(12) United States Patent
`Reibert et al.
`
`(10) Patent N0.:
`
`(45) Date of Patent:
`
`US 6,228,416 B1
`May 8, 2001
`
`US006228416B1
`
`(54) CELLULOSE ETHER HAVING ENHANCED
`GEL STRENGTH AND COMPOSITIONS
`CONTAINING IT
`
`(75)
`
`Inventors: Kenneth C. Reibert, Baton Rouge, LA
`(US); Jerry R. Conklin, Midland, MI
`(US)
`
`(73) Assignee: The Dow Chemical Company,
`Midland, MI (US)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`(21) Appl. No.: 09/283,506
`
`(22)
`
`Filed:
`
`Apr. 1, 1999
`
`Int. Cl.7 ................................................. .. A23L 1/0534
`(51)
`(52) U.S. Cl.
`............................ .. 426/573; 536/56; 536/84;
`106/163.01; 106/172.1
`(58) Field of Search ............................. .. 426/573; 536/56,
`536/84; 106/163.01, 172.1
`
`(56)
`
`References Cited
`PUBLICATIONS
`
`Whistler 1959 Industrial Gums, Polysaccharides and Their
`Derivatives Academic Press, New York p. 575-596.*
`Anon 1982 Methocel Food Gums in Pie and Pastry Fillings
`Form No. 192-878-482 Dow Chemical p. 1-15.*
`
`Anon 1982 Selecting Methocel Food Gums Dow Chemical
`p. 1-4.*
`Anon 1982 Methocel Food Gums in Non—Dairy Whipped
`Creams Dow Chemical p. 1-6.*
`Anon 1982 Methocel Food Gums in Fried Foods Dow
`
`Chemical p. 1-8.*
`Anon 1982 Methocel Food Gums in Salad Dressings and
`Sauces Dow Chemical p. 1-9.*
`Anon 1982 Methocel Sections 1-6 Dow Chemical Product
`Information form #192-882-682.*
`Anon 1982 Handbook on Methocel Cellulose Ether Prod-
`ucts Dow Chemical
`Product
`Information
`form
`#192-703-78.*
`
`* cited by examiner
`
`Primary Examiner—Carolyn Paden
`(74) Attorney, Agent, or Firm—Stanley K. Hill; J. Robert
`Dean, Jr.
`
`(57)
`
`ABSTRACT
`
`According to the present invention, there is a methylcellu-
`lose having a methoxy substitution of about 21 to about 42
`percent based upon the weight of the cellulose ether and
`elastic modulus (EM) of EM; 181.3><(v°'2711) wherein “V”
`is viscosity of a two percent solution of the cellulose ether
`at 20° C. Further described is a process for making the
`cellulose ether, a food composition containing it, and a
`pharmaceutical capsule containing it.
`
`25 Claims, 1 Drawing Sheet
`
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`

`
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`May 8, 2001
`
`US 6,228,416 B1
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`
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`

`1
`CELLULOSE ETHER HAVING ENHANCED
`GEL STRENGTH AND COMPOSITIONS
`CONTAINING IT
`
`2
`agent is contacted with the cellulose ether of second level of
`alkalization at about 65° C. to about 110° C. for 15 minutes
`or more.
`
`US 6,228,416 B1
`
`HELD OF THE iNVENTiON
`The present invention relates to a cellulose ether having
`enhaneed gel strength and a nioeess for inaking.
`
`5
`
`Further according to the present invention, there is a food
`composition comprising a foodstuff and the present cellulose
`ether‘
`.
`t
`t
`.
`Further according to the present 1hVeht10h,
`there is a
`pharmaceutical capsule comprising the present cellulose
`10 ether.
`
`DESCRIPTION OF THE DRAWING
`The FIGURE is a graphical representation depicting the
`elastic modulus of cellulose ethers of the present invention
`-
`and those of the prior art.
`
`BACKGROUND OF THE INVENTION
`Cellulose ethers have been employed as additives to food
`Corrlllpositlifnlas ahd plocessei to Progilde plhigsical properties
`Sue
`as t 1C emng’
`reeze/t aw Sta.
`1 Hy’
`11 nclty’ moisture
`retention and release, film formation, texture, consistency,
`.
`.
`.
`.
