L-carnitine, chemically known as 3-hydroxy-4-(trimethylammonium)butanoate, is a quaternary ammonium compound involved in the metabolism of most mammals, plants and some bacteria.

The name defines the structure of the molecule:

• L- refers to the configuration of the carnitine molecule. In chemistry, the terms 'L-' and 'D-' are used to indicate the configuration of a molecule around a specific chiral centre. In the case of carnitine, the 'L-' form is the one that is biologically active and used in supplements and food additives.
• Carnitine is derived from the Latin 'carnus' or meat, as the compound was first isolated from meat.

In the human body, L-carnitine is synthesised from the amino acids lysine and methionine.

The synthesis process takes place in different steps:

• Preparation of epichlorohydrin. Epichlorohydrin is prepared from glycerol, a simple polyol compound, through a series of reactions involving hydrochloric acid and chlorine.
• Reaction with trimethylamine and sodium cyanide. Epichlorohydrin is reacted with trimethylamine and sodium cyanide to form an intermediate compound.
• Hydrolysis and decarboxylation. The intermediate compound undergoes hydrolysis and decarboxylation, a process involving the addition of water and the removal of a carboxyl group, to form L-carnitine.

It appears in the form of a white powder. 

What it is used for and where

It is often used as a dietary supplement for its potential benefits in weight loss, brain function, heart health and exercise performance.

Medical

Carnitine is synthesised in many eukaryotic organisms and its biosynthesis is initiated by the methylation of lysine. It plays a key role in the metabolism of fatty acids in the mitochondria (1).

Carnitine, however, is not considered an essential nutrient and is present in many foods, mainly those from animal sources.  Lysine and methionine are necessary ingredients for carnitine biosynthesis. 

All body tissues can produce deoxy-carnitine but, in humans, the enzyme that enables the hydroxylation of deoxy-carnitine to carnitine is only found in the liver, brain and kidneys (2).

Cosmetics

It performs a number of interesting acts.

Anti-static agent. Static electricity build-up has a direct influence on products and causes electrostatic adsorption. The antistatic ingredient reduces static build-up and surface resistivity on the surface of the skin and hair. 

Hair conditioning agent. A significant number of ingredients with specific and targeted purposes can co-exist in a hair shampoo: cleansers, conditioners, thickeners, mattifying agents, sequestering agents, fragrances, preservatives, special additives. However, the indispensable ingredients are the cleansers and conditioners as they are necessary and sufficient for hair cleansing and manageability. The others have commercial and non-essential accessory acts such as: appearance, perfume, colouring, etc. Hair conditioning agents have the task of increasing shine, manageability and volume, and reducing static electricity, especially after treatments such as colouring, ironing, waving, drying and brushing. They are, in practice, dispersants that may contain cationic surfactants, thickeners, emollients, polymers. The typology of hair conditioning agents includes: intensive conditioners, instant conditioners, thickening conditioners, drying conditioners. 

Surfactant - Cleansing agent. Cosmetic products used to cleanse the skin utilise the surfactant action that produces a lowering of the surface tension of the stratum corneum, facilitating the removal of dirt and impurities. 

Surfactant - Foam booster. This has the function of introducing gas bubbles into the water for a purely aesthetic factor, which does not affect the cleansing process, but only satisfies the commercial aspect of the cleanser by helping to spread the cleanser on the hair. This helps in the commercial success of a shampoo formulation. Since sebum has an inhibiting action on the bubble, more foam is produced in the event of a second shampoo.

Viscosity-increasing agent, aqueous. Since viscosity is important to increase the chemical and physical stability of the product, Viscosity Enhancing Agent, aqueous is an important dosage factor in gels, suspensions, emulsions, solutions. Increasing viscosity makes formulations less sedimentary and more homogeneously thickened. 

The most relevant studies on carnitine have been selected with a summary of their contents:

Carnitine studies

• Molecular Formula  C₇H₁₅NO₃
• Molecular Weight   161.20 g/mol
• CAS  541-15-1
• UNII     0G389FZZ9M
• EC Number  208-768-0

References____________________________________________________________________

(1) Bremer J.  Carnitine—metabolism and functions. Physiol. Rev. 1983;63:1420–80.

(2) Jacob C, Belleville F.   L-carnitine: metabolism, functions and value in pathology.  Pathol Biol (Paris). 1992 Nov;40(9):910-9.

E433 (Polysorbate 80 or Polyoxyethylene sorbitan monooleate) is a non-toxic non-ionic detergent widely used for solubilizing and emulsifying hydrophobic pharmaceuticals, cosmetics, and food additives (1).

