= = a a g a a = a Ss S a ° s a2)INTI ERNATIONAL APPLICATION PUBLIS (19) World Intellectual Property Organization International Bureau (43) International Publication Date 12 February 2009 (12.02.2009) ‘THE PATENT COOPERATION TREATY (PCT) (10) International Publication Number WO 2009/019729 Al (61) International Patent Classification: CURC 17/00 2006.01) CO3C 177245 (2006.01) CUBC 17/92 2006.01) C03C 17/30 2006.01) 21) International Application Number: PCTAT2007/000714 (22) International Filing Date: 11 October 2007 (11.10.2007) (25) Filing Language: Italian (26) Publication Language: lish (30) PHority Data PD20074A000272 3 August 2007 (03.08.2007) IT (71) Applicant (fr all designated Sates except US): NUOVA, OMPI S.RL, [II/IT]; Via Molinella, 17, 135014 Piom- bino Dese (IT, 2) 78) Inventors; and Inventors/Applicants (for US only): CARTA, Glovannt {IAT}; c/o Noova Ompi Sx. Via Motnella, 17, -35014 Piombino Dese (IT). NICOLETTI, Fabiano [IT/T]; eo Nuova Ompi S.cl, Via Motinels, 17, 135014 Piombino Dese (T). ROSSETTO, Gilberto [ITNT]; eo Nuova ‘Ompi Sel, Via Molinell, 17, 1-35014 Piombino Dese (11), ZANELLA, Pierino (IT/1T); clo Nuova Ompi Sl. Via Motinela, 17, 35014 Piombino Dese (IT). Agent: BENETTIN, Maurizio; Via Sorio, 116, 1.35141 Padova (ID) my (81) Designated States (unless otherwise indicated, for every ind of national protection available): ME, AG, AL. AM, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, CH. CN, CO, CR, CU,CZ, DE, DK, DM, DO, DZ, EC, EE, E BS, FI, GB, GD, GE, GH, GM, GT HN, HR, HU, ID, IL, IN, IS. JP. KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK. LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PHL, PL PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, TH, TM,TN, TR, TT 17, UA, UG, US, UZ, VC, YN. ZA, MN. Designated States (unless otherwise indicated, for every kind of regional protection available: ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, 82, TZ, UG, 2M. ZW), Burasian (AM, AZ, BY, KG, KZ, MD, RU, TI, TMD. European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, Fl FR, GB, GR, HU, If, 1S, 11, LT, LU, LV, MC, MT, NL, PL PT, RO, SE, SI, SK, TR), OAPI (BF. BJ, CF, CG, CI, CM, GA, GN, GQ. GW, ML, MR, NE, SN, TD, T@) Published: ‘wth international search report (G4) Title: PROCESS FOR MANUFACTURING GLASS CONTAINERS AND PRODUCT OBTAINED THEREWITH (57) Absten he invention i a new proces for manufacturing elass containers completely o partly treated with the chemical ‘vapor deposition (CVD) technique, by which a layer of exides of Si andlor B andor andor 2 andlor‘Ta andor Al andor mixtures ‘of one or more of said elements deposited with HTAP- MOCVD technique, wherein suid deposition i caried out during the nneal- ing of the container itso, by supplying into the annealing furnace a suitable gas mixture of precursor, reactant and transport gas20 eo WO 2009019729 TITLE PROCESS FOR MANUFACTURING GLASS CONTAINERS AND PRODUCT OBTAINED THEREWITH DESCRIPTION The present patent concems the processes for manufacturing glass containers for pharmaceutical, cosmetic, diagnostic uses and in particular it concerns a new process for manufacturing glass containers with the MOCVD (Metal Organic Chemical Vapor Deposition) technique and the product obtained therewith. State of the art For preserving pharmaceutical, cosmetic or diagnostic solutions different types of containers are used, preferably made of glass, like vials, bottles, cartridges and syringes. It is known that the solutions contained in glass containers interact with the inner glass surface. The interaction that takes place determines first of all the leaching of alkaline elements from the glass surface due to the solution contained therein Said leaching may cause an undesired increase in the PH value of the solution and furthermore the ions released by glass may partially interact with some active ingredients of the products contained, thus making them inactive. In order to solve these problems, particular techniques are employed, involving the chemical deposition of low yield “protective” layers on the inner surface