`.
`.
`shape retention, emulsification, binding, suspension, and 15
`DETAILED DESCRIPTION OF THE
`gelation.
`iNVENTiON
`Aphysical property important in some food compositions
`invention provides novel cellulose ethers
`The present
`is gei strehgth 0r eiastie rh0diihis~ This Pr0PertY reiates t0 the
`having elevated gel strength for a given viseositv grade and
`strength with which a cellulose ether binds or holds food
`Partieies t0gether~ Errerts t0 sighiheahtiy iherease gei 20 substitution type and level compared to that of conventional
`strehgth r0r e0hVehti0hai eeihiiese ethers heyehd ieVeis
`cellulose ethers. The cellulose ethers are useful in conven-
`0hserVed r0r giVeh Viseesity grades haVe heeh iargeiy iihsiie'
`tional cellulose ether applications, particularly in food com-
`eessriii~
`positions and pharmaceutical capsules.
`HaVihg a eeiiiiiese ether Whieh exhibits ehhaheed gei
`For purposes of the present invention, a cellulose ether is
`strehgth r0r giVeh Viseesity grades Weiiid ehahie r00d C0rh' 25 a cellulose ether With a methoxy substitution of about 21 to
`P0siti0hs With siiPeri0r hihdihga e0hsisteheY> ahd shaPe
`about 42 Weight percent based upon the Weight of the
`retehti0h t0 he deVei0Ped~ Ais0> Vise0sitY e0htrihiiti0h ahd
`cellulose ether. More preferred cellulose ethers have a
`cellulose ether concentrations could be reduced in food
`inetnoxy Substitution of about 21 to about 35 Weight percent
`e0rhP0siti0hs Whiie rhaihtaihihg desired gei hiheti0haiitY-
`and most preferred cellulose ethers have a methoxy substi-
`It would be desirable to have a cellulose ether which 30 tution of about 25 to about 35 Weight percent. Methoxy
`exhibits elevated gel strength for a given molecular weight
`substitution is determined according to ASTM D2363-72.
`or Viscosity grade. It Would also be desirable to have a
`Cellulose ethers having viscosities of up to about 1,000,
`pr0CeSS f0f making the Cell11l0Se ether.
`000 centipoise (cP) in a two percent aqueous solution at 20°
`35 C. can be prepared in the present
`invention. Preferred
`cellulose ethers may have viscosities of about 1 to about
`SUMMARY OF THE INVENTION
`600>000 CP (two Pereeht s0iiiti0h)- Mest Prererred eeiiiiiese
`According to the present invention, there is a methylcel-
`ethers rhay haVe Viseesities Or. ah0iit i t0 ab011t 1003000 CP
`lulose having a methoxy substitution of about 25 to about 42
`(two Pereeht s0iiiti0h)- Viseesities Or adiieeiis seiiitiehs are
`percent based upon the Weight of the cellulose ether and a
`visoositv (v)
`to elastic modulus (EM)
`relationship of 40 determined by Ubbelohde tube according to ASTM D1347-
`EM§181.3><(vO'2711). “ 2” means “greater than or equal to.”
`72 ahd D2363'79-
`Viscosity is for a 2 percent aqueous solution at 20° C. EM
`A useful embodiment of the present cellulose ether is a
`corresponds to gel strength.
`methylcellulose. The methylcellulose has a non-methoxy
`there is a
`invention,
`Further aeeoiding to the present
`substitution content or level of about 1 percent or less by
`process for making a cellulose ether. The process comprises 45 EVeig(ht ahd Plrlererahliy ahefit 0~f2 liliereehthelr ielsslhy Weiight
`the following: a) contacting a cellulose pulp with a first
`ase
`iiP0h t e t0ta Weig t 0 t e rhet Y ee ii 0se ah. is
`amount of aqueous alkaline hydroxide at reaction conditions
`rh0st Prererahiy siihstahtiaiiy rree. 0r.h0h.'rheth0XY siihstitii'
`sufficient to alkalize it to a first level of alkalization which
`tieh e0hteht~ N0h'rheth0XY siihstitiitieh ihehides but is het
`is about 20 percent or more of a total level of alkalization;
`iirhited to hYdr0XYethYi> hYdr0XYPr0PYi> ahd hydrexyhiityi
`b) contacting the cellulose pulp of first level of alkalization 50 siihstitiiti0h~
`with a first ainount of a methylating agent at reaction
`The present methylcellulose can exhibit an elastic modu-
`conditions sufficient to form a cellulose ether having a first
`1115 (EM) in a 1.5 Weight pereeht aqueous S0l1lti0h according
`level of methoxy substitution which is about 20 percent or
`to t>he
`follovgiznglz) EMd§181.3><(vf°'2:11); pre>ferably
`more of a total level of methoxy substitution; c) contacting
`EM=222~9>< V '
`; all
`H10St Pre era Y EM=490~6><
`the cellulose ether of first level of etherification with a 55 (V02406) Whereih “V” iS ViSCOSity Of a 2 Weight pereeht
`second amount of aqueous alkaline hydroxide at reaction
`aqueous S0l1lti0h at 20° C. EM C0freSp0hdS t0 gel strength.