The name describes the structure of the molecule:

• "Poly" refers to multiple repeated units of ethylene oxide in the molecule.
• "sorbate" refers to the sorbitol portion of the molecule, a type of sugar alcohol that is often used as a sweetener in food.
• "80" refers to the approximate number of repeated units of ethylene oxide in the molecule.
• The "oleate" part of the molecule is derived from oleic acid, a type of fatty acid.

The synthesis process takes place in several stages.

• Step 1: Preparation of raw materials: sorbitol, ethylene oxide and oleic acid.
• Step 2: Ethoxylation. Sorbitol reacts with ethylene oxide in a process that involves the addition of ethylene oxide to the sorbitol molecule, creating a series of repeated ethylene oxide units.
• Step 3: Esterification. Sorbitol ethoxylate is reacted with oleic acid and involves the formation of an ester bond between sorbitol ethoxylate and oleic acid, creating the final molecule Polysorbate 80.

What it is used for and where

Cosmetics

It is used as a surfactant, stabilizer and emulsifier in the composition of cosmetics and has these INCI functions:

Denaturant. The ionic or polar molecules of this ingredient included in formulations that interact with protein groups, modulate the properties of the solution to suit specific needs.

Surfactant - Cleansing agent. Cosmetic products used to cleanse the skin utilise the surface-active action that produces a lowering of the surface tension of the stratum corneum, facilitating the removal of dirt and impurities. 

Surfactant - Emulsifying agent. Emulsions are thermodynamically unstable and are used to soothe or soften the skin and emulsify, so they need a specific, stabilising ingredient. This ingredient forms a film, lowers the surface tension and makes two immiscible liquids miscible. A very important factor affecting the stability of the emulsion is the amount of the emulsifying agent. Emulsifiers have the property of reducing the oil/water or water/oil interfacial tension, improving the stability of the emulsion and also directly influencing the stability, sensory properties and surface tension of sunscreens by modulating the filmometric performance.

Food

Ingredient included in the list of European food additives such as E433 with emulsifier function and with name 

Labeled as E433 in the list of food additives.

How it is composed

The fatty acid (FA) composition of polysorbate 80 (PS80), a sorbitan oleic acid ester copolymerized with about 20mole of ethylene oxide, is typically characterized by gas chromatography. Here, an alternative method was developed. After saponification with potassium hydroxide the FA fraction was collected with liquid-liquid extraction using methyl-tert-butyl ether. HPLC in combination with a Corona® charged aerosol detector (CAD) was applied for the separation and detection. The method was fully validated in terms of specificity, repeatability, limits of quantification, linearity, range, accuracy and robustness. The characterization of 16 different PS80 batches demonstrated variability regarding their FA composition, with e.g. the amount of oleic acid ranging from 67.8±0.7% to 96.6±1.4%. Furthermore, this study identified petroselinic acid, a double-bond positional isomer to oleic acid in all batches, an FA not known to pharmacopoeias at present. In addition, 11-hydroxy-9-octadecenoic acid, an oxidation product of oleic acid was identified. Structure elucidation was performed by means of HPLC-MS/MS. In addition, the method was expanded to the evaluation of the free FAs. Having determined the entire FA composition, the acid value according to EP and USP can be calculated (2)

Medical - Studies

• Chemotherapy-induced nausea and vomiting (CINV) may occur during the acute (0-24 h) or delayed (25-120 h) phase following chemotherapy administration. The addition of a neurokinin 1 receptor antagonist to antiemetic regimens containing a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone has resulted in improved CINV prophylaxis. Due to numerous adverse events and hypersensitivity reactions associated with fosaprepitant, a commonly used neurokinin 1 receptor antagonist, there remains an unmet need for better-tolerated formulations. HTX-019, the US FDA-approved polysorbate 80- and synthetic surfactant-free aprepitant injectable emulsion, is bioequivalent to and better tolerated (fewer treatment-emergent adverse events) than fosaprepitant. HTX-019 represents a valuable alternative to fosaprepitant for CINV prophylaxis (3).

• The presence of blood‐brain barrier (BBB) greatly limits the availability of drugs and their efficacy against glioma. Focused ultrasound (FUS) can induce transient and local BBB opening for enhanced drug delivery. Here, we developed polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles (PS‐80‐PTX‐NPs, PPNP) and examined the enhanced local delivery into the brain for glioma treatment by combining with FUS. Our result showed PPNP had good stability, fast drug release rate and significant toxicity to glioma cells. Combined with FUS, PPNP showed a stronger BBB permeation efficiency both in the in vitro and in vivo BBB models. Mechanism studies revealed the disrupted tight junction, reduced P‐glycoprotein expression and ApoE‐dependent PS‐80 permeation collectively contribute to the enhanced drug delivery, resulting in significantly stronger antitumour efficacy and longer survival time in the tumour‐bearing mice. Our study provided a new strategy to efficiently and locally deliver drugs into the brain to treat glioma (4).
• Escherichia coli biotype O104:H4 recently caused the deadliest E. coli outbreak ever reported. Based on prior results, it was hypothesized that compounds inhibiting biofilm formation by O104:H4 would reduce its pathogenesis. The nonionic surfactants polysorbate 80 (PS80) and polysorbate 20 (PS20) were found to reduce biofilms by ≥ 90% at submicromolar concentrations and elicited nearly complete dispersal of preformed biofilms. PS80 did not significantly impact in vivo colonization in a mouse infection model; however, mice treated with PS80 exhibited almost no intestinal inflammation or tissue damage while untreated mice exhibited robust pathology. As PS20 and PS80 are classified as 'Generally Recognized as Safe' (GRAS) compounds by the Food and Drug Administration (FDA), these compounds have clinical potential to treat future O104:H4 outbreaks (5).

