WO2015154257A1

WO2015154257A1 - Gender specific synthetic nutritional compositions and, nutritional systems comprising them

Info

Publication number: WO2015154257A1
Application number: PCT/CN2014/074999
Authority: WO
Inventors: Michael Affolter; Sagar THAKKAR; Carlos Antonio DE CASTRO
Original assignee: Nestle China Ltd
Current assignee: Nestle China Ltd
Priority date: 2014-04-09
Filing date: 2014-04-09
Publication date: 2015-10-15
Anticipated expiration: 2016-10-09
Also published as: CN106413428A; MX389069B; RU2016143803A3; RU2016143803A; PH12016501920A1; US20170027212A1; AU2015101947A4; RU2708313C2; MX2016012423A; AU2018102084A4; EP3131415A4; EP3131415A1; AU2018102084A6; AU2015245737A1; AU2018102081A4; AU2015101947A6; WO2015154668A1; AU2018102081A6

Abstract

Gender specific synthetic nutritional compositions for infants up to 1 month of age wherein, the leucine and/or threonine and/or tyrosine content is adapted based on that found in HM produced for an infant of the same gender and age, and nutritional systems comprising them.

Description

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Title：Gender specific synthetic nutritional compositions and，nutritional systems comprising them.

Technical field：The invention relates to gender specific synthetic nutritional compositions，to nutritional systems comprising them and，to their use to provide optimised nutrition and/or one or more health benefit to an infant.

Background of the invention

Even though breastfeeding is optimal for infants，existence of certain conditions may not be in the best interests of the infant and it may contraindicate breastfaeding(AAP，2012；Lawrence， 2013).In such cases，where the sole source of nutrition is not available to the infant，alternative strategies to feed them have to be devised.Feeding infants with Synthetic nutritional compositions e.g.Infant formula is one such strategy.

The compositions of the aforementioned synthetic nutritional compositions are modeled on those of human milk.However，the composition of HM is extremely dynamic and these dynamic changes remain largely unexplored and uncharacterized.Whilst it is known that components and/or their quantities may vary depending on a variety of factors including the stage of lactation，circadian rhythms and even gender，it is not known which ofthe numerous components vary and if so how they vary e.g.by stage of lactation and/or gender.

Surprisingly it has now been identified that up to 1 month，more pa rticularly up to 2 weeks， postpartum，there is a difference in the leucine and/or th reonine and/or tyrosine concentration range found in HM depending produced by mother’s to girls in comparison to mother’s to boys. This finding stems from a cross-sectional study of HM wherein，HM samples from mothers to either boys or girls were collected at various stages postpartum and analysed.Further，it was also surprisingly found that up to 1 month，more particularly up to 2 weeks，postpartum，the mean concentration of leucine and/or th reonine and/or tyrosine in HM produced by mothers to boys was higher than that produced for mothers to girls.

Because thiese gender difference in the leucine and/or th reonine and/or tyrosine concentration in HM have never been previously identified，they are not reflected in the compositions of synthetic nutritional compositions available today.

Leucine，threonine and tyrosine are amino acids.An optimum intake of amino acids helps to ensure optimum growth and development in infants.

Optimum growth and development may be immediate and/or long term.Long term may only be evident in months or years e.g.6 months，9 months，12 months，5 yea rs，10 years，or 20 years.

Accordingly，there remains a need for gender specific synthetic nutritional compositions，and nutritional systems comprising them，having compositions within which the identified gender differences，with respectto the leucine and/or threonine and/or tyrosine concentration，found in HM up to 1 month，more pa rticularly up to 2 weeks，postpa rtum are more accurately reflected and thereby optimised.

Summary of the invention

The invention is set out in the claims.The inventors have found that the leucine and/or threonine and/or tyrosine concentration range in HM va ries up to 1 month，more particularly up to 2 weeks，postpartum depending on the gender of the mother’s infant.Inlight of this finding the inventors have developed gender specific nutritional compositions and nutritional systems comprising them，that reflect these identified gender differences.Prior to aforementioned findings the skilled person has not incentive to develop such gender specific synthetic nutritional compositions or to include them in nutritional systems.