`conditions sufficient
`to alkalize it
`to a second level of
`The above relationships are depicted graphically in the
`alkalization which is about 40 percent or more of the total
`FIGURE along With an analogous relationship for conven-
`leVel of alkalization; and d) continuously or incrementally
`tional methylcellulose. The relationship for conventional
`contacting the cellulose ether of second level of alkalization 60 methylcellulose iS repfeSeI1tati0I1al and deemed t0 be all
`with a second amount of a methylating agent over a period
`approximate average since actual viscosity to EM relation-
`of time at reaction conditions sufficient to form a cellulose
`ships for Various conventional methycellulose specimens
`ether of the second level of methoxy substitution which is
`Will Vary to some degree in a range above and below the
`about 40 percent or more of the total level of methoxy
`indicated approximate average. DEM in the FIGURE C01‘-
`substitution, the second amount of the methylating agent 65 feSP0hdS t0 EM-
`provides about 20 percent or more of the total level of
`EM is determined by measuring the storage modulus of a
`methoxy substitution; the second amount of the methylating
`1.5 Weight percent aqueous solution of the cellulose ether in
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`US 6,228,416 B1
`
`5
`
`4
`3
`invention is the
`An important aspect of the present
`a dynamic rheometer. Techniques for measuring elastic
`process by which the cellulose ether is made. This process
`modulus (storage modulus) are described in Kinetics of
`differs from that conventionally employed to make cellulose
`Thermal Gelation of Methylcellulose and Hydroxypropylm-
`ethers. In conventional processes, cellulose pulp is com-
`ethylcellulose in Aqueous Solutions, Carbohydrate
`pletely alkalized with sodium hydroxide and etherified with
`t
`.
`Polymers, volume 26, no. 3, pp. 195-203, which is incor-
`methyl chloride. In the present process, cellulose pulp. is
`pcrated herein by reference.
`partially alkalized and partially etherified with alkaline
`Cellulose ethers which can be made by the process or the
`ydroxide and methyl chloride in a first stage or step and
`.
`.
`.
`.
`.
`further alkalized and further etherified with additional alka-
`present Invention Include but are not limited to m°thy1C°1'
`10 line hydroxide and methyl chloride to the desired level of
`hulgse (b/hcl)’
`ht}:dlroiltli/il)r0pyI1{II]§l°\tlt1C-y1C°13110S°h (1H1l:°/llci’
`completion in a later stage or stages. Methyl chloride is
`y roxyet y met y Ce 11 0°°(
`)’ an met y et y Ce '
`continuously or incrementally introduced over a period of
`lulose (MEC)'
`time at certain reaction conditions in a second or later stage.
`Anotner iiseriii embodiment or tne Present oeiiiiiose etner
`The raw material used to make the present cellulose ether
`is a hydroxypropyhhothyloohuloso (HPMC)' HydroXybro'
`is cellulose. Cellulose pulp is typically obtained from wood
`pyl Substitutioh is preferably about 32 Weight porooht or loSS>
`more preferably about 1 to about 14 weight percent and most 15 pulp or cotton. The pulp is preferably provided in a powder
`preferably about 3 to about 12 weight percentbased upon the
`or chip form. Wood pulp is preferred.
`total Weight of the C°Hu10S° °th°r'
`.