• Stenotrophomonas maltophilia is an opportunistic multiple-drug-resistant human pathogen that forms biofilms on implanted medical devices. We examined the potential inhibitory activity of polysorbate 80 and polymyxin B against S. maltophilia. A combination of subMIC polymyxin B and polysorbate 80 was the most effective inhibitor of growth and biofilm formation (6).
• In ophthalmology it is an excipient used as a lubricant in eye drops and eye pads with a mild cleansing action.
  

Safety

Polysorbate 80 has been involved in isolated cases of allergy in the form of contact dermatitis caused by topical drugs and in other cases after parenteral administration causing generalized reactions such as urticaria-angioedema and anaphylaxis (7).

The  Joint Food  and  Agriculture  Organization  of  the  United  Nations  (FAO)/World  Health Organization (WHO)Expert Committee on Food Additives (JECFA)derived an Acceptable Daily Intake (ADI) of  25mg/kg body  weight  (bw)/day  (group  ADI  for  polysorbates  20,  40,  60,  65  and  80)  and  the Scientific Committee  on  Food  (SCF) derived  a  group  ADI  of  10mg/kg  bw/day.  Small  amounts  of  polyoxyethylene sorbitansare absorbed. Similar toxicokinetics would be expected for all polysorbates based on their similarities in  structure  and  metabolic  fate.  The  acute  toxicity  is  very  low.  There  is  no  concern  regarding  genotoxicity, carcinogenicity or developmental  toxicity.  From a limited number  of studies,there  is  no  indication of reproductive  toxicity. The Panel recommended that the  maximum limits  for the  impurities of toxic elements  (arsenic, lead, cadmium  and  mercury)  in  the  EC  specification  for  polysorbates  (E432–E436)  should  be  revised  in order to ascertain that polysorbates (E432–E436) as food additives will not be a significant source of exposure to those toxic elements in food (8).

• Molecular Formula   C₃₂H₆₀O₁₀
• Molecular Weight  604.8 g/mol
• CAS  9005-65-6
• UNII   6OZP39ZG8H
• EC Number 500-019-9

Synonyms :

Tween(R) 80, Polyoxyethylene 20 sorbitan monooleate, 2-hydroxyethyl 2-deoxy-3,5-bis-O-(2-hydroxyethyl)-6-O-{2-[(9E)-octadec-9-enoyloxy]ethyl}hexofuranoside, sorbate80, Polyoxyethylene 20 sorbitan monooleate, EG Coolant, Sorbitan, mono-9-octadecenoate, poly(oxy-1,2-ethanediyl) derivs, 2-hydroxyethyl 2-deoxy-3,5-bis-O-(2-hydroxyethyl)-6-O-[2-(oleoyloxy)ethyl]hexofuranoside, 2-[2-[3,5-bis(2-hydroxyethoxy)oxolan-2-yl]-2-(2-hydroxyethoxy)ethoxy]ethyl

References______________________________________________________

(1) Narang AS, Delmarre D, Gao D. Stable drug encapsulation in micelles and microemulsions. Int J Pharm. 2007 Dec 10;345(1-2):9-25. doi: 10.1016/j.ijpharm.2007.08.057. 

Abstract. Oral absorption of hydrophobic drugs can be significantly improved using lipid-based non-particulate drug delivery systems, which avoid the dissolution step. Micellar and microemulsion systems, being the most dispersed of all, appear the most promising. While these systems show high drug entrapment and release under sink conditions, the improvement in oral drug bioavailability is often unpredictable. The formulation and drug-related biopharmaceutical aspects of these systems that govern oral absorption have been widely studied. Among these, preventing drug precipitation upon aqueous dilution could play a predominant role in many cases. Predictive ability and quick methods for assessment of such problems could be very useful to the formulators in selecting lead formulations. This review will attempt to summarize the research work that could be useful in developing these tools.