The leucine and/or th reonine and/or tyrosine concentration in the gender specific synthetic nutritional compositions of the invention，and nutritional systems comprising them，more accu rately reflect the leucine and/orth reonine and/ortyrosine concentration in HM produced for infants of the same gender and age..In light of this and，because HM is considered optimal with respect to infant nutrition，they can provide an optimized amount of leucine and/or threonine and/or tyrosine to an infant of up to 1 month of age，more particula rly up to 2 weeks of age.

The gender specific synthetic nutritional compositions can be prepared from a gender neutral synthetic nutritional composition by measu ring out an appropriate amount of said gender neutral synthetic nutritional composition and mixing it with an additive and or diluent.

Since optimized leucine and/or th reonine and/or tyrosine intake helps to ensu re the optimum growth and development of an infant，the gender specific synthetic nutritional compositions， and nutritional systems of the invention，can also be used to treat，prevent or mitigate sub optimal growth e.g.obesity of an infant.

The gender specific synthetic nutritional composition is selected from the group consisting of： infant formula，HM fortifier，and a composition for infants that is intended to be added or diluted to human milk e.g.HM fortifier..

In addition to that set out above，the inventors have also found that the leucine and/or th reonine and/or tyrosine mean concentration in HM does not vary by gender 1 month or later postpartum，more particularly after2weeks postpartum.In light of this in addition to comprising the gender specific synthetic nutritional compositions of the inyention，the nutritional systems disclosed herein may optionally also comprise synthetic nutritional compositions for infants more than 1 month of age，more particularly more than2weeks of age， wherein，the leucine and/or th reonine and/or tyrosine concentration does not differ by gender for infants of the same age.Accordingly，the nutritional systems of the invention may also provide optimized nutrition，be used to treat，prevent or mitigate sub optimal growth e.g. obesity of an infant up to12months of age，up to9months of age，up to8months of age，up to 6 months of age.

Drawings

FIG.1is a graphical representation of the identified difference in the mean leucine concentration in HM by gender at up to2weeks(5-11days)，2weeks to1month(12-30days)，1 to2months(31to60days)，2to4months(61to120days)，and4to8months(121to240days) postpartum.

FIG.2is a graphical representation of the identified difference in the mean th reonine concentration in HM by gender at up to2weeks(5-11days)，2weeks to1month(12-30days)，1 to2months(31to60days)，2to4months(61to120days)，and4to8months(121to240days) postpartum.

FIG.3is a graphical representation ofthe identified difference in the mean tyrosine concentration in HM by gender at up to2weeks(5-11days)，2weeks to1month(12-30days)，1 to2months(31to60days)，2to4months(61to120days)，and4to8months(121to240days) postpartum.

Detailed Description

As stated herein，the inventors performed a cross sectional study evaluating the nutrient composition of HM collected from mothers at various stages of lactation(up to2weeks(5-11 days)，2weeks to1month(12-30days)，1to2months(31to60days)，2to4months(61to120 days)，and4to8months(121to240days)postpartum).The study indicated different min and max ranges for the concentration of leucine and/or th reonine and/or tyrosine by gender Surprisingly，the results of this study also indicated that that up to 1 month，more particularly up to2weeks，postpartum，there is a difference in the leucine and/or th reonine and/or tyrosine mean concentration in HM depending on the gender ofthe mother’s infant.Further details of the study，analysis techniques and results a re given in example 1.

Based on the findings of the study，the inventors have designed gender specific synthetic nutritional compositions for infants up to1month，more particularly up to2weeks，of age wherein，the leucine and/or threonine and/or tyrosine concentration is adapted based on that found in HM produced for an infant ofthe same gender and age.

The term“gender specific synthetic nutritional composition”as used herein refars to any synthetic nutritional composition，intended to be consumed by an infant that is specifically adapted to the nutritional needs ofeither a female or male enfant.