`The alkalization and etherification of the cellulose pulp is
`Although hot bohhd by ahy thoory> tho ohhahood Physical
`carried out in a stepwise manner in stages. A “stage” refers
`ProPerties or tne Present oeiiiiiose etners rnay eorne rrorn 3 20 to a two-step reaction sequence in which an alkalization
`greater degree or “biooking” or Periodioity in rnetnoxy
`reaction and a methylation reaction take place. A stage
`substitution distribution in its polymeric structure than in the
`effectively advances or increases the level of rnethcxy
`structure of conventional cellulose ethers. The disclosed
`substitution of the cellulose pulp or a partially etherified
`Proooss ihay ihdhoo tho forihatioh of such biookihg-
`cellulose ether. Optionally, other types of etherification such
`The present Cell11lOSe ethers Can be SOl11ble in any Of 25 as hydroxypropyl substitution can be effected along with or
`water, polar organic solvents, and mixtures thereof depend-
`in addition to rriethoxy substitution,
`ing iiPon tne tYPe and degree or substitution or the oeiiiiiose
`The cellulose pulp is alkalized in two or more stages in
`etners~
`one or more reactors with an alkaline hydroxide, preferably
`In addition to enhanced gel strength, preferred cellulose
`sodium hydroxide. The pulp is partially alkalized in the first
`ethers may exhibit lower gelation temperatures than con- 30 stage and alkalized to a desired, total level of completion in
`ventional cellulose ethers of equivalent viscosity and sub-
`a second stage or a later stage. The pulp may be alkalized
`stitution. Lower gelation temperature is a desired and pre-
`with alkaline hydroxide by any means known in the art such
`ferred but non-essential feature of the present invention.
`as steeping in a bath or stirred tank containing aqueous
`Reduced gelation temperature is useful in food manufactur-
`hydroxide or spraying aqueous hydroxide directly on dry
`ing and processing. Food compositions can be gelled at 35 pulp. Reaction time varies according to hydroxide
`lower temperatures saving energy and processing time dur-
`concentration, temperature, and retention time. The aqueous
`ing heating/COOling cycles. Further, food compositions can
`hydroxide is preferably used at an alkaline hydroxide con-
`retain form at broader temperature ranges during processing.
`tent of about 30 to about 70 percent by weight based upon
`Gelation temperature is determined by heating a 1.5 percent
`the weight of the water. The temperature of alkylation
`by weight percent aqueous solution of the cellulose ether 40 preferably ranges from about 30° C. to about 110° C. and
`and observing the narrow temperature range at which gela-
`most preferably about 30° C.
`to about 90° C. Uniform
`tion takes place.
`swelling and alkali distribution in the pulp may be controlled
`Preferred cellulose ethers may also exhibit longer melt-
`by mixing and agitation. The rate Of additiOn Of aqueous
`back times than conventional cellulose ethers of equivalent
`alkaline hydroxide may be governed by the ability tO COOl
`viscosity and substitution. Meltback time generally refers to 45 the reaCtOf during the eXOthefIniC all<aliZatiOn reaCtiOn. The
`the length of time required for a gel of a cellulose ether to
`rate Of addition Of hydroxide iS not critical tO the present
`melt while cooling to an ambient temperature. Preferred
`invention. If desired, an organic solvent Such as dimethyl
`cellulose ether may even be stable (ho meltback) at ambient
`ether may be added tO the reactor as a diluent and a coolant.
`temperature (72° F. (22°
`Longer meltback time or
`If desired, the headspace of the reactor or reactors may be
`stability to meltback are desired and preferred but non-
`so evacuated or purged with an inert gas such as nitrogen to
`essential features of the present invention. Longer meltback
`control oxygen-catalyzed depolyrnerization of the cellulose
`time or stability to meltback at ambient temperature is useful
`ether pfOd1lCt.
`in food processing and manufacturing. Gelation can be
`The alkylated cellulose pulp is etherified (methylated) in
`maintained over a wider temperature range and longer and
`two or more stages in one or more reactors to form a
`better retention of texture during food processing and con- 55 cellulose ether. Reaction time for etherification will depend
`sumption are possible. Meltback time is determined accord-
`on concentration, pressure, temperature, and retention time.