Williams, H.D.; Trevaskis, N.L.; Charman, S.A.; Shanker, R.M.; Charman, W.N.; Pouton, C.W.; Porter, C.J.H Strategies to address low drug solubility in discovery and development.   .  Pharmacol. Rev. 2013, 65, 315–499

(2) Ilko D, Braun A, Germershaus O, Meinel L, Holzgrabe U. Fatty acid composition analysis in polysorbate 80 with high performance liquid chromatography coupled to charged aerosol detection. Eur J Pharm Biopharm. 2015 Aug;94:569-74. doi: 10.1016/j.ejpb.2014.11.018.

(3) Navari RM. HTX-019: polysorbate 80- and synthetic surfactant-free neurokinin 1 receptor antagonist for chemotherapy-induced nausea and vomiting prophylaxis. Future Oncol. 2019 Jan;15(3):241-255. doi: 10.2217/fon-2018-0577.

(4) Li Y, Wu M, Zhang N, Tang C, Jiang P, Liu X, Yan F, Zheng H. Mechanisms of enhanced antiglioma efficacy of polysorbate 80-modified paclitaxel-loaded PLGA nanoparticles by focused ultrasound. J Cell Mol Med. 2018 Sep;22(9):4171-4182. doi: 10.1111/jcmm.13695. 

(5) Sloup RE, Cieza RJ, Needle DB, Abramovitch RB, Torres AG, Waters CM. Polysorbates prevent biofilm formation and pathogenesis of Escherichia coli O104:H4. Biofouling. 2016 Oct;32(9):1131-1140. doi: 10.1080/08927014.2016.1230849. 

(6) Malinowski AM, McClarty BM, Robinson C, Spear W, Sanchez M, Sparkes TC, Brooke JS. Polysorbate 80 and polymyxin B inhibit Stenotrophomonas maltophilia biofilm. Diagn Microbiol Infect Dis. 2017 Feb;87(2):154-156. doi: 10.1016/j.diagmicrobio.2016.11.008.

(7) Palacios Castaño MI, Venturini Díaz M, Lobera Labairu T, González Mahave I, Del Pozo Gil MD, Blasco Sarramián A. Anaphylaxis Due to the Excipient Polysorbate 80. J Investig Allergol Clin Immunol. 2016;26(6):394-396. doi: 10.18176/jiaci.0109.

(8) EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), 2015. Scientific Opinion on the re‐evaluation of polyoxyethylene sorbitan monolaurate (E 432), polyoxyethylene sorbitan monooleate (E 433), polyoxyethylene sorbitan monopalmitate (E 434), polyoxyethylene sorbitan monostearate (E 435) and polyoxyethylene sorbitan tristearate (E 436) as food additives. Efsa Journal, 13(7), p.4152.

Lysozyme is a lytic enzyme-type protein found in the human body (liver, spleen. saliva) eggs and other animal tissues, a peptide with antimicrobial activity.

Industrially it appears in the form of a white powder.

What it is used for and where

Food

Ingredient included in the list of European food additives as E1105 with a preservative function and is added to cheeses (e.g. grana padano) to maintain their integrity and to counteract Clostridia spp. bacteria.

Medical

It acts as an antioxidant, anti-inflammatory and antibacterial agent especially against Gram-positive and Gram-negative bacteria (1), acts as a protective agent in Alzheimer's disease (2), in the treatment of infections by Staffilococcus Aureus bacteria (3) and is an effective substitute for chlorhexidine and benzidine in the treatment of acute pharyngitis (4).

Cosmetics

Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

• Molecular Formula  C₉₉H₁₅₉N₃₇O₂₃
• Molecular Weight  2235.6
• CAS   9001-63-2   235-747-3
• UNII   
• EC number   232-620-4

References_________________________________________________________________________

(1) Vilcacundo R, Méndez P, Reyes W, Romero H, Pinto A, Carrillo W. Antibacterial Activity of Hen Egg White Lysozyme Denatured by Thermal and Chemical Treatments. Sci Pharm. 2018 Oct 30;86(4):E48. doi: 10.3390/scipharm86040048.

