Koh, M.J. Quon Cardiovascular actions of insulin Endocr. Rev., 28 (2007), pp. 463-491 S.E. Pratt, R.J. Geor, L.J. McCutcheon Effects of dietary energy source and physical conditioning on insulin sensitivity and glucose tolerance in standardbred horses Equine Vet. J. Suppl., 57 (2006), pp. 9-584 N. Rasouli, P.A. Kern Adipocytokines and the metabolic complications of obesity J. Clin. Endocrinol. Metabol., 93 (2008), pp. 645-735 M. Slawik, A.J. Vidal-Puig Lipotoxicity, overnutrition and energy metabolism in ageing Ageing Res. Rev., 5 (2006), pp. 144-164 K.H. Treiber, D.S. Kronfeld, T.M. Hess, B.M. Byrd, R.K. Splan, W.B. Staniar Evaluation of genetic and metabolic predispositions and nutritional risk factors for pasture-associated laminitis in ponies J. Am. Vet. Med. Assoc., 228 (2006), pp. 1538-1545 M.M. Vick, A.A. Adams, B.A. Murphy, D.R.Sessions, D.W. Horohov, R.F. Cook, B.J.Shelton, B.P. Fitzgerald Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse J. Anim. Sci., 85 (2007), pp. 1144-1155 M.M. Vick, D.R. Sessions, B.A. Murphy, E.L. Kennedy, S.E. Reedy, B.P. Fitzgerald Obesity is associated with altered metabolic and reproductive activity in the mare: effects of metformin on insulin sensitivity and reproductive cyclicity Reprod Fertil. Dev., 18 (2006), pp. 609-617 S. van Weyen berg, M. Hesta, J. Buyse, G.P. Janssens The effect of weight loss by energy o restriction on metabolic profile and glucose tolerance in ponies J. Anim. Physiol. Anim. Nutr., 92 (2008), pp. 538-545 B.E. Wisse The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity J. Am. Soc. Nephrol., 15 (2004), pp. 2792-2800
Claims (7)
- C LA SA composition comprising: berberine or a berberine analogue, metabolic precursor or metabolite; copper in an amount of 0.4-1.0 wt%; methionine or a methionine. analogue; a rgifli boswellic acid or a Boswellia serrata extract or resin; zinc and biotin.
- 2 A composition as claimed in claims 1. comprising: berberine in an amount of 10-30 wt% or a berberine analogue, metabolic precursor or metabolite in an amount equivalent to 10-30 wt% berberine; copper in an amount of 0.4-1.0 wt%; iii methionine in an amount of 25-50 wt% or a metbionine analogue in an amount equivalent to 25 0 wt% methionine; iv) arginine in an amount of 10-30 wt%; boswellic acid in an amount of 10-30 wt% or a Boswellia serrata extract or i5 resin having a boswellic acid in an amount equivalent to 10-30 wt%; vi) zinc in an amount of 1.-5 wt;; and vii) biotin in an amount of 0.05-0.25 wt%.
- 3 A composition as claimed in claim I or claim 2 wherein the berberine p--int in an am cunt of about 20 wt%.
- 4 A composition as claimed in any one of claims 1 to 3 wherein the copper is present a chelated form; optionally as copper glycinate.
- 5 A composition as claimed in zany preceding claim wherein the copper in m amount of 0.5-0.8 wt%, preferably 0.65-0.75 wt%, more preferably about 0.7 wt%.