Non limiting examples ofgender specific synthetic nutritional compositions for infants from birth to4months include；infant formulae，and a composition for infants that is intended to be added or diluted with HM e.g.HM fortifier.Non limiting examples of gender specific synthetic nutritional compositions for infants from4months to12months include infant formulae，a composition for infants that is intended to be added or diluted with HM e.g.HM fortifier，or food stuffs intended for consumption by infants either alone or in combination with H M e.g. complementary foods.

The term“infant”as used herein refers to a human infant of12months of age or less.

In a first aspect of the invention there is provided a gender specific synthetic nutritional composition for an infant up to1month of age，more particularly up to2weeks of age，wherein， the leucine and/or threonine and/or tyrosine concentration is adapted based on that found in HM produced for an infant of the same gender and age.

The gender specific synthetic nutritional composition can be a male specific synthetic nutritional composition or a female specific synthetic nutritional composition for an infant up to 1 month of age，more particularly up to2weeks of age.

In an embodiment the gender specific synthetic nutritional composition is a male specific synthetic nutritional composition for an infant of up to 1 month of age，more particularly up to2 weeks of age，and comprises leucine in a concentration of 84.9to438.5，170.855to438.5，84.9 to321.7，112.57to251.99，or182.28，mg/100g and/or，threonine in a concentration of41.7to 306.2，41.7to178.08，91.765to306.2，54.39to136.85，or 95.62，mg/100g，and/or tyrosine in a concentration of 30.4to160.1，75.35to160.1，30.4to129.75，52.62to104.04，or78.33， mg/100g..

In an embodiment the gender specific synthetic nutritional composition is a female specific synthetic nutritional composition for an infant of up to1month of age，more particularly up to2 weeks of age，and comprises leucine in a concentration of92.6to352.8，92.6to260.13，92.6to 170，109.08to209.78，or159.43，mg/100gand/or， threonine in a concentration of43.6 to 229.1， 43.6to162.89，43.6to91，51.42to125.4，or87.91，mg/100g，and/or tyrosine in a concentration of 23.4to160.1，23.4to130.83，23.4to75，43.14to101.3，or72.37，mg/100g.

The concentration of leucine，threonine，or tyrosine can be measured by methods well known in the art.In particular its concentration can be measured by an amino acid analyzer(using post- column derivatisation with ninhydrin)or by a pre-column derivatisation method(i.e.using PITC or OPA/FMOC chemistry as described in Blankenship D.T.et al.(1989)Analytical Biochemistry 178：227)followed by HPLC separation and quantification.

Any source of leucine，threonine，or tyrosine known to be employed in the types of synthetic nutritional compositions disclosed herein may be comprised within the gender specific synthetic nutritional compositions ofthe invention，in particular pure synthetic leucine，threonine，or tyrosine obtained through synthesis or fermentation，or liberated from any food-grade protein source such as animal or plant proteins through hydrolysis.

The leucine，threonine，or tyrosine may be intact，hydrolysed，partially hydrolysed，or any combination thereof.

The gender specific synthetic nutritional compositions of the invention can also comprise any other ingredients or excipients known to be employed in synthetic nutritional compositions.

Non limiting examples of such ingredients include：other amino acids，proteins，carbohydrates， oligosaccharides，lipids，prebiotics or probiotics，essential fatty acids，nucleotides，nucleosides， vitamins，minerals，and other micronutrients.

Non limiting examples of other amino acids include，arginine，alanine，histidine，isoleucine， proline，valine，cysteine，glutamine，glutamic acid，glycine，serine，arginine，lysine，methionine， phenylalanine，tryptophane，asparagine，aspartic acid，and combinations thereof.

Non limiting examples of proteins include casein，alpha-lactalbumin，whey，soy protein，rice protein，corn protein，oat protein，barley protein，wheat protein，rye protein，pea protein，egg protein，sunflower seed protein，potato protein，fish protein，meat protein，lactoferrin，serum albumin，immunoglobins，and combinations thereof.