Abstract. The aim of this study was to increase the antibacterial spectrum of modified hen egg white lysozyme (HEWL) with thermal and chemical treatments against Gram-negative bacteria. The antibacterial activity of heat-denatured HEWL and chemical denatured HEWL against Gram-negative and Gram-positive bacteria was evaluated in 15 h of incubation tests. HEWL was denatured by heating at pH 6.0 and pH 7.0 and chemical denaturing was carried out for 1.0, 1.5, 2.0, and 4.0 h with DL-Dithiothreitol (DTT). HEWL modified by thermal and chemical treatments was characterized using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis method. Heat-denatured HEWL lytic activity against Micrococcus lysodeikticus lessened with increasing temperature and time of incubation with the chemical agent (DTT). The loss of lytic activity in modified HEWL suggests that the mechanism of action of the antibacterial activity is not dependent on the lytic activity. Thermal and chemical treatments of HEWL enabled the production of oligoforms and increased antibacterial activity over a wider spectrum. Heat-denatured HEWL at pH 6.0 and chemically-denatured HEWL increased the HEWL antibacterial spectrum against Gram-negative bacteria (Escherichia coli ATCC 25922). HEWL at 120 °C and pH 6.0 (1.0 mg/mL) inhibited 78.20% of the growth of E. coli. HEWL/DTT treatment for 4.0 h (1.0 mg/mL) inhibited 68.75% of the growth E. coli. Heat-denatured HEWL at pH 6.0 and pH 7.0 and chemically-denatured HEWL (1.0, 1.5, 2.0, and 4.0 h with DTT) were active against Gram-positive bacteria (Staphylococcus carnosus CECT 4491T). Heat-denatured and chemical-denatured HEWL caused the death of the bacteria with the destruction of the cell wall. LIVE/DEAD assays of fluorescent dye stain of the membrane cell showed membrane perturbation of bacteria after incubation with modified HEWL. The cell wall destruction was viewed using electron microscopy. The results obtained in this study suggest that heat-denatured HEWL at pH 6.0 and chemical-denatured HEWL treatments increase the HEWL antibacterial activity against Gram-negative bacteria.

(2) Helmfors L, Boman A, Civitelli L, Nath S, Sandin L, Janefjord C, McCann H, Zetterberg H, Blennow K, Halliday G, Brorsson AC, Kågedal K. Protective properties of lysozyme on β-amyloid pathology: implications for Alzheimer disease. Neurobiol Dis. 2015 Nov;83:122-33. doi: 10.1016/j.nbd.2015.08.024. 

(3) Chen, L.L., Shi, W.P., Zhang, T.D., Zhou, Y.Q., Zhao, F.Z., Ge, W.Y., Jin, X.Q., Lin, W.J., Guo, W.H. and Yin, D.C., 2022. Antibacterial activity of lysozyme-loaded cream against MRSA and promotion of scalded wound healing. International Journal of Pharmaceutics, 627, p.122200.

Abstract. Staphylococcus aureus (S. aureus) infection, especially its drug-resistant bacterial infection, is a great challenge often faced by clinicians and patients, and it is also one of the most important threats to public health. Finding a safe and effective antibacterial agent is of great significance for the prevention and treatment of S. aureus infection. Lysozyme is known to have antibacterial effects against Gram-positive bacteria including S. aureus. Here, high-quality lysozyme with a purity of more than 99% and an activity of more than 60, 000 U/mg was prepared from egg white, which showed excellent antibacterial activity against three strains of S. aureus, especially against MRSA. Furthermore, an antibacterial cream loaded with lysozyme was prepared and tested in scald wound healing. The lysozyme-loaded cream exhibited the effect of preventing wound infection and promoting wound healing on scalds, and no toxicity was found in animal organs. Overall, lysozyme showed great application potential in the prevention and treatment of infections caused by S. aureus and scalded wound healing. The most remarkable discovery in this work is the unexpectedly powerful inhibitory effect of lysozyme on the drug-resistant bacterial, especially MRSA, which is usually very difficult to deal with using normal antibacterial drugs.

(4) Golac-Guzina, N., Novaković, Z., Sarajlić, Z., Šukalo, A., Džananović, J., Glamočlija, U., Kapo, B., Čordalija, V. and Mehić, M., 2019. Comparative study of the efficacy of the lysozyme, benzydamine and chlorhexidine oral spray in the treatment of acute tonsillopharyngitis-results of a pilot study. Acta Medica Academica, 48(2), pp.140-146.

Abstract. Objective. Lysozyme is a natural antimicrobial and immunomodullatory enzyme, which is produced as a host response to infectious agents. The objective of this study was to compare the efficacy and safety of lysozyme-based versus benzydamine and chlorhexidine-based oral spray in patients with an acute tonsillopharyngitis associaated with a common cold. Patients and Methods. A prospective two-arm pilot study (lysozyme/cetylpyridinium/lidocaine spray versus: benzydamine spray—arm 1; chlorhexidine/lidocaine spray—arm 2) was conducted in the primary health care unit. Efficacy was evaluated by the patient’s self-assessment of pain, difficulty in swallowing and the throat swelling, by using the visual analog scale (VAS) at baseline and three follow-up visits. Safety was evaluated by the assessment of the frequency and severity of adverse effects. Results. Lysozyme-based spray reduced pain faster than benzydamine-based spray and slower than chlorhexidine-based spray. Lysozyme-based and chlorhexidine-based sprays similarly reduced difficulty in swallowing, but were faster than benzydamine-based spray. Similar effects on the reduction of throat swelling were seen in all treated groups. All tested products showed proper safety and were well tolerated, with no serious adverse events reported. Conclusions. The lysozyme-based oral spray was shown to be effective and safe in the reduction of pain, difficulty in swallowing and throat swelling in patients with acute tonsillopharyngitis associated with a common cold. Lysozyme-based oral spray (containing natural compound with advantages of influencing immune system and preventing recurrences) had similar activity to benzydamine and chlorhexidine-based oral antiseptic sprays. 