- 6 A composition as claimed in any preceding claim: herein the methionine is present in ran amount of 30-40 wt%, preferably about 35 wt%.A composition as claimed in any preceding claim wherein the arginine is present in an amount of about 20 wt%.8 A composition as claimed in any preceding claim wherein the boswellic acid resent in an amount of about 20 wt%.A composition as claimed in any preceding claim wherein the zinc 3.s present as zinc preferably as zinc oxide.0 10 A composition as claimed in any preceding claim wherein the zinc is presentin an amount of 2-4 wt%, preferably 2.5-3.0 wt%, more preferably about 2.75 wt%.A composition as claimed in any preceding cairn wherein the biotin is present in n amount of 0,1412 wt%, preferably about 0.1.5wt%, 12 A composition as claimed in any preceding claim further comprising at least one of: i) Vitamin E in an amount of 1000-5000iu, preferably about 2000iu; ii) Selenium in an amount of 1-10mg, preferably 1-5mg, more preferably about 3mg, preferably as selenomethionine; and/or Hi) flax in an amount of 50-200mg, preferably about 100mg.13 A composition as claimed in any preceding claim further comprising at least one of i) magnesium oxide in an amount of 1000-50000mg, preferably 1000-2000mg, more preferably about 1500mg, preferably as bisglycinate; sodium chloride in an amount of 10-40g, preferably 20-30g, more preferably about 25mg; iii) potassium iodide in an amount of 0.5-3mg, preferably 1-2mg, more preferably about 1.5mg; and/or iv) saccharin in an amount of 1000-10,000mg, preferably 3000-7000mg, more preferably about 5000mg.14 A composition as claimed in claim 1 comprising about 20 wt% berberine, about 0.7 wt% copper, about 34 wt% methionine, about 20 wt' arginine, about 20 wt% boswellic acid, about 2.7 wt% zinc and about 0:14 wt% biotin.A composition as claimed n claim 14 f; .0 *r sing about 8.5 wt% Vitamin E, anoE1t 0.02 wt% selenium and about. 0.7 wt% flax.A composition as claimed in any preceding claim further comprising saccharin in an amount of about 25 wt%.
- 7 A composition comprising a fructan or fructans in an amount of 50-90 wt% and a composition as claimed in any preceding claim in an amount of 10-50 wt%.18 A composition as claimed in claim 17 comprising a composition s claimed in any one 1 to 15 and fructan; ratio of about 1:2.19 A composition as claimed in claim 17 or claim 18 wherein the fructan or uc ns is one or more tructo-oligosaccharides, preferably inulin.20.4 composition as claimed in any one of claims 1 to 19 for oral administration to an equid having a mass of up to about 350kg in a dose of about 1.20g per day; or for oral administration to an equid having a mass of over about 350kg in a dose of about 200g per day.21 Acomposition as claimed in claim 20 wherein the dose is a unit dose for administration once per day.22 A composition as claimed in any preceding claim For use in the treatment, management or prevention of equine metabolic syndrome or of insulin resistance in equids or of iaminitis.23 Use of a composition as claimed in any one of claims 1 to 22. in the treatment, management or prevention of equine metabolic syndrome or of insulin resistance in equids or of lamiftitis.Use as claimed in ciaim 23 for oral administration to an equ d having a mass of up to in about 350kg in a dose of about 120g per day or for oral administration to an equid having a mass of over about 350kg in a dose of about 200g per day.Use as caimed in claim 24 wherein the dose is a unit dose for administration once per day.
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EP2433629A1 (en) * | 2010-09-22 | 2012-03-28 | Fraunhofer-Gesellschaft zur Förderung der Angewandten Forschung e.V. | Use of boswellic acids for the prophylaxis and/or treatment of damages and/or inflammation of the islets of Langerhans |
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EP2433629A1 (en) * | 2010-09-22 | 2012-03-28 | Fraunhofer-Gesellschaft zur Förderung der Angewandten Forschung e.V. | Use of boswellic acids for the prophylaxis and/or treatment of damages and/or inflammation of the islets of Langerhans |
Non-Patent Citations (8)
Title |
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Hormone and Metabolic Research, vol. 47, No. 6, 2015, pages 463-469 * |
http://www.***.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=2ahUKEwjYmqLhw7PiAhVBQxUIHS1TCD0QFjABegQIAxAC&url=http%3A%2F%2Fwww.lloydinc.com%2Fmedia%2Ffiler_private%2F2012%2F02%2F13%2Fdietary_management_of_the_ir_horse-kellon_wp.pdf&usg=AOvVaw0TO40JveWMENjSmVQ-hXgZ [online] 13 February 2012 * |
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The Veterinary Journal, vol. 186, No. 3, 2010, pages 282-291 * |
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IT202100028598A1 (en) * | 2021-11-10 | 2023-05-10 | Arm R&D Soc A Responsabilita Limitata Semplificata | Association of Oleuropein, Berberine and Florizin for the treatment and prevention of metabolic syndrome |
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