Definition:

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OmniMixer®HMOs premix Health Benefits:

OmniMixer®HMOs premix is a type of functional raw material composed of multiple HMO monomers (such as 2'-FL, LNnT, and 3'-FL) blended in specific proportions. The technical system encompasses the entire industrial chain, from monomer production to finished product application. The primary objective is to ensure the product's functionality, stability, safety, and application compatibility.

OmniMixer®HMOs premix is functional ingredients composed of multiple HMO monomers (such as 2'-fucosyllactose 2'-FL, lactose-N-neotetraose LNnT, 3'-fucosyllactose 3'-FL, etc.) blended in specific proportions. They are widely used in infant formula foods, special medical purpose formula foods, and other fields. Due to the complex structure and high production difficulty of HMOs, strict technical measures must be implemented during the raw material and supplier control stages to ensure raw material purity, safety, consistency, and compliance.

Raw material control for OmniMixer®HMOs premix:

Product Specifications:

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Product quality standards:

● Food grade,  Infant formula, In-house

▶ Supporting early infant development

OmniMixer®HMOs premix Applications:

HMOs are the third-largest solid component after lactose and fat. OmniMixer®HMOs premix replicate the composition and proportions of key HMOs found in breast milk. This provides infants who cannot be breastfed with protection similar to that of breast milk. HMOs act as "nutritional substrates" for intestinal mucosal cells, promoting villus growth and tight junction formation. This enhances intestinal barrier integrity and reduces permeability in immature intestines. HMOs also regulate the "programming" of the infant's immune system by promoting the development of immune organs, such as the thymus and spleen, and stimulating the activity of immune cells (e.g., macrophages and T cells).

■ Supplier onboarding and dynamic management

Supplier control must ensure the reliability of raw material sources, the compliance of production processes, and the traceability of the supply chain by establishing technical standards and procedures. Richtek requires suppliers to provide documents detailing the production processes of raw materials (e.g., the source of fermentation strains and the compliance of enzyme preparations synthesized by enzymatic methods) and to verify the legality of production methods by comparing them with regulatory standards. On-site audits will be conducted based on food-grade raw material production specifications to confirm that the supplier's production environment, equipment disinfection procedures, and personnel operating specifications comply with requirements.

OmniMixer®HMOs premix is available in the following specification and contents, customized according to requirements:

☑  OmniMixer®HMOs and minerals premix

OmniMixer®HMOs premix is primarily intended for infants and young children, with the goal of bridging the gap between formula milk and breast milk. It provides nutrition and protection similar to breast milk for infants who cannot be breastfed. The mainstream application is infant formula milk, to which HMOs are added to mimic the composition and function of HMOs in breast milk. Premature infants have less-developed intestinal and immune systems, and HMO premixes can accelerate intestinal maturation and reduce the risk of necrotizing enterocolitis and sepsis. Adding low doses of HMO premixes to infant complementary foods, such as rice cereal and fruit purée, can help maintain intestinal microecological balance, particularly in infants during the weaning period or with sensitive intestines.

For populations with special needs, such as those with weakened immune systems or intestinal dysfunction, OmniMixer®HMOs premix can serve as functional ingredients that assist in disease management. Combined with probiotics and prebiotics, HMOs form synbiotic products that enhance the survival and colonization ability of probiotics, strengthening the regulation of intestinal microbiota. HMOs can serve as immune-enhancing components for sub-healthy individuals and the elderly by stimulating immune cell activity and reducing the incidence of colds and respiratory infections.

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Customized formulation capabilities for OmniMixer®HMOs premix:

The formulation design of OmniMixer®HMOs premix is a core aspect of their application, requiring consideration of breast milk similarity, functionality, safety, suitability for the target population, and regulatory compliance, involving multiple key technologies.

HMOs serve as specific nutrients for beneficial intestinal bacteria and inhibit pathogenic bacteria, thereby achieving microbial balance through bidirectional regulation. HMOs can be metabolized by beneficial bacteria, such as bifidobacteria and lactobacilli. This enables them to become dominant in the gut, thereby inhibiting the colonization of harmful bacteria. HMOs' molecular structure is similar to the glycoproteins on the surface of intestinal epithelial cells in breastfed infants. This allows HMOs to competitively bind to the adhesion proteins of pathogenic bacteria. This prevents the bacteria from adhering to the intestinal mucosa, thus reducing the risk of infectious diarrhea.

