`
`4B
`
`LA DERMATO:
`
` |~ WENERE
`LOGI
`
`
`Editor: Lennart Juhlin, Uppsala
`
`Honorary Editor: Nils Thyresson, Uppsala
`
`Editorial Board:
`\Denmark: Jgrgen Sgndergaard, Copenhagen
`Kristian Thestrup-Pedersen, Aarhus
`Klaus Einar Andersen, Odense
`Gunhild L. Veilsgaard, Copenhagen
`Finland: Matti Hannuksela, Oulu
`Vain6 K. Havu, Turku
`Maija Horsmanheimo, Kuopio
`Kimmo Mustakallio, Helsinki
`Timo Reunala, Tampere
`Norway: Hans-Kristian Krogh, Bergen
`Georg Rajka, Oslo
`Per Thune, Oslo
`Gunnar Volden, Trondheim
`Edvard S. Falk, Tromsg
`Lars Hellgren, Umea
`Sture Lidén, Stockholm
`Halvor Moller, Malmé
`Hans Rorsman, Lund
`Gunnar Swanbeck, Gothenburg
`Anders Vahlquist, Linképing
`
`‘Sweden:
`
`Published by the Society for the Publication of
`‘Acta Dermato-Venereologica
`Distributed by
`Almavist & Wiksell International
`Stockholm, Sweden
`
`ea a ne
`iSGo Lincan Dr.
`Méadison, Wis. 52706
`
`
`
`VOL. 71.
`
`1991. NO.
`
`UCB Biopharma SPRL(IPR2019-00400)
`Exhibit 2023 Page 1
`
`UCB Biopharma SPRL (IPR2019-00400)
`Exhibit 2023 Page 1
`
`
`
`ACTA DERMATO-VENEREOLOGICA
`was founded in 1920 by Professor Johan Almkvist. Since 1969 ownership has been vested in the
`Society for Publication of Acta Dermato-Venereologica, a non-profit organization.
`
`Editor: Professor Lennart Juhlin, M.D.,
`Department of Dermatology, University
`Hospital, S-751 85 Uppsala, Sweden
`
`Correspondence concerning manuscripts
`andeditorial matters should be addressed to:
`Acta Dermato-Venereologica, Departmentof
`Dermatology, University Hospital, S-751 85
`Uppsala, Sweden
`
`Subscriptions
`Acta Dermato-Venereologica is published six
`times per annum, each issue consisting of
`approx. 96 pages. Six numbers constitute one
`volume. Price per volume SEK 620 approx.
`US$ 100,00: — incl. postage. Supplements
`free.
`
`Correspondence concerning Subscriptions,
`Distribution and Advertising should be
`addressed to: Almavist & Wiksell International
`Company, Box 638, S-101 28 Stockholm,
`Sweden
`
`Printers: AiO Print Ltd., Odense, Denmark
`
`General Information for Authors
`Acta Dermato-Venereologica publishes papers/
`reports onscientific investigations in the field
`of dermatology and Venereology. Papers may
`be submitted from any country but must be in
`acceptable English. A proviso is that no
`essential part of an article submitted may have
`been published previously or be under
`consideration for publication elsewhere.
`Important short reports less than three printed
`pages will be published with a minimumof
`delay. Papers are open for discussion or
`commentin brief Letters to the Editor. Special
`contributions as extensive feature articles,
`reviews, dissertations and proceedings may be
`published as supplements to the journal.
`
`The corresponding authoris notified ofinitial
`receipt of the manuscript. The editorial staff
`will examine the manuscript and send it to
`reviewer(s). Usually four weeks will elapse
`before authors are notified regarding
`acceptance.
`
`Authors are requested in the interest ofall
`concermedto restrict the length of articles as
`much as possible. Papers exceedingsix printed
`pages(including illustrations, tables andlist of
`references) will usually not be accepted.
`Authors will be charged for the excess pages
`and for the costofillustrations and tables
`which exceed more than 20 %of the article’s
`total area. Papers exceeding 10 printed pages
`can be printed, at the author's own expense,
`as a Supplement to the journal. Special
`instructions for the printing of supplement will
`be sent on request.
`
`Language
`Manuscripts must conform to acceptable
`English usage. Avoid laboratory slang, clinical
`jargon and colloquialisms. The S/ system must
`adhered to.
`Abbreviations should be kept to a minimum
`and, if not internationally accepted, defined at
`first mention. Pharmaceutical preparations
`should be mentioned with their generic names
`and, whenever applicable, aslo with the trade
`names and manufacturer's name in
`parentheses.
`Authors from non-English speaking countries
`should, before submitting their manuscript,
`have the text revised by an English-speaking
`person, whose name should be given on
`request.