Non limiting examples of carbohydrates include lactose，saccha rose，maltodexirin，starch，and mixtures thereof

Non limiting examples of lipids include：palm olein，high oleic sunflower oil，high oleic safflower oil，canola oil，fish oil，coconut oil，bovine milk fat，or any mixtures of the foregoing

Non limiting examples of essential fatty acids include：linoleic acid(LA)，α-linolenic acid(ALA) and polyunsaturated fatty acids(PUFAs).The nutritional compositions of the invention may further contain gangliosides monosialoganglioside-3(GM3)and disialogangliosides 3(GD3)， phospholipids such as sphingomyelin，phospholipids phosphatidylcholine， phosphatidylethanolamine，phosphatidylinositol，phosphatidylserine，and combinations of the foregoing.

None limiting examples of prebiotics include：oligosaccharides optionally containing fructose， galactose，mannose；dietary fibers，in particular soluble fibers，soy fibers；inulin；or mixtures thereof.Preferred prebiotics are fructo-oligosaccharides(FOS)，galacto-oligosaccharides(GOS)， isomalto-oligosaccha rides(IMO)，xylo-oligosaccharides(XOS)，arabino-xylo oligosaccharides (AXOS)，mannan-oligosaccharides(MOS)，oligosaccharides of soy，glycosylsucrose(GS)， lactosucrose(LS)，lactulose(LA)，palatinose-oligosaccharides(PAO)，malto-oligosaccharides， gums and/or hyd rolysates thereof，pectins and/or hydrolysates thereof，and combinations of the foregoing.

Further examples of oligosaccharide are described in Wrodnigg，T.M.；Stutz，A.E.(1999)Angew. Chem.Int.Ed.38：827-828and in WO2012/069416 which is incorporated herein by reference.

Non limiting examples of probiotics include：Bifidobacterium，Lactobacillus，Lactococcus， Enterococcus，Streptococcus，Kluyveromyces，Saccharoymces，Candida，in particular selected from the group consisting of Bifidobacterium longum， Bifidobacterium lactis，Bifidobacterium animalis，Bifidobacterium breve，Bifidobacterium infantis，Bifidobacterium adolescentis， Lactobacillus acidophilus，Lactobacillus casei，Lactobacillus paracasei，Lactobacillus salivarius， Lactobacillus lactis，Lactobacillus rhamnosus，Lactobacillus johnsonii，Lactobacillus plantarum， Lactobacillus salivarius，Lactococcus lactis，Enterococcus faecium，Saccharomyces cerevisiae， Saccharomyces boulardii or mixtures thereof，preferably selected from the group consisting of Bifidobacterium longum NCC3001(ATCC BAA-999)，Bifidobacterium longum NCC2705 (CNCM I- 2618)，Bifidobacterium longum NCC490 (CNCM I-2170)，Bifidobacterium lactis NCC2818 (CNCM I-3446)，Bifidobacterium breve strain A，Lactobacillus paracasei NCC2461(CNCM I-2116)， Lactobacillus johnsonii NCC533(CNCM I-1225)，Lactobacillus rhamnosus GG(ATCC53103)， Lactobacillus rhamnosus NCC4007(CGMCC1.3724)，Enterococcus faecium SF 68(NCC2768； NCIMB10415)，and mixtures thereof.

Non limiting examples of Nucleotides include：cytidine monophosphate(CMP)，uridine monophosphate(UMP)，adenosine monophosphate(AMP)，guanosine monophosphate(GMP)， or any mixtures thereof.

Nonlimiting examples of vitamins and minerals include：vitamin A，vitamin B1，vitamin B2， vitamin B6，vitamin Bi2，vitamin E.vitamin K.vitamin C，vitamin D，folic acid，inositol，niacin， biotin，pantothenic acid，choline，calcium，phosphorous，iodine，iron，magnesium，copper，zinc， manganese，chloride，potassium，sodium，selenium，chromium，molybdenum，taurine，and L- carnitine.Minerals are usually added in salt form.