E967 (Xylitol) is a sugar alcohol with five carbon atoms and ethanol and water are used for its industrial extraction. It is produced naturally by mammalian metabolism.

It appears as a white crystalline powder.

What it is used for and where

Food

It is an artificial sweetener of vegetable origin that replaces sugar, labeled with the number E967 in the list of food additives, it is called "the sugar of wood"  as it is made from some types of trees and corn. It is produced by the hydrogenation of Xylose in conditions of high temperature (80-140 ° C) and high pressure (up to 50 atm) (1).

It belongs to polyalcohols that have the characteristic of contrasting with acids that affect tooth enamel. This is why it is used in chewing gum and in the food and pharmaceutical fields.

After 1960, Xylitol has become a common ingredient in sugar-free baked goods, anticorrosive toothpaste and mouthwashes, oral care products and diabetic food.

Excessive intake may cause laxative effects.

Cosmetics

Anti-sebum.  Controls and reduces emissions from the sebaceous glands, which are responsible for greasy, enlarged pores in the skin, where it occurs, particularly on the forehead, cheeks, nose and hair. Adjuvant in the treatment of acne.

Deodorant agent. When substances that give off an unpleasant odour are included in cosmetic formulations (typical examples are methyl mercaptan and hydrogen sulphide derived from garlic), deodorants attenuate or eliminate the unpleasant exhalation.

Flavoring agent. The purpose of this ingredient is to modify the solution to impart a certain flavour. Natural flavouring extracts are rather expensive, so the cosmetic and pharmaceutical industries resort to synthesised substances that have sensory characteristics mostly similar to natural flavourings or are naturally equivalent. This ingredient is isolated through chemical processes or is synthesised from chemicals. It is also referred to as Aroma.

Humectant. Hygroscopic compound used to minimise water loss in the skin and to prevent it from drying out by facilitating faster and greater absorption of water into the stratum corneum of the epidermis.  The epidermis is the most superficial of the three layers that make up human skin (epidermis, dermis and hypodermis) and is the layer that maintains hydration in all three layers. In turn, the epidermis is composed of five layers: horny, the most superficial, granular, spinous, shiny, and basal. Humectants have the ability to retain the water they attract from the air in the stratum corneum and have the function of moisturising the skin. They are best used before emollients, which are oil-based.

Skin conditioning agent -  Humectant. Humectants are hygroscopic substances used to minimise water loss in the skin and to prevent it from drying out by facilitating faster and greater absorption of water into the stratum corneum of the epidermis. The epidermis is the most superficial of the three layers that make up the human skin (epidermis, dermis and hypodermis) and is the layer that maintains hydration in all three layers. In turn, the epidermis is composed of five layers: corneum, the most superficial, lucidum, granulosum, spinosum and basale. Humectants have the ability to retain in the stratum corneum the water they attract from the air and have the function of moisturising the skin. It is better to use them before emollients that are oil-based.

Medical

It is used in the prevention of acute otitis media, respiratory diseases, parenteral nutrition, atopic dermatitis, wound repair, gastrointestinal infections, osteoporosis, anti-aging and inflammatory processes (2) and in food for diabetics.

The most relevant studies on this ingredient have been selected with a summary of their contents:
Xylitol studies

Typical commercial product characteristics Xylitol

• Molecular Formula  C₅H₁₂O₅
• Condensed Formula   HOCH₂[CH(OH)]₃CH₂OH
• Molecular Weight 152.15
• MExact Mass   152.068466
• CAS   87-99-0
• UNII VCQ006KQ1E
• IUPAC  (2S,4R)-pentane-1,2,3,4,5-pentol
• InChI=1S/C5H12O5/c6-1-3(8)5(10)4(9)2-7/h3-10H,1-2H2/t3-,4+,5?
• InChl Key      HEBKCHPVOIAQTA-NGQZWQHPSA-N
• SMILES   C(C(C(C(CO)O)O)O)O
• EC Number: 207-685-7     201-788-0
• DSSTox Substance ID: DTXSID7042514
• MDL number  MFCD00064292
• PubChem Substance ID   24902140
• Beilstein  1720523
• NACRES:  NA.25
• RTECS   ZF0800000

Synonyms: 