`Linguistic revision is not the responsibility of
`the Editor. Manuscripts written in incorrect
`English or not arranged in accordance with the
`editorial praxis of this journal will not be
`considered for publication.
`
`Copyright
`Submission of a manuscript is held to imply
`that, should the work be published,all rights
`therein will pass to the Society for Publication
`of Acta Dermato-Venereologica. It is
`furthermore understood-that the paper has not
`been published elsewhere and that,if
`accepted, it will not be republished in any
`otherjournal in the same orsimilar form
`without the Editor's written consent.
`
`Arrangement of manuscript
`See instructions on back cover.
`
`©1990 The Society for the Publication of Acta Dermato-Venereologica
`ISSN 0001-5555
`
`UCB Biopharma SPRL(IPR2019-00400)
`Exhibit 2023 Page 2
`
`UCB Biopharma SPRL (IPR2019-00400)
`Exhibit 2023 Page 2
`
`
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`UCB Biopharma SPRL (IPR2019-00400)
`Exhibit 2023 Page 3
`
`
`
`Short reports
`
`149
`
`Hexylene glycol
`
`E
`2 wee
`Be 20
`S
`
`ao
`ot
`
`Fig, 1, The inhibition of the
`growth of E. coli and
`Candida albicans, and
`Streptococcus pyogenes A
`and Staphylococcus aureus,
`by propylene glycol, and
`hexylene glycol in soy broth.
`Overall, 10% hexylene
`glycol was as effective as
`30% propylene glycol (and
`30% 1,3-butylene glycol) in
`inhibiting at least 90%of
`the growth of microbes over
`-
`venenoene 0%
`weeercce
`1%
`------ 5%
`“——'
`10%
`———_ 30%
`
`j
`Propylene glycol
`
`
`|
`
`ty
`160
`2
`3.8 420
`BX 20
`z Eg
`eS
`
`ao
`ey
`was
`180
`
`=
`
`Si
`ee
`
`160 i
`
`o min 3 min 1h
`
`4
`
`h 20h
`Oo min 5 min 1h
`incubation time
`
`4h 20 b
`
`tion in tryptic soy broth was approximately 10° CFU/ml
`(colony-forming units/ml). The tubes were incubated aero-
`bically at +37°C for 20 h. The microbial growth was fol-
`lowed by subculturing a sample of 1 yl from each of the
`tubes on a blood agar plate immediately after adding the
`test organism to the medium; thereafter at 5 min, and at 1,
`4 and 20 h during the incubation.
`After overnight incubation of the plates at +37°C the
`number of colonies formed from each sample (CFU/ml)
`was calculated. All tests were carried outin triplicate.
`
`RESULTS
`
`All three glycols, PG, HG, and BG, proved anti-
`bacterial and antifungal at 30%. At lower concentra-
`tions, HG was more potent than BG and PG, the
`latter two having very similar antimicrobial proper-
`ties. The MCCvalues of BG and PGfor S.epidermi-
`dis and for Str. mitis equalled those for S. aureus and
`Pyogenic streptococcus, respectively. In Fig. 1 the
`antimicrobial effects of PG and HG against Str. pyo-
`
`genes A, S-aureus, E. coli and Candica albicans are
`shown.
`
`DISCUSSION
`
`In the present study, HG proved a more potent
`antimicrobial agent than BG and PGin vitro, a
`finding that agreed with that of Faergemann (2) who
`found HGbetter than PG, and with Faergemann &
`Frederiksson (12) who showed that the longer the
`carbon chain in glycol was, the better its antifungal
`effect. On the other hand, the finding of Harb &
`Toama (11) was that BG should be more effective
`than other polyols against common bacteria and
`yeasts.
`Because HGisless irritating than PG to human
`skin (4), it would seem to be a very promising candi-
`date for various dermatological formulations. The
`antibacterial and irritant properties of the ultimate
`
`Acta Derm Venereol (Stockh) 71
`
`UCB Biopharma SPRL(IPR2019-00400)
`Exhibit 2023 Page 4
`
`UCB Biopharma SPRL (IPR2019-00400)
`Exhibit 2023 Page 4
`
`
`
`150=Short reports
`
`products containing HG might, however, differ from
`those achieved with aqueous solutions of HG.
`
`ACKNOWLEDGEMENT
`
`Wethank Mrs Pirjo Kontiokari for her skilful bacteriolog-
`ical work.
`
`REFERENCES
`
`1. Motoyoshi K, Nozawa S, Yoshimura M, Matsuda K.
`The safety of propylene glycol and other humectants.
`Cosmetics & Toiletries 1984; 99: 83-91.