`ing to the following: provide 15 grams of a 1.5 weight
`The primary etherifying agent isamethylating agent such as
`percent of an aqueous solution of the cellulose ether in a 20
`methyl chloride or dimethyl sulfate. Methyl chloride is
`milliliter beaker; heat the solution for 8 minutes in boiling
`preferred. The methylating agent may be added in a batch
`water—the solution will gel in the beaker; invert the beaker 60 load at one time or continuously or incrementally over a
`onto a flat surface in an ambient temperature environment;
`period of time in one or more stages but must be added
`allow the gel to cool and subsequently melt to form a puddle
`continuously or incrementally over a period of time in at
`on the surface. Meltback time is measured from the time
`least one stage after the first stage, preferably in the second
`cooling begins (removal from the boiling water) to when a
`stage. “Batch load addition” means addition substantially
`clear puddle forms. A gel is said to be stable to meltback if 65 without pause over a relatively short period of time. “Con-
`it cools to ambient temperature and resists melting for 8
`tinuous addition” means addition substantially without
`hours or more.
`pause over a longer period of time. “Incremental addition”
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`US 6,228,416 B1
`
`5
`means periodic addition of smaller, discrete amounts over a
`longer period of time. The alkaline hydroxide and the
`methylating agent may be added to the reactor at the same
`time but are preferably added sequentially with the alkaline
`hydroxide being added first and the methylating agent
`second.
`
`A two-stage process is the preferred process for making
`the present cellulose ether. In stage one, the aqueous alkaline
`hydroxide and the methylating agent are reacted in sequence
`with a cellulose pulp to form a partially etherified cellulose
`ether of a first level of methoxy substitution. Each of the
`alkaline hydroxide and the methylating agent may be added
`in stage one in a batch load at one time or continuously or
`incrementally over a period of time. The rate of addition is
`not critical. The reaction temperature in the first stage is
`preferably controlled so that generally uniform contact and
`reaction can occur between the alkaline hydroxide/
`methylating agent and the cellulose pulp. In the second
`stage, additional amounts of the aqueous alkaline hydroxide
`and the methylating agent are reacted with the partially
`etherified cellulose ether to form a cellulose ether with a
`
`second level or desired, total level of methoxy substitution.
`The alkaline hydroxide may be added in the second stage in
`a batch load at one time or continuously or incrementally
`over a period of time. The rate of addition of hydroxide in
`the second stage is not critical. The methylating agent must,
`however, be added continuously or incrementally over a
`period of time in the second stage to form the present
`cellulose ether. The methylating agent is added in the second
`stage at about 65° C.
`to about 120° C. (temperature of
`contents Within reactor) at 15 minutes or more; preferably at
`about 75° C. to about 100° C. at 20 minutes or more; and
`most preferably at about 80° C. to about 90° C. at 25 minutes
`
`10
`
`15
`
`20
`
`25
`
`30
`
`6
`to about 120° C. and more
`carry it out at about 65° C.
`preferably from about 80° C. to about 90° C. Temperature
`Within the reactor can be determined by means such as a
`thermocouple which protrudes into the contents (cellulose
`pulp/cellulose ether mass) of the reactor. In a preferred
`two-stage process, both stages are carried out in the same
`reactor. Preferably, about 20 to about 80 percent of the total
`methoxy substitution is carried out in the first stage and
`about 80 to about 20 percent in the second stage. More
`preferably, about 40 to about 60 percent of the total methoxy
`substitution is carried out in the first stage and about 60 to
`about 40 percent in the second stage. Some embodiments of
`two-stage processes are described in Table 1.
`Athree-stage process is also useful for making the present
`cellulose ether. The first stage is carried out in a manner
`similar to that of the first stage in the two-stage process
`described above. Either or both of the second and third
`
`stages are carried out in the same manner as the second stage
`in the two-stage process described above (the methylating
`agent is added continuously or incrementally over a period
`of time). In a preferred three-stage process, about 20 to about
`60 percent of the total methoxy substitution is carried out in
`each of the first and second stages and about 5 to about 30
`percent in the third stage. Some embodiments of three-stage
`processes are described in Table 1.