▶ Regulating the intestinal microbiota and maintaining microbial balance

Stabilisation technology for OmniMixer®HMOs premix:

The stability of OmniMixer®HMOs premix is critical to ensuring their functional efficacy. HMOs are water-soluble oligosaccharides that are susceptible to degradation (e.g., glycosidic bond breakage) or physical changes (e.g., caking, moisture absorption) due to factors such as temperature, humidity, pH, oxidation, processing, and storage conditions. During the product stability phase, which covers post-production storage, transportation, end use, and shelf life, these factors must be controlled through a series of technical measures.

■ Anti-caking and flowability optimisation technology

HMOs are highly hygroscopic and prone to caking due to particle adhesion, which affects their usability and uniformity. Physical modification is required to improve flowability. Richtek adds food-grade anti-caking agents, such as silica, tricalcium phosphate, and magnesium stearate, based on the conditions of the raw materials. These agents absorb surface moisture and increase the distance between particles, thereby reducing the probability of caking. Additionally, HMO premixes are processed into particles with a diameter of 100–300 μm via dry granulation (e.g., roller granulation). This reduces the surface area, thereby lowering the moisture absorption rate. Coating the particle surfaces with hydrophobic coatings (e.g., hydrogenated vegetable oil) can further enhance moisture resistance.

■ Degradation inhibition and antioxidant technology

To address potential oxidative and hydrolytic degradation reactions in human milk oligosaccharides (HMOs), we will inhibit the reaction process by adding additives or adjusting the system characteristics. Since HMOs are susceptible to hydrolysis in highly acidic or alkaline environments, buffering salts are added to the formulation to stabilize the premix system's pH at 6.0–7.0 (similar to breast milk pH). This reduces the likelihood of glycosidic bond hydrolysis. Additionally, we incorporate natural antioxidants to inhibit the oxidative degradation of HMOs by scavenging free radicals. If the premix contains enzymes that may degrade HMOs, such as lactase or glycosidase, we add enzyme inhibitors, such as sodium benzoate or EDTA, to suppress enzyme activity and prevent enzymatic degradation of HMOs.

■ Breast milk simulation and component ratio technology

One of the primary objectives of HMO premixes is to replicate the natural composition and ratio of HMOs found in breast milk. Therefore, Richtek's formula design is based on data from breast milk components. While over 200 types of HMOs have been identified in breast milk, the top few account for over 70% of the total content. Formula design should prioritize these "high-abundance HMOs" and reference the proportion data from different lactation stages (e.g., colostrum, transitional milk, and mature milk). For example, 2'-FL accounts for approximately 30%-50% of mature milk. Precise formulation ratios are necessary to replicate the natural active characteristics of breast milk.

The composition of HMOs in breast milk is influenced by the mother's genotype (e.g., the fucosyl transferase gene) and exhibits racial differences (e.g., 2'-FL levels are generally higher in Asian breast milk than in European or American breast milk). Therefore, formula design should incorporate breast milk data from the target market population to adjust the types of HMOs included.

HMOs enhance the body's resistance through a dual mechanism of “active defence” and “immune regulation”. In addition to inhibiting pathogen adhesion, HMOs can stimulate the secretion of mucus by the intestinal mucosa, strengthening the physical barrier; at the same time, they promote the secretion of cytokines by immune cells, enhancing the local immune response to infection. For immunocompromised populations such as preterm infants, supplementing with HMOs can reduce the incidence of sepsis and necrotising enterocolitis (NEC). HMOs can regulate the immune system's tolerance balance, reducing excessive immune responses (such as allergies to milk protein).

▶ Enhance immune defence and reduce the risk of infection and allergies

■ Raw material receiving inspection

The foundation of HMO premix quality is raw material control, which requires technical verification of the authenticity, purity, safety, and stability of raw materials. Since HMOs are diverse and some monomers have similar structures (e.g., 2'-FL and 3'-FL differ only in the position of the fucose linkage), precise technical confirmation of raw material types and structural accuracy is necessary. Richtek uses high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) to distinguish between different HMO monomers based on retention time (qualitative analysis) and characteristic ion fragments (structural confirmation). HPLC-MS/MS is the “gold standard” for HMO identification. Capillary electrophoresis (CE) leverages the charge differences between HMOs for separation, aiding in the differentiation of isomers (e.g., LNnT and LNT). In addition, we use technical means to remove contaminants (such as heavy metals, microorganisms, and chemical residues) from raw materials to ensure the safety of the raw materials used.

■ Functional synergistic design technology

The core functions of HMOs are to regulate the gut microbiota, enhance immunity, and inhibit pathogens. To maximize their efficacy, formula design must leverage synergies with other ingredients.