of said containers. Among these techniques, those known under the CVD (Chemical Vapor Deposition) or PE-CVD (Plasma Enhanced-CVD) acronym, also in its PICCVD (Plasma Impulse-CVD) variant, involve the use of PCT/IT2007/00071420 WO 20097019729 a gas mixture that, when it reaches certain pressure or temperature values or is activated by plasma in such a way as to cause suitable chemical reactions, allows layers, mainly oxide layers, to be deposited on the surface to be covered In the known processes for the production of glass containers, chemical vapor deposition (CVD) takes place in one or more specific stages after the container forming and annealing stages. For example, it is known that the common glass bottles for use in the pharmaceutical sector are mainly produced by hot processing of neutral glass tube: the end of the tube is first heated until the glass becomes malleable and formed in such a way as to obtain the neck of the bottle; successively the glass tube is flame-cut at a proper distance from the mouth in order to obtain the bottom of the bottle The latter is then annealed, in order to eliminate all of the permanent stresses created during the forming process, and finally it is packed for transfer to another plant. The PE-CVD or PI-CVD techniques, in fact, require the use of specifically dedicated rooms, systems and equipment, which consequently involves further costs for investments, materials, operation, maintenance and labour. Summary of the invention The new process for manufacturing glass containers requires the application of the MOCVD (Metal Organic Chemical Vapor Deposition) technique for the deposition of a low yield layer on the whole or at least part of the inner surface of the container, and wherein said MOCVD technique is applied within the production line and in particular during the container annealing stage, thus PCT/T2007/00071410 20 25 WO 20097019729 optimizing hourly production and costs for investments, materials, equipment, maintenance and labour. The main object of the present invention, in fact, is to carry out in the same production line the container forming stage, the appplication of said MOCVD technique and the annealing of the container, with slight modifications to the already existing and known production lines commonly used for manufacturing glass containers without low yield inner layers. In this way it is possible to use the already existing systems and equipment, inserting only the chemical vapor deposition (CVD) segment associated with the container stage, thus exploiting also the thermal energy developed during the annealing stage. A further important object of the present invention is to produce a glass container for preserving pharmaceutical, cosmetic or diagnostic solutions where the quantity of ions leached from glass through the solutions is reduced to the minimum and which substantially behaves as an inert barrier vis-a-vis those solutions. The glass container obtained with the new process is characterized in that all or at least part of its inner surface is covered by a layer of oxides of Si, B, Ti, Zr, Ta, Al and/or mixtures of these elements, applied with the MOCVD (Metal Organic Chemical Vapor Deposition) technique under high pressure and temperature conditions, during the normal manufacturing process of the glass container. Detailed description of the invention The inner surface of the new glass container obtained by means of the new process described and claimed here below is covered by a layer of oxides of Si, B, Ti, Zr, Ta, Al and/or mixtures of these PCT/T2007/00071425 WO 20097019729 elements. Said layer is obtained by means of the HTAP-MOCVD [High Temperature and Atmospheric Pressure Metal Organic Chemical Vapor Deposition] technique. This technique allows a hard layer to be chemically created on the inner surface of the glass container through the thermal decomposition, in vapor phase, of a suitable volatile metal-organic precursor. The energy required for the dissociation of the gas precursor is obtained through proper heating A glass container with layers