Other suitable and desirable ingredients of synthetic nutritional compositions，that may be employed in the gender specific nutritional compositions of the invention，are described in guidelines issued by the Codex Alimentarius with respect to the type of synthetic nutritional composition in question e.g.Infant formula，HM fortifier，follow on formula，and food stuffs intended for consumption by infants e.g.complementary foods.

The gender specific compositions of the invention may be prepared by methods well known in the art for preparing that type of synthetic nutritional composition e.g.infant formulae，follow on formulae，a composition for infants that is intended to be added or diluted with HM e.g.HM fortifier，and food stuffs intended for consumption by infants either alone or in combination with HM e.g.complementary foods.

An exemplary method for preparing a gender specific powdered infant formula is as follows. Amino acids(including leucine and/or threonine and/or tyrosine)and/or protein source(comprising bound leucine and/or threonine and/or tyrosine)，carbohydrate source，and fat source may be blended together in appropriate proportions.Emulsifiers maybe included in the blend.Vitamins and minerals may be added at this point but are usually added later to avoid thermal degradation.Any lipophilic vitamins，emulsifiers and the like may be dissolved into the fat source prior to blending.Water，preferably water which has been subjected to reverse osmosis，may then be mixed in to form a liquid mixture.

The liquid mixture may then be thermally treated to reduce bacterial loads.For example，the liquid mixture may be rapidly heated to a temperature in the range of about 80℃ to about1 10℃ for about5seconds to about5minutes.This may be carried out by steam injection or by heat exchanger；for example a plate heat exchanger.

The liquid mixture may then be cooled to about 60℃ to about85℃；for example by flash cooling. The liquid mixture may then be homogenised；for example in two stages at about 7 MPa to about40MPa in the first stage and about2MPa to about14MPa in the second stage.The homogenised mixture may then be further cooled to add any heat sensitive components such as vitamins and minerals.The pH and solids concentration in the homogenised mixture is conveniently standardised at this point.

The homogenised mixture can be transferred to a suitable drying apparatus such as a spray drier or freeze drier and converted to powder.The powder should have a moisture concentration in less than about3％by weight.

If it is desired probiotic(s)can be added，they may be cultured according to any suitable method and prepared for addition to the infant formula by freeze-drying or spray-drying for exanple. Alternatively，bacterial preparations can be bought from specialist suppliers such as Christian Hansen and Morinaga already prepared in a suitable form for addition to food products such as infant formula.Such bacterial preparations may be added to the gender specific powdered infant formula by dry mixing.

The gender specific compositions of the invention may also be prepared from a gender neutral synthetic nutritional composition in a method comprising；measuring out an appropriate amount of said gender neutral synthetic nutritional composition and mixing it with an additive and/or diluent e.g.water so as to arrive at a gender specific nutritional composition in accordance with the invention.

The additive may be a gender specific additive comprising caseins in a particular concentration so that when mixed with the gender neutral synthetic nutritional composition，and optionally a diluent，the resulting mixture is a gender specific synthetic nutritional composition of the invention.

The gender neutral synthetic nutritional composition can be prepared by methods well known in the art.For example，as laid out above for infant formula.

One or more of the gender specific synthetic nutritional compositions of the invention can be included in a nutritional system.

The term“nutritional system”as used herein refers to a collection of more than one synthetic nutritional composition advertised or sold as part of the same product range e.g.a collection of infant formulas sold under the same brand and adapted to the nutritional needs of infants of differing genders and/or ages.The synthetic nutritional compositions making up the nutritional system may be packaged individually e.g.in capsules or boxes.Said packages can be sold individually，grouped together e.g.wrapped by plastic film or combined in a box，or in a combination of these two ways.

The nutritional system may comprise only gender specific synthetic nutritional compositions，or it may comprise a mix of gender specific and gender neutral synthetic nutritional compositions.

The term“gender neutral”as used herein is synonymous with unisex.

In a further aspect of the present invention there is provided a nutritional system comprising at least one of the gender specific synthetic nutritional compositions of the invention.

In an embodiment the nutritional system comprises a gender specific synthetic nutritional composition for a male infant of up to1month of age，more particularly up to2weeks of age， and a gender specific synthetic nutritional composition for a male infant of up to 1 month of age， more particularly up to2weeks of age.