`It is also possible to have processes with four or more
`stages. The first stage of such a process would be carried out
`in the same manner as the first stage in the two-stage process
`described above. One or more of the subsequent stages
`would be carried out in the same manner as the second stage
`in the two-stage process described above (the methylating
`agent is added continuously or incrementally over a period
`of time).
`
`TABLE 1
`
`Some Useful Embodiments of the Process of the Present Invention
`
`Features
`
`partial alkalization in first stage; addition of alkaline hydroxide
`partial etherification in first stage; batch load addition of
`methylating agent
`partial etherification in first stage; continuous/incremental
`addition of methylating agent
`partial alkalization in second stage; addition of alkaline
`hydroxide
`partial etherification in second stage; continuous/incremental
`addition of methylating agent
`partial eterification in second stage; batch load or
`continuous/incremental addition of methylating agent
`partial alkalization in third stage; addition of alkaline hydroxide
`partial etherification in third stage; continuous/incremental
`addition of methylating agent
`partial etherification in third stage; batch load or
`continuous/incremental addition of methylating agent
`single reactor for all stages
`separate reactor for each stage
`
`Embodiments
`
`#1
`
`#2 #3
`
`#4
`
`#5
`
`#6
`
`#7 #8
`
`X X X X X X X X
`X X
`X X
`
`X X
`
`X X
`
`X X X X X X
`
`X X X X X X
`
`X X
`
`X X X X
`X X
`
`X X
`
`X
`
`X
`
`X
`
`X
`
`X
`
`X
`
`X
`
`X
`
`or more. Although the methylating agent can be added
`continuously or incrementally over any extended period of
`time in the second 15 stage, it is preferred for reasons of time
`economy to carry out the addition in about 120 minutes or
`less, more preferably in about 60 minutes or less, and most
`preferably in about 25 to about 45 minutes. After addition of
`the methylating agent in the second stage, etherification can
`be carried out at any temperature at which the reaction can
`proceed, but it is preferred for reason of time economy to
`
`60
`
`65
`
`Cellulose ethers such as hydroxypropylmethylcellulose,
`hydroxybutylmethylcellulose, methylethylcellulose and
`hydroxyethylmethylcellulose can be prepared by reacting
`the cellulose pulp or partially etherified cellulose ether with
`another etherifying agent in addition to the methylating
`agent (also an etherifying agent). Useful etherifying agents
`include ethyl chloride, ethylene oxide, propylene oxide, and
`butylene oxide. The other etherifying agent can be reacted in
`any stage before, during, or after reaction by the methylating
`
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`US 6,228,416 B1
`
`7
`8
`extruded fries; batters for fried foods, pancakes/waffles, and
`agent at process conditions sufficient to effect the desired
`cakes; pet foods; beverages; frozen desserts; cultured dairy
`reaction. The other etherifying agent may be added to the
`products such as ice cream, cottage cheese, yogurt, cheeses,
`reactor in a batch load or continuously/incrementally over a
`and sour creams; cake icing and glazes; whipped topping;
`period of time. Preferably,
`the other etherifying agent is
`leavened and unleavened baked goods; and the like. In
`.
`.
`.
`.
`.
`reacted in the first stage. Preferably, the other etherifying 5
`forming feed eempesitiene. the eeiiuiese ether is typically
`agent is reacted before or along with the methylating agent.
`admixed with foodstuffs during the process and formation of
`.
`.
`.
`.
`.
`.
`The methylating agent and any other etherifying agent
`the compositions. The foodstuffs may be in any known form
`.
`.
`.
`.
`.
`.
`.
`.
`may be added to a reactor in a liquid or vapor form. Liquid
`such as particle form or unitary form. Excellent teachings to
`.
`.
`.
`.
`.
`.
`.
`.
`form is highly preferred. The reactor is preferably main-
`the preparation of food compositions with cellulose ether
`.
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`d .
`d
`th
`11
`1
`th
`th
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`tained at pressures such that the agents remain predomi- 10
`e
`oun
`er ce u ose e ers are
`in
`o owing
`o
`an
`nanoy in liquid phase.