produced according to this technique features exceptional resistance to leaching and thus behaves in a highly inert manner vis-d-vis the solutions preserved therein. Layers of oxides, mainly SiO; oxides, are particularly suitable for this purpose. The precursors that can be successfully used in this case are compounds with general formula as follows: [RoNJ,SiX;n where R = alkyl groups and X = H, halogen, alkoxy (OR’) and alkyl groups, in particular tri(dimethylamino)silane, [(CHs),N];SiH, thermostatically controlled at a temperature (30°C) suitable for ensuring effective evaporation and thermal stability. In this case, for example, deposition takes place at atmospheric pressure in a hot-wall CVD reactor, provided with a Pyrex tube (2=50 mm) heated via a tubular electric furnace. The transport gas is Nz of electronic grade (flow rate = 50 sccm) passing through a bubbler containing the precursor, that is, for example, said tri(dimethylamino)silane The reactant gas (02 of electronic grade + vapor) is introduced in the main flow in the vicinity of the reaction area, with a flow rate of 150 PCT/T2007/000714WO 2009/019729 PCTAT2007/000714 sccm, The Oz-H,0 mixture is obtained by making the oxygen bubble in a 500 cc baloon containing 250 cc of distilled water maintained at a temperature of approximately 30°C. The deposition temperature depends on the composition of the glass 5 in question, while the thickness of the layer depends on both deposition temperature and deposition time. The resulting layer of silicon dioxide deposited on the inner surface of the container adheres perfectly to it and behaves as an inert barrier to chemical etching. 10 According to the above description, it is possible, for example, to obtain a layer of SiO2 approx. 150 nm thick using borosilicate glass, with deposition temperature of 570°C and deposition time of 150 seconds, The characteristic and the main advantage of the new process with Is MOCVD technique under high pressure and temperature conditions lies in that, differently from the other known processes, it can be easily applied to any line or industrial process for manufacturing glass containers, with no need to modify it In fact, a glass container manufacturing process necessarily 20 comprises a furnace, called annealing furnace, where the container is kept at high temperature (annealing temperature) for the time necessary to reduce its stresses. During this stage the container can be supplied, in different manners and for the necessary time, with a suitable mixture of precursor, 25 reactant and transport gas. On the contrary, in the known processes for manufacturing glass containers, the PE-CVD, PI-CVD technique is applied in a distinct10 WO 20097019729 stage, at the end of and after the production process, and in particular in a different environment, using specifically dedicated systems and equipment. The new process, instead, as already explained, allows the MOCVD technique to be used in the annealing furnace, exploiting the thermal energy developed during the annealing stage. The following table reports the results of the chemical analysis of the solution extracted from a container in borosilicate glass through leaching, having the following chemical composition: 75 % SiOz, 11 % BrOs, 5 % AlzOs, 7 % Na,O, 2 % CaO + BaO, in the form of a 10 ml bottle for injectable solutions, whose inner surface is provided with a 150 nm layer of SiO2 applied according to said HTAP-MOCVD technique, tested on the base of the provisions of the European Pharmacopoeia 5" edition (2005), currently in force, regarding "Glass containers for pharmaceutical use — Hydrolytic resistance”. In the same table, said results are shown compared to the results obtained using an identical bottle for injectable solutions not provided with the layer of the invention on its inner surface. Each one of the values indicated is an average value obtained from the analyses carried out on 100 samples of glass containers Bottle with layer | Bottle without layer | ___ (ug/ml) 4,80 23, In the glass containers manufactured according