• Xylite
• ribitol
• D.ribitol
• D-Xylitol
• (2S,4R)-pentane-1,2,3,4,5-pentol
• 1,2,3,4,5-Pentahydroxypentane

References_________________________________________________________________________

(1) Granström TB, Izumori K, Leisola M. A rare sugar xylitol. Part II: biotechnological production and future applications of xylitol. Appl Microbiol Biotechnol. 2007

Wisniak J, Hershkowitz M, Leibowitz R, Stein S. Hydrogenation of xylose to xylitol. Ind Eng Chem Res. 1974

(2) Da Silva, S.S. and Chandel, A.K. eds., 2012. D-xylitol: fermentative production, application and commercialization. Springer Science & Business Media.

E951 (Aspartame) (L-aspartyl-L-phenylalanine methyl ester) is a chemical compound formed from aspartic acid and phenylalanine.

Industrially it occurs as a fine white powder.

What it is used for and where

Food

The history of aspartame dates back to 1965 when the American chemist and researcher James Schlatter, in an attempt to create a drug against gastric ulcer, chemically derived aspartame in an intermediate step of creating a tetrapeptide of the peptide hormones gastrin.

It is one of the most common sweeteners and on which have been focused countless scientific researches to establish the risks connected to the consumption of this product which is included in many food products: diet drinks, chewing gums, yogurt, desserts, vitamins, medicines. It is recommended to people with diabetes as a substitute of sugar. It has about 200 times the sweetening power of sugar.

In the European Union it is labeled as  E951 in the list of european food additives as a sweetener and it is considered by Efsa (European Food Safety Authority), safe for human health.

The acceptable daily intake of aspartame recommended by the FDA is 50 mg/kg per day in the United States and 40 mg/kg per day in the European Union (EFSA).

Researchers from the Schiller Institute for Integrated Science and Society, Boston, based on the 1997 toxicological studies of the Ramazzini Institute (an independent non-profit research laboratory based in Bologna) carried out on laboratory animals, concluded that aspartame is a chemical carcinogen in rodents even at the dose of 100 mg/kg body weight, a relatively low dose exposure dangerously close to the current permissible daily intake (ADI) levels in the USA and the European Union (1).

High-intensity sweeteners are considered potential organic contaminants due to their widespread use in food, drugs and healthcare products. They are introduced into the environment by different pathways and find their way into water (2).

For more information:

Aspartame studies

Typical optimal characteristics of the commercial product Aspartame

• Molecular Formula: C₁₄H₁₈N₂O₅
• Linear Formula:HOOCCH₂CH(NH₂)CONHCH(CH₂C₆H₅)COOCH₃
• Molecular Weight: 294.307 g/mol
• CAS: 22839-47-0  7421-84-3
• EC Number: 245-261-3  616-062-2
• UNIII: Z0H242BBR1
• Beilstein Registry Number:2223850
• MDL number: MFCD00002724
• PubChem Substance ID 24870725
• InChI=1S/C14H18N2O5/c1-21-14(20)11(7-9-5-3-2-4-6-9)16-13(19)10(15)8-12(17)18/h2-6,10-11H,7-8,15H2,1H3,(H,16,19)(H,17,18)/t10-,11-/m0/s1 
• InChl Key    IAOZJIPTCAWIRG-QWRGUYRKSA-N  
• SMILES    COC(=O)C(CC1=CC=CC=C1)NC(=O)C(CC(=O)O)N
• IUPAC   (3S)-3-amino-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid
• ChEBI    2877

Synonyms:

• Nutrasweet
• L-Aspartyl-L-phenylalanine methyl ester
• Asp-phe-ome
• Aspartylphenylalanine methyl ester
• Asp-Phe methyl ester
• Methyl aspartylphenylalanate
• Aspartam
• Dipeptide sweetener
• Aspartamum
• 1-Methyl N-L-alpha-aspartyl-L-phenylalanate
• Aspartamo
• 3-amino-3-[(1-methoxycarbonyl-2-phenyl-ethyl)carbamoyl]propanoic acid

References_____________________________________________________________________

(1) Landrigan PJ, Straif K. Aspartame and cancer - new evidence for causation. Environ Health. 2021 Apr 12;20(1):42. doi: 10.1186/s12940-021-00725-y. 

(2) Arbeláez P, Borrull F, Pocurull E, Marcé RM. Determination of high-intensity sweeteners in river water and wastewater by solid-phase extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2015 May 8;1393:106-14. doi: 10.1016/j.chroma.2015.03.035. 

E418 (Gellan gum) is a heteropolysaccharide, an anionic exocellular polysaccharide produced by Sphingomonas elodea in a carbohydrate fermentation process in which glucose, glucuronic acid, rhamnose and esterified acetic acid are also separately involved.