`METHOCEL® (trademark of The Dow Chemical
`Af
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`Company) product publications: METHOCEL Premium
`to
`ter et en Canon’
`t 6. Ce 11 ose ct er
`15 was 6
`Food Gums Form NOS 192_1037_87 192_1047_87 192_
`remove salt and other reaction by-products. Any solvent in
`1046_87
`1§2_1051_87 '192_1050_87 ’ 192_1049_87’ 192_
`which salt is soluble may be employed, but water is pre-
`ferred. The cellulose ether may be washed in the reactor, but 15 105387’ 192_982_87 i92_979_87 19’2_985_87 192:1054_
`is preferably washed in a separate washer located down-
`87
`192’_1048_87
`19’2_987_87
`1’92_986_87
`i92_989_87
`stream of the reactor. Before or after washing, the cellulose
`19’2_988_87
`192:984_87 192:983_87 192398187 192:
`ether may be stripped by expesure te steam te reduee
`991-87 192,-980-87 192-990-87 and 1,92-1052-87 (all pub-
`residuai ergariie eenterit
`lished in 1987) selecting METIiVOCEL Food Gums Form
`The cellulose ether is dried to a reduced moisture and 20 No.192_855_1281R (published in 1981); METHOCEI: Food
`volatile content of preferably about 0.5 to about 10.0 weight
`Gums In Non_Ddl',,y Whipped Topping) Form No. 192-877-
`percent water and more preferably about 0.8 to about 5.0
`482 (published in 1982); METHOCEL Food Gums In Fried
`weight percent water and volatiles based upon the weight of
`Foods) Form NOS. 192_875_482 and 192_881_482 (an pub_
`cellulose ether. The reduced moisture and volatiles content
`fished in 1982); METHOCEL Food Gums In Salad D,,eSS_
`enables the cellulose ether to be milled into particulate form. 25 logs and Sauces) Form NOS. 192_876_482’ 192_880_482’ and
`The cellulose ether is preferably dried at a temperature of
`192_905_1282 (all published in 1982); and METHOCEL
`from about 40° C. to about 80° C. Useful dryers include tray
`Food Gums 1” Bakery products) Form NOS. 192_874_482
`dryers, fluid bed dryers, flash dryers, agitation dryers, and
`and 192-878-482 (all published in 1982). The teachings of
`tube dryerS~
`30 all the above publications are incorporated herein by refer-
`The cellulose ether is milled to particulates of desired
`erroe.
`siZe- if desired, drying and miiiing may be Carried Oiit
`Cellulose ethers particularly useful in food compositions
`Simiiitane0iiSiy~ Miiiing may be aee0mPiiShed by any means
`are methylcellulose and hydroxypropylmethylcellulose.
`kn0Wn in the art sneh as a bah miii, an impact PiiiVeriZer,
`Cellulose ethers are typically used in food compositions at
`kniie grinder, and air'SWePt imPaet miii-
`35 levels of about 0.01 to about 5 percent based upon the total
`The present invention distinguishes the prior art. U.S. Pat.
`weight of the food composition.
`N0s~ 4,456,751; 4,477,657; and 4,661,589 reiate tW0'Stage
`Cellulose ethers are useful in other applications such as
`Preeesses for making hydrekyaikyieeiiiiieses Wherein an
`building products, industrial products, agricultural products,
`aikyiene Oxide is added eentineiisiy in the first Stage and
`personal care products, household products, and pharma-
`another etherifying agent S1lCll as
`chloride iS added 40 Ceutical prgducts. Useful pharmaceutical applicatigns
`eentiniieiisiy in the Seeend Stage~ The Present Pr0eeSS dis‘
`include as capsules, encapsulants, tablet coatings, and as an
`tingiiishes these Processes in Part in that a methyiating agent
`excipients for medicaments and drugs. Useful excipient
`Such as methyi ehieride is added in b0th the first and SeC0nd
`functions include as sustained-release and timed-release
`StageS~ U-S~ Pat N0- 4,661,589 ais0 reiates a tW0 stage
`tablets. Useful building applications include drywall tape-
`process wherein propylene oxide and a diluent Of partial 45 jgint Cgmpgunds, mgrtars, grguts, Cement plasters, Spray
`methyi ehieride eentent are added in VaP0r Phase in a first
`plasters, cement stucco, adhesives, pastes, and wall/ceiling
`stage and methyi ehieride is added eentiniieiisiy in the
`texturizers. Useful industrial applications include binders
`Seeend Stage- The Present Preeess distingnishes that Preeess
`and processing aids for tape casting, extrusion forming, and
`in Part in that the quantity 0i methyiating agent added in the
`injection molding and ceramics. Useful agricultural appli-
`hrst Stage is snfheient t0 Pr0Vide a ieVei Oi meth0Xy snb' 50 cations include spray adherents and suspending/dispersing
`Stitiitien Which is abeiit 20 Pereent 0r mere Or a desired, t0tai
`aids for pesticide, herbicide, and fertilizer powders. Useful
`ieVei Oi meth0Xy SiibStitiiti0n~ The Present Pr0eeSS Prediiees
`personal care and household products include shampoos,
`cellulose ethers having significantly greater gel strength than
`iotions, Creams, and C16 aning products.
