DAVID C. STEINBERG he skin is composed of two distinet areas — the epider- mis and the dermis, The epidermis consists of many layers of dead skin that are supported by the dermis. The dermis isa three-dimensional network of collagen fibers and clastin fibers surrounded by gel-like material called the ground substance.’ Ths determines the stability ofthe skin ‘The dermis accounts for most qualities we consider cos- metic, ie, the appearance ofthe skin. These include a moist, plump appearance and tautness, The aging process is there fore considered skin that is less tout, less moist, less plump, and in some areas, sagging along lines that are flexed (also known as wrinkles)? If a preparation could increase the turgor and firmness of the dermis, it would be a real “treat ment” cosmetic. We know that the ground substance is composed of muco- polysaccharides, noneollagen proteins, and water. Mucopol)= saccharides are also known as glycosaminoglycans. ‘The purpose of this paper is to review the structure, for- mation, and role of these mucopolysaccharides as wall as the benefits of applying hydrolyzed mucopolysaccharides to the skin ‘Structure of Mucopolysaccharides Mucopolysaccharides found in the dermis consist of hyal- vronic acid, chondroitin sulfates, and dermantan sulfate Theirstructures areas follows? Mucopolysaccharides are composed of hexosamines (on the right) and hexuronic acids (on the left). The molecular ‘weight of hyaluronic acid is several million while that of chondroitin sulfate Band dermantan sulfates about 40,000. ‘The haf life of hyaluronic acid is 2-4 days; that of chor- dtoitin sulfate and dermantan sulfate is 7-10 days. This indi ‘cates that mucopolysaccharides turn over in the body very rapidly compared to collagen or elastin, Production Mucopolysaccharides are produced in the body by the wel ‘known route from glucose (see Figure 1)* During dermis aging, the amount of hyaluronic acid de- creases from 70% to 30%, while chondroitin sulfate decreases from 20% to about 3%. This results in a parallel decrease in the water content as wells turgor ofthe dermis.® (COSMETIC TECHNOLOGY, February 1082 J "Figure: Production of mopolaccharids2 Role i the Dermis Research into the role of mucopolysaccharides in the der- mis is a relatively new field, In 1955, “the mention of mucopolysaccharides to collagen biochemists was likely to ‘evoke a hurt or scornful reaction.”* We now know that the functions of mucopolysaccharides are very important ‘The most important function of mucopolysaccharides is as 1 binding agent for water. Hyaluronic acid can bind from 5 mifg up to 4 L/g The gelike structure of water with smucopolysaccharides fils the space between collagen fibers ‘This is essential for maintaining the proper degree of turgor pressure and plasticity ofthe tissue * ‘The structure of mucopolysaccharides also allows them to regulate the water content of connective tissues, restrict other solutes, and act asa sieve for passage of large molecules.* The ‘anionic nature of these polymers also enables them to func- tion as ion-exchange regulators. Hyaluronic acid seems tobe most often located inthe inter- Fbcous collagen network. Dermantan sulfate is more often associated with collagen fbers.* ‘The other major function of mucopolysaccharides involves their relation to collagen. Mucopolysaccharides restrict the conversion of soluble collagen to insoluble collagen.