`2. Faergemann J. Thein vitro antimycoticactivity of pro-
`pane-1,2-diol, 2-methyl-2,4-pentanediol, alcolometa-
`sone dipropionate cream, and Essex cream® with the
`addition of propane-1,2-diol against st. aureus, st. epi-
`dermidis, candida alb., tr. rubrum, and pityrosporum
`orbiculare. Curr Therapeut Res 1988a; 43: 547-551.
`3. Olitzky I. Antimicrobial properties of a propylenegly-
`col based topical therapeutic agent. J Pharm Sci 1965;
`54: 787-788.
`
`4. Kinnunen T, Hannuksela M. Skin reactions to hexy-
`lene glycol. Contact Dermatitis 1989; 20: 481-485.
`5. Hannuksela M, Pirila V, Salo OP. Skin reactions to
`propylene glycol. Contact Dermatitis 1975; 1: 112-116.
`6. Hannuksela M, Férstrém L. Reactionsto peroral pro-
`pylene glycol. Contact Dermatitis 1978; 4: 41-45.
`7. Trancik RJ, Maibach HI. Propylene glycol: irritation
`or sensitization? Contact Dermatitis 1982; 8: 185-189.
`8. CIR panel. Final report on the safety assessment of
`butylene glycol, hexylene glycol, ethoxydiglycol, and
`dipropylene glycol. J Am Coll Toxicol 1985; 4: 223-—
`248.
`9. Guillot JP, Martini MC, Giaufret JY, Gonnet JF,
`Guyot JY. Safety evaluation of some humectants and
`moisturizers used in cosmetic formulations. Int J Cosm
`Sci 1982; 4: 67-80.
`10. Fisher AA. The managementof propylene glycol-sen-
`sitive patients. Cutis 1980b; 25: 24-44.
`11. Harb NA, Toama MA. Inhibitory effect of 1,3-buty-
`lene glycol on microorganisms. Drug Cosm Ind 1976;
`118: 40-137.
`12. FaergemannJ, Fredriksson T. The antimycotic activity
`in vitro of five diols. Sabouraudia 1980; 18: 287-293.
`
`Onthe Putative Mechanism of Induction and Regulation of Melanogenesis by
`L-tyrosine
`JEFF HOWE, ROBERT COSTANTINO and ANDRZEJ SLOMINSKI
`
`Department of Microbiology and Immunology, Albany Medical College, Albany and H. W. Toolan Institute for Medical
`Research, Bennington, USA
`
`The stimulation of melanogenesis by L-tyrosine in
`hamster melanomais several-fold higher than that by
`norepinephrine, epinephrine, clonidine and isoprote-
`renol and absent in the case of tyramine dopamine
`and phenylephrine. Therefore, the melanogenic ef-
`fect of L-tyrosine in hamster melanoma follows a
`different pathway than thatlinked to the activation of
`dopaminergic and adrenergic receptors.
`(Accepted September 24, 1990.)
`Acta Derm Venereol (Stockh) 1991; 71: 150-152.
`A.Slominski, Department of Microbiology and Im-
`munology, Albany Medical College, 47 New Scot-
`land Avenue, Albany, NY 12208, USA.
`
`L-tyrosine is a precursor for proteins, tyramine, cat-
`echolamines, melanin and thyroid hormones(1). In
`some pigmentary systems, L-tyrosine, besides its
`function asa precursor to melanin, can also act as an
`inducer and a regulator of the melanogenic appara-
`tus (2-6). In cultured melanomacells, L-tyrosine is
`
`Acta Derm Venereol (Stockh) 71
`
`converted to melanin, and can also be metabolized
`to catecholamines (5, 7). In addition, it has been
`reported that activation of adrenergic receptors can
`stimulate melanogenesis (8). We therefore decided
`to test whether the regulatory role of L-tyrosine in
`melanin synthesis is specific for this amino acid, or
`follows the pathwaylinkedto the activation of dopa-
`minergic or adrenergic receptors. As an experimen-
`tal model for these studies, we used Bomirski amela-
`notic hamster melanomacells, in which L-tyrosine
`can act as an inducer and regulator of the melan-
`ogenic apparatus (2, 6, 9, 10). The effect of L-tyro-
`sine was found to be dose dependent(2), and appar-
`ently unrelated to pathways linked to cyclic AMP,
`cyclic GMP,or InsP, (11).
`
`MATERIALS AND METHODS
`
`L-tyrosine, tyramine, L-dopa, dopamine, L-phenylephrine,
`clonidine, (-)isoproterenol, (-)epinephrine, (+)norepine-
`phrine were obtained from Sigma. L-(ring-3,5—3H)-tyro-
`
`UCB Biopharma SPRL(IPR2019-00400)
`Exhibit 2023 Page 5
`
`UCB Biopharma SPRL (IPR2019-00400)
`Exhibit 2023 Page 5
`
`