`Prier art eeiiiiiese ethers Oi ediiiVaient Viseesity grade and
`The present cellulose ethers are particularly useful in
`Substitution German
`55 compositions for pharmaceutical capsules. Capsules formed
`APPiieati0n 1,060,374 reiates a Preeess fer making Water‘
`from the present cellulose ethers may exhibit substantially
`insoluble methylcellulose wherein methyl chloride is added
`less distortion after drying than capsules formed from con-
`ih tW0 stages- The Present
`ihVehti0h distihgilishes that
`ventional cellulose ethers. Particularly useful cellulose
`pf0CeSS in part
`in that a methylating agent
`iS added
`ethers are methylcellulose and hydroxypropylmethylcellu-
`continuously/incrementally in the SeCOI1d Stage and the 60 lose of low molecular weight, i.e. about 3 to about 100 cP
`product cellulose ether is water soluble or swellable.
`and preferably about 3 to about 15 CP in a two percent
`The present cellulose ether is useful in a variety of food
`aqueous solution. Low molecular weight cellulose ethers
`compositions. Examples of food compositions include
`can be prepared directly from the process described above or
`vegetable, meat, and soy patties;
`reformed seafood;
`can be prepared from high molecular cellulose ethers via
`reformed cheese sticks; cream soups; gravies and sauces;
`65 acid-catalyzed depolymerization. Useful acids include anhy-
`salad dressing; mayonnaise; onion rings; jams, jellies, and
`drous hydrogen chloride and hydrochloric acid. Following
`syrups; pie filling; potato products such as french fries and
`depolymerization to the desired degree, the acid is neutral-
`
`Mylan v. Qualicaps, |PR2017—OO203
`QUALICAPS EX. 2024 — 6/10
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2024 - 6/10
`
`

`

`US 6,228,416 B1
`
`5
`
`10
`9
`organic by-products. The wet cellulose ether was then
`ized and the depolymerization stopped by contact with a
`transferred to a dryer where moisture and volatiles content
`base such as sodium bicarbonate. Useful teachings relating
`was reduced to 1 to 4 weight percent based upon the weight
`to making low molecular weight cellulose ethers are seen in
`U.S. Ser. No. 09/203,324, filed Dec. 1, 1998, which is
`of the cellulose ether. The cellulose ether was then ground to
`a particle size of about 40 mesh (420 micrometers).
`incorporated herein by reference.
`The cellulose ether product was analyzed and found to
`Cellulose ether capsules are typically manufactured by
`contain 31.8 percent methoxy substitution (a methoxy
`dipping hot pins in a cold, aqueous cellulose ether coating
`degree of substitution of 1.96). It exhibited a viscosity of
`solution or by dipping cold pins in a hot, aqueous cellulose
`17,000 centipoise (cP) in a 2 percent by weight aqueous
`ether coating solution. The solutions gel on the pins and
`water evaporates during a drying step to form thin film 10 solution by weight, a gelation temperature (Tgel) of 105°
`layers of dried cellulose ether around the pins. The thin films
`F.—108° F. (40.6° C.—42.2° C.), and a elastic modulus (EM)
`take the form of caps and bodies, which are removed from
`of 5445 Pascals for a 1.5 percent by weight aqueous
`the pins and mated to form capsules. Processes for making
`solution, and a meltback time of 35 minutes. EM corre-
`capsules are seen in U.S. Pat. Nos. 3,617,588; 4,001,211;
`sponds to gel strength. These physical properties are more
`4,917,885; and 5,756,036, which are incorpo