to the present PCT/T2007/00071425 WO 20097019729 invention, the quantity of leached cations always remains below the detection limits. In particular, the layer of SiO2, chemically deposited, which forms a barrier between the phamaceutical or diagnostic solution and the glass matrix, is scarcely leachable and highly inert. The leachable quantity of Na cation, in fact, is below 0,01 ppm, while the leachable quantity of Si is below 0,30 ppm, when a 10 mi glass container with intemal layer obtained according to the present invention is tested according to the European Pharmacopoeia Sth edition (2005) for 1 hour at the temperature of 121 °C. The enclosed drawings schematically represent the new process and the equipment used, as examples without limitation Figure 1 shows the MOCVD deposition process inside a bottle (0) Figures 2 and 3 are two schematic views of a possible industrial application of the new process. As shown in Figure 1, the deposition (C) takes place at atmospheric pressure in a hot-wall CVD reactor (F) provided with a Pyrex tube ( The transport gas (V) is Nz of electronic grade (flow rate = 50 sccm) 1=50 mm) heated via a tubular electric furnace. passing through a bubbler (B) containing the precursor (P), that is, for example, said tri(dimethylamino)sitane The reactant gas (R1), that is O2 of electronic grade + vapor, is introduced in the main flow in the vicinity of the reaction area, with a flow rate of 150 sccm. The O2-H,0 mixture (R) is obtained by making the oxygen (R1) bubble in a 500 cc baloon (A) containing 250 cc of distilled water maintained at approximately 30°C. The reaction mixture (R) and the mixture made up of transport gas PCT/T2007/000714WO 2009/019729 PCTAT2007/000714 and precursor (VP) flowing out of said baloons (A, B) are injected (T), except for a waste portion (Rs, VPs), into the glass container (O), on whose internal surface the deposition (C) takes place. Figures 2 and 3 show the equipment where the reaction mixture (R) and the transport gas-precursor mixture (VP) are taken from the respective tanks (A1, B1) and injected inside the glass containers (O) by means of a series of injectors (T1, T). Therefore, with reference to the above description and the attached drawings, the following claims are expressed.WO 2009/019729 PCTAT2007/000714 CLAIMS 1. Process for manufacturing glass containers completely or partly treated with the chemical vapor deposition (CVD) technique, characterized in that it produces an inner layer of oxides of Si and/or 5 B and/or Ti and/or Zr and/or Ta and/or Al and/or mixtures of one or more of said elements deposited with the HTAP-MOCVD technique, and wherein said deposition is carried out during the annealing of the container itself, by supplying the annealing furnace with a suitable gas mixture of precursor, reactant and transport gas, and wherein 10 said layer actually makes up an inert barrier that prevents the extraction of the elements contained in the glass through the solutions present in the container. 2. Process according to claim 1, characterized in that it uses precursors whose general formula is: [R2N]nSiX4-n where R = alkyd 15 groups and X = H and alkyl groups in particular tri(dimethylamino)silane, [(CH3)2NJ3SiH, as precursor for the deposition of silicon dioxide, SiO2 3. Process according to claims 1, 2, characterized in that it uses N2 gas as transport gas, which is bubbled together with said 20 precursor. 4, Process according to claims 1, 2, characterized in that it uses 2 + H20 as reactant gas, wherein said gaseous oxygen is bubbled in at least one baloon containing H2O distilled at controlled temperature. 