In an embodiment the leucine and/or threonine and/or tyrosine concentration in said male gender specific synthetic nutritional composition is higher than that of said female gender specific synthetic nutritional composition.

The leucine and/or threonine and/or tyrosine concentration in the male gender synthetic nutritional compositions may be higher by any amount.

In an embodiment the ratio of the leucine concentration between the female gender specific nutritional composition and male gender specific synthetic nutritional composition is1：4.8to1： 1.005；1：4.8to1：1.14，or1：1.2to1：1.14，and/or the threonine concentration between the female gender specific nutritional composition and male gender specific synthetic nutritional composition is1：7.1to1：1.008，1：7.1to1：1.08，or1：1.34to1：1.08，and or the tyrosine concentration between the female gender specific nutritional composition and male gender specific synthetic nutritional composition is1：6.8to1：1.004，1：6.8to1：1.08，or1：1.3to1：1.08.

In an embodiment the male gender specific synthetic nutritional composition contains345.9to 0.001，345.9to22.85，or85.7to22.85，mg/100g more leucine and/or，262.6 to 0.001，262.6to 7.71，or77.1to7.71，mg/100g more threonine，and/or136.7to0.001，136.7to5.96，or7to 5.96，mg/100g more tyrosine than the female gender specific synthetic nutritional composition.

In addition to that disclosed hereinabove，the referenced study further indicated that between 12and240days postpartum there is no difference in the leucine and/or threonine and/or tyrosine mean concentration in HM depending on the gender ofthe mother’s infant.

In another embodiment the nutritional system further comprises gender specific synthetic nutritional compositions for infants more than1month of age，in particular more than2weeks of age，wherein，the leucine and/or threonine and/or tyrosine concentration does not differ by gender for infants of the same age.

In another embodiment the nutritional system further comprises gender neutral specific synthetic nutritional compositions for infants more than1month of age，more particularly more than2weeks of age.

Non limiting examples of ages，or ranges thereof，more than1month，include：1-2mths，2mth， 2-4mths，3-6mths，4-6mths，4-8mths6-12mths，7-12mths.

The nutritional system may further comprise nutritional compositions for children older than 12months.

A gender specific synthetic nutritional composition and/or nutrition system accord ing to the invention is particularly suitable for use in a method of preparing single servings of infant formula using capsules，each capsule of which contains a unit dose of a synthetic nutritional composition in concentrated form，and which is equipped with opening means contained within the capsule to permit d raining of the reconstituted synthetic nutritional composition directly from the capsule into a receiving vessel such as a baby bottle.Such a method is described in WO2006/077259.

The different synthetic nutritional compositions，including gender specific and gender neutral synthetic nutritional compositions，which may be comprised within a nutrition system，may be packed into individual capsules and presented to the consumer in multipacks containing a sufficient number of capsules to meet the requirements of an infant of a particular age or range for one week for example.suitable capsule constructions are disclosed in WO2003/059778.

The capsules can contain the synthetic nutritional compositions，(gender specific and gender neutral)in the form of powders or concentrated liquids in both cases for reconstitution by an appropriate amount of water.Both the composition and the quantity of infant formula in the capsules may vary according to the gender and/or age of the infant.If necessary，different sizes of capsules may be provided for the preparation of infant formulas for infants of different genders and/or ages.

The gender specific synthetic nutritional compositions，or nutritional systems comprising them， better reflect the differences in the leucine and/or threonine and/or tyrosine concentration in HM found by gender at one or more stages of lactation.As stated herein，optimum leucine and/or threonine and/or tyrosine intake helps to ensu re the optimum growth and development of an infant.

In another aspect of the present invention there is provided a gender specific synthetic nutritional composition and/or nutritional system as disclosed herein for use to treat，prevent or mitigate sub optimal growth of an infant e.g.obesity.

A gender specific synthetic nutritional composition may provide an optimum amount of leucine and/or threonine and/or tyrosine，to an infant up to 1 month of age，more particularly up to 2 weeks of age.