In formulations that include probiotics and prebiotics, HMOs can act as prebiotics, promoting the growth of beneficial bacteria, such as Bifidobacterium and Lactobacillus. Formulations must include specific probiotic strains to create a system in which HMOs and probiotics work together synergistically. In breast milk, HMOs interact with lactoferrin, nucleotides, and the milk fat globule membrane (MFGM). Formulation design must consider how these components interact with each other to avoid antagonistic interactions.

High-precision mixing technology for OmniMixer®HMOs premix:

The mixing stage of OmniMixer®HMOs premix is critical to forming a uniform, stable mixture. During this stage, HMOs are blended with carriers, anti-caking agents, and other functional ingredients (such as probiotics and nucleotides) according to the formula ratio. The objective is to achieve highly uniform dispersion of HMOs with excipients while preventing hygroscopicity, degradation, and destruction of the HMOs' physical form (e.g., caking or stratification) caused by mechanical action or environmental factors during the mixing process.

■ Optimisation of mixing process parameters

The effectiveness of mixing (uniformity and HMO stability) is directly affected by these parameters, and we achieve balance through precise control. Richtek determines critical times based on equipment type and balances mixing efficiency and material stability through speed control.

■ Mixing equipment selection and adaptation technology

The foundation for ensuring uniform mixing is selecting the appropriate mixing equipment based on the material characteristics of HMOs premix, such as particle size, density, hygroscopicity, and flowability. Horizontal screw ribbon mixers offer high mixing efficiency. For moisture-sensitive materials, these mixers can be equipped with temperature-controlled jackets and dehumidification devices to reduce moisture absorption during mixing. These mixers are ideal for HMO premixes with a high HMO content (10%-30%) or systems containing viscous excipients, such as lactose. V-type mixers have fewer dead corners, are easy to clean, and can be nitrogen-protected to prevent HMO oxidation, making them suitable for sensitive HMOs. They are ideal for low-proportion HMO premixes or systems requiring strict oxidation prevention. Conical screw mixers effectively blend materials with significant density differences and reduce stratification. Equipped with a built-in spray device, they are suitable for mixing systems that require the addition of small amounts of liquid (e.g., enzyme preparations) and are ideal for multi-component, high-density composite premixes (e.g., HMOs, probiotics, and minerals).

■ Target population-specific formulation technology

Different populations have different needs for HMOs, so formulations must be tailored accordingly. Richtek has extensive experience in this area. For example, for infants aged 0–6 months, the formulation should mimic the high HMO content found in colostrum and focus on enhancing immune protection by increasing 2'-FL and LNnT. For infants over six months, the total HMO content can be appropriately reduced while increasing HMOs that promote intestinal development (e.g., 3'-SL). Premature infants have underdeveloped intestines, so formulas should increase the proportion of HMOs (e.g., a 3:1 ratio of 2'-FL to LNnT) and reduce components that may burden the intestines. For populations at high risk for allergies, formulas can increase fucosylated HMOs (e.g., 2'-FL) to reduce allergy risk by inhibiting the adhesion of allergens to intestinal cells.

■ Microencapsulation and controlled-release technology

Encapsulating HMOs within a wall material to form microcapsule particles significantly enhances their tolerance to environmental factors while controlling their release efficiency in the final product. We select hydrophilic or amphiphilic wall materials and form microcapsules using spray drying, freeze drying, or emulsification-crosslinking methods. For liquid premixes (e.g., those used in liquid milk), liposome encapsulation technology is employed. This technology uses phospholipid bilayers to isolate HMOs from external moisture and enzymes, thereby preventing hydrolysis caused by pH fluctuations. The solubility of the wall material can be adjusted (e.g., pH-sensitive wall materials remain stable in the gastric acid environment and dissolve upon reaching the intestines to release HMOs), ensuring the efficacy of HMOs in the intestines.

■ Mixing uniformity testing and validation technology

After mixing is complete, precise testing is required to confirm uniformity and prevent functional issues caused by local concentration deviations. The “five-point sampling method” or the “layered sampling method” is used to sample all areas within the equipment, with a minimum of ten samples per batch. High-performance liquid chromatography (HPLC) is then used to determine the content of HMOs (e.g., 2'-FL and LNnT) in each sample. The coefficient of variation (CV = standard deviation/mean × 100%) is calculated. The infant formula food standard requires CV ≤5%, and high-end products must be controlled at ≤3%.

☑  OmniMixer®HMOs and probiotics premix