* On aging. the catio of macopolysaccharides to collagen de- creases." Mucopolysaccharides also function as lubricants for collagen fibers? We know that the collagen fibers have a sheath of muco- polysaccharides surrounding them. When we reconstitute these fibers re of mucopolysaccharides, they are much more rigid Dermantan sulfate has not been isolated from the dermis without causing collagen degradation. Final, der- mantan sulfate has been found to inhibit maturation of cal- lagen into its insoluble form, thus increasing the amount of| insoluble collagen degraded by “collagenase.” Studies of Cosmetic Applications Ii obvious from examining the role mucopolysaecharides play in the dermis that increasing or replacing the diminish- ing amounts present will yield skin with more moisture and ‘more soluble collagen, and the collagen fibers will be more fexible. That isthe goal of treatment cosmetics. none study, two groups of rats were treated witha solution ‘of mucopolysacchatides and a blank saline solution. The re sults indicated that mucopolysaccharides had no effect on the skinof the eats." This eesult was scientifically expected, since the molecular weight is high and penetration was not expected, In the early 1960s, Laboratori Vevy, Inc., Genoa, Ttaly made commercially available « hydrolyzed mucopolysac- ccharide called laluramina (CTFA-adopted name: Hydro- lyzed Mucopolysaccharide, abbreviated HMP), This precur- sor (the smallest mucopolysaccharide molecule) was devel- ‘oped for the purpose of permitting absorption of the metabolic precursor of mucopolysaccharides through’ the skin, laluramina is a 100% active white erystalling powder that is readily soluble in wate. A. % solution has a pH of 3.5- 4.5 and a rotation after I hr of +86" (40.5). Iti nontoxic and noasenstizing, When HMPs were tested ina manner similar to the test run for mucopolysaccharides, the results indicated rapid repair of induced uleers."* ‘A second study was performed with HMPs to see if they would stimulate the biosynthesis of mucopelysaccharides, ‘This was done by radioactive tracing of HMPs in a cosmetic cream. The results showed the increase of mucopolysac- ccharides in the dermis, increased hydration of the dermis, and ‘reater elasticity of the skin! Rialdi reported on a controlled study of the application to rats ofa cosmetic cream containing MPs.) The study mea- sured the following properties: + Skin moisturization — measuring the water content of the skin + Skin tropism — measuring the rapidity of eicatrization of a standard trauma + Skin elasticity — measuring the tensile stcength of the sear tissue of a standard trauma, Thirty rats were treated twice daily with a cream con- taining HMPs, while thirty rats were treated using the same cream without HMPs. The rats were broken into three sroups, and tests were run at 10+, 20-, and 30-day intervals. The results ar listed below: Moisturization: %H,O weated ~ %H,O control x 100 % H,O control increase HO (i) after 10 days: +3% (2) after 20 days: +7%; (3) after 30 days: +8% Tropism: % increase cieatrization ecicat. treated ~ % cicat. conteol x 100 % cicat. control (1) 10 days: 23% (2) 20 days: 30%: (3) 30 days: 352. Elasticity: F treated ~ F control % increase tensile strength F control (1) 10 days: 16%: (2) 20 days: 19.5% (3) 30 days: 233. The second part of this study was done with 25 women. ‘They applied the control cream once a day for 30 days, tothe cheeks, backs of hands, and legs. They applied the control cream toone side anda blank to the other side. They were not aware of the contents of either cream, ‘After 30 days, the women were examined and evaluated by three dermatologists whoalso were unaware of the contents of| the ereams or which side was treated with which cream. They evaluated the women for four parameters: general appear- ance, moisturization, elasticity, and roughness. The results showed improvement froma minimum of 7.6% toa maximum of 41.2%, with the average being 25%. The dermatologists concluded that incorporating HMPs greatly improved overall appearance and moisturization and produced clearly postive resultsin improving elasticity and roughness."