The nutritional system may provide an optimum amount of leucine and/or th reonine and/or tyrosine，to an infant up to12months of age，up to9months of age，up to8months of age，up to6months ofage，up to1month ofage，up to2weeks of age.

In another aspect of the present invention there is provided a method for providing an optimum amount of leucine and/or threonine and/or tyrosine，to an infant of up to 1 month of age，more particularly up to2weeks of age comprising：

a)Optionally preparing a gender specific synthetic nutritional compositions according to the invention from a gender neutral synthetic nutritional composition；

b)Feeding a gender specific synthetic nutritional compositions according to the invention to an infant up to1month of age，more particula rly up to2weeks of age.

As stated herein.The gender specific synthetic nutritional compositions may be prepa red from gender neutral synthetic nutritional compositions.Accordingly，in another aspect of the present invention there is provided a kit for providing an optimized amount of leucine and/or threonine and/or tyrosine，to an infant of up to 1 month of age，more pa rticularly up to 2 week of age，the kit comprising：

a)A gender neutral synthetic n utritional composition

b)A label indicating dosage requirements for an infant so as to a rrive at a gender specific nutritional composition in accordance with the invention.

The dosage requirements may be with respect to the quantity of the gender neutral synthetic nutritional employed and/or consumption frequency e.g.4 times per day.

Sudjects included in the su rvey referenced herein were recruited from4provinces across China. Accordingly，the gender specific synthetic nutritional compositions and/or nutritional systems disclosed herein can be particularly relevant for Chinese infants，and or infants born in populations having common genetic origins and/or ethnic origins and/or common dietary habits thereto e.g.Asian，Indian，and/or Mongoloid populations.

It should be appreciated that all features ofthe present invention disclosed herein can be freely combined and that variations and modifications may be made without departing from the scope of the invention as defined in the claims.Furthermore，where known equivalents exist to specific features，such equivalents a re incorporated as if specifically referred to in this specification.

There now follows a series of non-limiting examples that serve to illustrate the invention.

Examples

Example 1

The leucine and/or th reonine and/or tyrosine concentration in HM samples collected from mothers to either male or females was analysed at various stages postpartum.The HM samples were collected as part of a cross sectional survey of HM.The study criteria is set out below：

Study population

·Number of subjects

Total540healthy subjects were en rolled，allowing a drop-out rate of10percent.They were comprised of：

-480 Lactating mothers in3cities(Beijing，Suzhou and Guangzhou)

-30mothers per city for each of the5time points(5to11days，12to30days，1to2months，2 to4months，and4to8months)

Inclusion/Exclusion criteria

·Inclusion：Healthy Chinese lactating mothers without history of acute and ch ronic diseases； exclusively breast feeding mothers du ring 4 months after delivery were enrolled.

·Exclusion：Chinese lactating mothers having history of psychopathic tendencies and having no dietary memory.

The leucine and/or th reonine and/or tyrosine concentration in the HM samples collected as part of the above detailed study were analyzed using firstly acid hydrolysis in6M hyd rochloric acid at110℃ for22hrs with phenol antioxidant in the absence of oxygen to liberate all protein- bound arginine，followed secondly by high-sensitivity amino acid analysis using derivatisation with o-Phthalaldehyde(OPA)and9-Fluorenylmethyl Chloroformate(FMOC)，and fluorescence detection(Blankenship D.T.et al.(1989)Ana/ytica/Biochemistry178：227).

The results ofthe compositional analysis ofthe HM survey，with respect to the concentration of leucine，threonine，and tyrosine are shown in table I，II and III respectively.

Table I

Table II

Table III

The results of the compositional analysis were then subject to a statistical analysis employing the following statistical model：

Concentration＝sex+timeframe+timeframe+sex：timeframe-city+ε

εreferring to the residual error and sex：timeframe referring to the interaction between these2 variables.

Table IV shows the estimates for gender differences per timeframe along with the corresponding Pvalues for leucine.