It appears in the form of a white powder.

Gellan is a natural hydrocolloid polysaccharide with thickening properties from which gellan gum is obtained, used in medical, food and in the restoration of ancient works of art, especially books.

What it is used for and where

Food

In the food industry, it is an additive listed as E418 in the European food additives list that is used as a thickener, stabiliser and emulsifier.

Cosmetics

Emulsion stabilizer. Emulsions are thermodynamically unstable. Emulsion stabilisers improve the formation and stability of single and double emulsions. It should be noted that in the structure-function relationship, molar mass plays an important role.

Viscosity Enhancing Agent - aqueous. Since viscosity is important for increasing the chemical and physical stability of the product, Viscosity Enhancing Agent acqueous is an important dosage factor in gels, suspensions, emulsions, solutions. Increasing viscosity makes formulations less sedimentary and more homogeneously thickened.

E375 or Nicotinic acid or Niacin (pyridine-3-formic acid) an organic vitamin, is also known as Vitamin B₃ , (a generic name that also includes vitamin PP, niacinamide, nicotinamide and derivatives) is one of the 8 water-soluble B-complex vitamins.

It is found in :

• muscle tissue
• fish
• meat
• chickens
• peanuts
• yeasts
• and other  

Industrially it appears in the form of a white powder.

What it is used for and where

Medical

It is important for the conversion of proteins, carbohydrates and fats into energy. 

It can reduce harmful LDL-cholesterol (which thickens and clogs the arteries), improve HDL-cholesterol values and thus reduce the risks for the cardiovascular system (1).

It also has positive indications for diabetes mellitus by bringing glycaemic values back to normal (2).

Food

Its deficiency can develop pellagra-like symptoms and is linked to a state of malnutrition. Ingredient included in the list of European food additives as E375 under the name nicotinic acid, acting as a stabiliser.

It is used in dairy products, in pasta making and in the production of maize flour.

Animal feed

Feed additive, which can improve milk production, poultry and meat quality.

Cosmetics

Skin conditioning agent - Mixed. This ingredient is responsible for modifying the condition of the skin when it is damaged or dry by reducing flaking and restoring elasticity.

Antistatic agent. Static electricity build-up has a direct influence on products and causes electrostatic adsorption. The antistatic ingredient reduces static build-up and surface resistivity on the surface of the skin and hair.

The most relevant studies on this vitamin have been selected with a summary of the contents:

Vitamin B₃ studies

• Molecular Formula    C₆H₅NO₂    C₅H₄NCOOH   HOOC₅H₄N 
• Molecular Weight   123.111 g/mol
• CAS   59-67-6
• EC Number   200-441-0
• UNII   2679MF687A
• PubChem Substance ID 329823272
• MDL number   MFCD00006391
• Beilstein Registry Number   109591

Synonyms: 

• Nicotinic Acid
• niacin
• Pyridine-3-carboxylic acid
• Pellagrin
• 3-pyridinecarboxylic acid
• Akotin
• vitamin B3
• Daskil
• 3-Carboxypyridine
• Efacin
• Enduracin
• Pelonin
• Nicodelmine
• Linic
• Niconacid
• nicamin
• Pellagramin
• nicobid
• Direktan
• nicocap
• Niaspan
• nicolar
• Nicacid
• Bionic
• Nicangin
• Diacin
• Peviton                  

References____________________________________________________________________

(1) Landray MJ, Haynes R, Armitage J. Niacin for reduction of cardiovascular risk.   N Engl J Med. 2014 Nov 13;371(20):1943-4. doi: 10.1056/NEJMc1411240.

Niacin for reduction of cardiovascular risk.
Mayer L.
N Engl J Med. 2014 Nov 13;371(20):1943. doi: 10.1056/NEJMc1411240#SA6.

Niacin for reduction of cardiovascular risk.
Santos-Gallego CG, Badimon J.
N Engl J Med. 2014 Nov 13;371(20):1943. doi: 10.1056/NEJMc1411240#SA5.

Niacin for reduction of cardiovascular risk.
van den Oever IA, Nurmohamed MT, Lems WF.
N Engl J Med. 2014 Nov 13;371(20):1942. doi: 10.1056/NEJMc1411240#SA4.

(2) Ding Y, Li Y, Wen A. Effect of niacin on lipids and glucose in patients with type 2 diabetes: A meta-analysis of randomized, controlled clinical trials.  Clin Nutr. 2014 Sep 28. pii: S0261-5614(14)00247-7. doi: 10.1016/j.clnu.2014.09.019. 

Wu L, Parhofer KG.  Diabetic dyslipidemia.  Metabolism. 2014 Aug 29. pii: S0026-0495(14)00258-3. doi: 10.1016/j.metabol.2014.08.010.