? Recently, an independent testing company conducted an- ‘other double-blind test to confirm these published results." ‘Twenty women applied diluted solutions (0.375% and 1.0% COSMETIC TECHNOLOGY, February 1982 (Gra Yeooe sannce Gard NO. 22 Pe“s Table I: Moisturizing cream. Ingredient % (CTFA Name [A Xaliin (5 90 | PEGSC.C, alkyl Nesatol 180} Glycerol Trio acids Lipocerite 80 | Trstearin Undebenzofene | 1.5 | Phenoxyethoxyparaben (and) undecylenoyl PEG-S paraben Efadermasterolol —0.02_| _Unsaponifiable soya oil Bldroramnosan | 10 Propylene alyco! 60 Isoxal H 1.2 | Isocethetb-10 stearate and) isosteareth-I0 stearate Water 450 C Fragrance 0.04) Taluramina 03 | Hydeolyzed ‘mucopolysaccharides Collagenon 20 | Soluble allagen [_ Water 614 Heat A and B to 65°C-70°C. Mix A into B wih sting Homogenize 10 min, col to 40°C. Dissolve in water, mix with | vance. Add CioAandBats0°C. Stir | Table Il: Moisturizing tonic: Ingredient % CTPA Name Propylene slycol Is Hydroessemtial rose 0.015 | Rose oil Water 87.185 Desomina 205 | Glucamine Taluramina 0.2) Hydrolyzed | mucopolysaccharides Color Loos “Mix the hydrocsenta ose withthe water wing turboemulsitier until completion of solublity. Mix the remaining ingredients Table II: Moisturizing gel Ingredient % ‘CTFA Name Taluramina 0.25 | Hydrolyzed 1 ucopolysaccharides Hydroessential chamomile | 0.01 | Chamomile il Mey! paraben} 0.1 7 Liporamnosan | 3.0 | Gelling agent Water 96.64 Dissolve the hydroessetial chamomile inthe water witha turboemlsier Add the Taluramina and methylparaben std dissolve. Finally add the Liporamaosan with sticing, Once the gel has formed, remove th ar bubbles using a vacuur. HMPs in combination with soluble collagen) twice daly for ‘one-and two-week periods. The results showed HMPs “to bea very effective and indeed superior treatment for the skin." Formulations ‘Tables I-IIT are suggested formulations for using HMPS in References. |, Pearee, RLM., and Grimmes, BJ. “The Natare of the Ground Substance.” in The Dermis, ed. Bentley, J. Peer, and Qobson, Bichard, Eugene, OR, AppictonCentury-Crafts, 1968 2 Laden, Kal, and Felger, Car. "The Struciure and Function of| Skin,” in The Chemistry and Manufacture of Cosmetics. YO. 2nd edition, ed, DeNavarre, Maison G., New York, Coatinental Press 1975, 3, Ciangheroti,S.,and Lanter, "Paste and Energetic Needs ofthe Skin." Relata Techvica, No, 18, Jan 1979, 4. Sviemai.J.A. “Organization of the Derms."n The Derm. pp. rit 4 Riad, Georgio, and Moin, Restta,"Chemisty and Biology of Mucopolysacchardes,” Relata Technica, No, 2, 1970 pp. 408- 46 6, Dorman, Albert, "Biosynthesis of Acid Mucopolysceharides, in The Dermis, pp. 123-148 1. Dunphy, 3. Eapleber. "Major Unsolved Problems: Where Do ‘We Go fom Here? in The Dermis, 293. 8. Bentley. J. Peter, “The Biological Role of the Ground Sub. sane,” in The Dero. pp. 103-119, 9. Elden, Harry, “Biophysical Aspects of Aging in Coanecive Tissue in Aging, ed- Montagna, Wiliam, Oxford, Pergamon Press, 1964, pp. 229-241 10. Gibson, T, and Kenedi,K., “The Structural Components ofthe Dermis and Their Mechanical Chatactessis,” in The Derm pp. 19-37 U1. Institute of Interdsciptinary Technology, “laluramina Col lagenon, Carbossalna: Sciemiic Cosmetology Combinations, Relata Technica, NO. 22, 1980, pp. 213. 12, Rial, Giorgio, "Experimental Evaluation of the Cutaneous Ut- lation of lauramina.” Relata Technica, No. 22,1980, pp. 9 19. 13 Rialdl, Giorgio, “Experimental Evaluation ia the Rat and in “Mano the Eutrophic Skin Effects of an O/W Cream Containing S% Callagenon and 1% laluramina.” Relara Technic, No. 24, 1980, pp. 11-20 14, Weinstein, Sidney, Report on Projet TK-I-80, NewroCommur rieation Research Laboratories, In. Danbury CT, 1980, David C Steinberg is manager of technical services for Tri-K Indus- tries, Inc, Westwood, New Jersey He has been with the company since 1978, Steinberg received a BS in chemisiry from Drexel University, Philadelphia, in 1965, and an MBA from Pace University. New York, in 1969. Hes a member of the American Chemical Soct- ‘ety, the Institute of Food Technologists, andthe Society (of Cosmetic Chemists, COSMETIC TECHNOLOGY, February 1982 "Eicle Reader Secs Cord No 23