25 5, Glass container, characterized in that its surface is completely or partly treated with the HTAP-MOCVD technique, according to one or more of the preceding claims.WO 2009/019729 PCTAT2007/000714 6. Glass container according to claim 5, characterized in that the layer deposited on the whole or part of its surface contains Si02, and wherein the leachable quantity of Na cations is less than 0,01 ppm, when a 10 mi glass container is tested according to the European Pharmacopoeia 5'" edition (2005) for 1 hour at the temperature of 121°CSoe etyWO 20091019729 PCT/IT2007/000714 FIG.2PCT/IT2007/000714 WO 2009019729INTERNATIONAL SEARCH REPORT Internationa appllaton No PCT/1T2007/000714 “GLASSIECATION OF SUBJEOT MATT inv “coset77o0 Cosci7/02 —cosci7/245 —c03C17/30 According ntentional Patent Cassioton (IPC) orto bath national lassleton and PO ‘8. FIELDS SEARCHED ‘nn doaurantalon Searched (asian Sato ToVoned by casa SBOB] co3c acamtaon Search Oran rin Gocamantalon to ha anew tal sich Gocoman are Waided Th he os soared isco daa base Conaaiad during he tariaianal Soa aa ala BARD ah WhoTs PATA, Pow Ta wae) EPO-Internal, WPI Data (C. DOCUMENTS CONSIDERED TO BE RELEVANT (Categon” | Gaston of document, with inacaten, where appropri ofthe rtvanl passanee eleva cam No, x Us 5 997 948 A (DICK SAMI [FR] ET AL) 16 7 December 1999 (1999-12-07) abstract column 1, lines 11-17 40-44 claim 1 column 2, lines 33-35 column 4, lines 18-28 figure 3 x UP 06 076233 A (KANSAI NIPPON ELECTRIC) 1-6 18 March 1994 (1994-03-18) abstract X] Furter documents ara sled inthe continuation of Box . KX] seo patent tami annox 7 Spasial categorie of oad dosuorts “AY dociment dtning the general too the ast which sot ‘Conatere to be of parila Flovance Carter document but published on or tr th Ineraional “ng dae *U dcumor whic may throw doubts on pinyin) 0 is la aes ha pabscalon dio ose ‘San or oer spacial reason (as spectiot) 0" document refering tan os detosure use, exibon ot “Shr ans *P* document publ porta the niemstonl ing dat at Tarra ihe poy da aod a "7 ator document publshod tre ineratona ng date ‘pny doo an poh eseit the ape bl chide tnd he cae otheay Seng he “Xe docu of pala relvanoe ns caknad iyenton aot be conttred novel or Gaol bo Cotsared Ime an venvo stephen the securent token alone + suet of parle elvanoa; he caimad iverion ‘anno be cbnsired fo aie an oeiva_ sep wan the ‘foarte combined wih one ormoe Or sch doce Tee concinaon bog Soo 4a itd “8° document member athe same patent fmiy ‘Data ha ada complain oho Wioraonal arch 4 April 2008 Date of ating oa mlamaonal sone repr 16/04/2008 ‘Name ac raling adress ote ISAT European Palen ie, P.8, $818 Pitorisan 2 Mt" HV wre Tel (31-70) 340-2040, Tx 31 651 po n, Fae (1-70) 340-9016 ‘ahorod oar Mertins, FrédéricINTERNATIONAL SEARCH REPORT International appication No PcT/1T2007/000714 ‘E{Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Ccatogoy* (atone documan, wih nation, where appropri, of he retvant passages eevan to tim to x > >> LU 84 898 Al (INST NAT DU VERRE [BE]) 17 April 1985 (1985-04-17) page 3, lines 20-24, 34-36 page 4, lines 1-8 page 9, lines 7-16 claims 1,3,6,11,16,18 Us 6 537 626 B1 (SPALLEK MICHAEL [DE] ET AL) 25 March 2003 (2003-03-25) abstract claim 1 FR 2 697 014 A (SOUCHON NEUVESEL VERRERIES [FR]) 22 April 1994 (1994-04-22) abstract. page 5, lines 10-25 page 6, lines 17-22 clains 2,5 DE 296 09 958 U1 (SCHOTT GLASWERKE [DE]) 22 August 1996 (1996-08-22) page 1 claims 1-4 WALTHER MET AL: "PACKAGING OF SENSITIVE PARENTERAL DRUGS IN GLASS CONTAINERS WITH A QUARTZ-LIKE SURFACE" PHARMACEUTICAL TECHNOLOGY EUROPE - BIOPHARM, ADVANSTAR COMMUNICATIONS, CHESTER, , GB, vol. 8, no. 5, 1996, pages 22,24-27, xP000827860 ‘the whole document Us 3 182 839 A (EDWARD HOAG LEHNAN) 11 May 1965 (1965-05-11) the whole document US 5 431.707 A (DICK SAMI [FR] ET AL) 11 duly 1995 (1995-07-11) column 1, lines 54-68 1-6 5,6 1-4 5,6 1-4 5,6 5,6 5,6 1-4 1-6INTERNATIONAL SEARCH REPORT Intemational pplication No Information on patent family members PCT/I1T2007/000714 Patent document Publication Patent family Publication cited in search report ate member(s) ato us 5997948 A 07-12-1999 NONE oP 6076233, A 18-03-1994 NONE LU 84898 AL 17-04-1985 BE 900070 Al 03-01-1985 US. 6537626 Bl 25-03-2003 DE 19622550 AL 11-12-1997 EP 0811367 AZ 10-12-1997 ap 4037484 B2 23-01-2008 oP 10059371 A 03-03-1998 FR 2697014 A 22-04-1994 DE 29609958 Ul_—-22-08-1996 Us 3182839 A 11-05-1965 US 5431707 A 11-07-1995 DE 4327513 AL 03-03-1994 FR 2695118 AL 04-03-1994 oP 6191891 A 12-07-1994