Table V shows the estimates for gender differences per timeframe along with the corresponding Pvalues for threonine.

Table VI shows the estimates for gender differences per timeframe along with the corresponding Pvalues for tyrosine.

Table IV

Table V

Table VI

A P-value inferior to0.1for a particular timeframe suggests that there is a statistically significant difference in the leucine，th reonine，or tyrosine mean concentration in HM produced for males and females infants at that specific timeframe.

As can be seen from the results in tables IV，V，and VI，a statistically significant difference in the leucine， threonine，and tyrosine mean concentration between HM p roduced for male and female infants was identified at5to11days postpartum.No statistically significant difference was identified in the mean concentration of these amino acids between HM produced for male and female infants older than2 weeks postpartum Viz.12to30days，1to2months，2to4months and4to8months.

Example 2

Examples of gender specific infant formulas are given in table XI

Table V

Example3

An example of a nutritional system in accordance with the invention is given in table Xll.

Table VI

Claims

A gender specific synthetic nutritional composition for an infant up to1month of age wherein，the concentration of leucine and/or threonine，and/or tyrosine is adapted based on that found in human milk produced for an infant of the same gender and age.
A gender specific synthetic nutritional composition according to claim1wherein，if the concentration of leucine is adapted to a male infant it is84.9to438.5，mg per100g and， if the concentration of leucine is adapted to a female infant it is92.6to352.8，mg per 100g；if the concentration ofthreonine is adapted to a male infant it is41.7to306.2，mg per100g and，if the concentration of threonine is adapted to a female infant it is43.6to 229.1，mg per100g；if the concentration of tyrosine is adapted to a male infant it is30.4 to160.1，mg per100g and，if the concentration of tyrosine is adapted to a female infant it is23.4to160.1，mg per100g；
A composition according to claim1or2wherein，the gender specific synthetic nutritional composition is selected from the groups consisting of：infant formula，and a composition for infants that is intended to be added to or diluted with human milk.
A method of preparing a composition as defined in any one of claims1to3comprising： measuring out an appropriate amount of a gender neutral synthetic nutritional composition and mixing it with a diluent and/or additive.
A nutritional system comprising a gender specific synthetic nutritional composition as defined in any one of claims1to3.
A nutritional system according to claim5comprising one gender specific synthetic nutritional composition for a male infant of up to1month of age as defined in claim1or 2and，one gender specific nutritional composition for a female infant of up to1month of age as defined in claim1or2wherein，the concentration of leucine and/or threonine and/or tyrosine in the synthetic nutritional composition for a male infant is higher than in that for the female infant.
A nutritional system according to claims5or7further comprising gender specific synthetic nutritional compositions for infants more than1month of age wherein，the concentration of leucine and/or threonine and/or tyrosine in said gender specific synthetic nutritional compositions does not differ by genderfor infants of the same age.
A nutritional system according to any one of claims5to8further comprising gender neutral synthetic nutritional compositions for infants of more than1month of age.
Use of a gender specific synthetic nutritional composition as defined in anyone of claims 1to3to provide an optimum amount of leucine and/or th reonine and/or tyrosine to an infant of up to1month of age.
A gender specific synthetic nutritional composition as defined in anyone of claims1to3 for use to treat，protect or mitigate sub optimal growth and development of an infant.
A method for providing an optimum amount of leucine and/or th reonine and/or tyrosine to an infant of up to1month of age comprising：

a.Optionally preparing a gender specific nutritional compositions as defined in any one of claims1to3from a gender neutral synthetic nutritional composition；

b.Feeding said gender specific nutritional compositions to an infant of up to1 month of age.
A nutritional system as defined in anyone of claims5to8for use to treat，protect or mitigate sub optimal growth and development of an infant..
A kit for providing an optimized amount of leucine and/or threonine and/or tyrosine to an infant of1to2months age，the kit comprising：

a.A gender neutral synthetic nutritional composition

b.A label indicating dosage requirements for a male and/or female infant so as to arrive at a gender specific nutritional composition as defined in any one of claims 1to3.