United States Patent
`
`[19]
`
`l|||||llllllllllllllll||||l||||||lll|l|l||||lll|||||lllllllllllllllllllllll
`U3005393491A
`[11] Patent Number:
`
`5,393,491
`
`Dassanayake et a].
`
`[45] Date of Patent:
`
`Feb. 28, 1995
`
`[54] USE OF AMIDOAMINES 1N OPHTHAme
`COMPOSITIONS
`
`................... 252/105
`4,738,790 4/1988 Miyajima et al.
`5,215,976
`6/1993 Fost et a1.
`........................... 514/114
`
`[75]
`
`Inventors: Nissanke L. Dassanayake, Arlington;
`Ronald L. Schlitzer, Forth Worth;
`Joonsup Parka Arlington, all of Tex.
`[73] Assignee: Alcon Laboratories, Inc., Fort
`Worth, Tex.
`
`OTHER PUBLICATIONS
`' D‘ -
`k,T.M.,tal.,“FttA'd
`M
`uzycz o
`e
`a y mi oannne
`enva
`tives: N,N—Dimethy1—N—(3~alky1amidopropyl)amines
`and Their Salts,” Journal of the American Oil Chemists’
`Society, vol. 45, No. 11, pp. 720—725 (1968).
`
`[21] App]. No.: 125,629
`.
`_
`Sep. 22’ 1993
`[22] Filed"
`[51]
`Int. Cl.6 ........................ A01N 33/02; A61L 2/18
`[52] US. Cl. ...................................... 422/28; 514/840;
`424/7504; 252/546
`[58] Field of Search .......................... 422/28; 252/546;
`514/839, 840; 424/78.04
`References Cited
`U.S. PATENT DOCUMENTS
`
`[56]
`
`Primary Examiner—Robert J. Warden
`Assistant Examiner—E. Leigh Dawson
`Attorney, Agent, or Firm—James A. Arno; Gregg C.
`Brown
`
`ABSTRACT
`[57]
`Certain amidoamines, the use of same for disinfecting
`and cleaning contact lenses and preserving ophthalmic
`products, and associated ophthalmic compositions are
`described.
`
`4,407,791 10/1983 Stark ..................................... 424/80
`
`18 Claims, No Drawings
`
`Argentum Pharm. LLC V. Alcon Research, Ltd.
`Case IPR2017-01053
`
`ALCON 203 7
`
`

`

`1
`
`5,393,491
`
`2
`As a result, the compounds also help to clean contact
`lenses by facilitating the removal of deposits from the
`lenses.
`The amidoamines of the present invention retain their
`antimicrobial activity in the presence of Na+, Ca++,
`Cl- and other inorganic ions produced by the dissocia
`tion of alkaline and alkaline earth metal salts (e.g., so
`dium chloride and calcium chloride), and are compati
`ble with polymers and surfactants frequently used in
`ophthalmic products, such as polyvinylpyrrolidone,
`and polyoxyethylene/polyoxypropylene copolymers of
`ethylene diamines. These properties represent signi?
`cant advantages, relative to many of the antimicrobial
`agents previously used in the ophthalmic ?eld.
`
`DESCRIPTION OF PREFERRED
`EMBODIMENTS
`The compounds used in the present invention com
`prise one or more compounds of the following formula,
`or pharmaceutically acceptable salts thereof (e.g., hy
`drohalide salts):
`
`H
`R1—C-'NH-(CH2)F'N—(RZ)2
`
`(I)
`
`wherein:
`R1 is C6-C13 saturated or unsaturated alkyl, alkylaryl,
`or alkoxyaryl;
`n is 2 to 16; and
`R2 is C1-C3 saturated or unsaturated alkyl or alkanol.
`The compounds wherein R2 is methyl or ethyl and n is
`2 to 4 are particularly preferred, as are the following
`compounds:
`
`Compound No.
`
`1
`2
`3
`4
`5
`6
`
`R1
`
`C17
`C13
`C13
`C13
`C11
`C11
`
`n
`
`3
`2
`2
`3
`3
`3
`
`R2
`
`CH3
`CH3
`021-15
`CH3
`CH3
`C2H5
`
`The most preferred compound is Compound No. 5,
`which is known as N,N-Dimethyl-N’-dodecanoyl-1,3
`propylenediamine.
`The compounds of the present invention can be syn
`thesized in accordance with the following reaction
`scheme:
`
`USE OF AMIDOAMINES IN OPHTHALMIC
`COMPOSITIONS
`
`5
`
`BACKGROUND OF THE INVENTION
`The present invention relates to the ?eld of ophthal
`mology. More particularly, the invention is directed to
`compositions and methods for disinfecting contact
`lenses, and to the chemical preservation of various types
`of ophthalmic products. Contact lenses are exposed to a
`broad spectrum of microbes during normal wear and
`become soiled relatively quickly. Routine cleaning and
`disinfecting of the lenses are therefore required. Al
`though the frequency of cleaning and disinfecting may
`vary somewhat among different types of lenses and lens
`care regimens, daily cleaning and disinfecting is nor
`mally required. Failure to clean and disinfect the lens
`properly can lead to a multitude of problems ranging
`from mere discomfort when the lenses are being worn
`20
`to serious ocular infections. Ocular infections caused by
`particularly virulent microbes, such as Pseudomonas
`aeruginosa, can lead to loss of the infected eye(s) if left
`untreated or if allowed to reach an advanced stage
`before treatment is initiated. It is therefore extremely
`important that patients disinfect their contact lenses in
`accordance with the regimen prescribed by their op
`tometrist or ophthalmologist.
`Unfortunately, patients frequently fail to follow the
`prescribed regimens. Many patients ?nd regimens to be
`di?icult to understand and/or complicated, and as a
`result do not comply with one or more aspects of the
`regimen. Other patients may have a negative experience
`with the regimen, such as ocular discomfort attributable
`to the disinfecting agent, and as a result do not routinely
`disinfect their lenses or otherwise stray from the pre
`scribed regimen. In either case, the risk of ocular infec
`tions is exacerbated.
`Despite the availability of various types of contact
`lens disinfecting systems, such as heat, hydrogen perox
`ide, and other chemical agents, there continues to be a
`need for improved systems which: 1) are simple to use,
`2) have potent antimicrobial activity, and 3) are non
`toxic (i.e., do not cause ocular irritation as the result of
`binding to the lens material). Moreover, the chemical
`agents utilized in the currently marketed contact lens
`disinfection systems generally have limited antifungal
`activity. Also, many of the chemical agents currently
`utilized may interact with contact lens materials and/ or
`cause irritation in some individuals. There is, therefore,
`a particular need in the ?elds of contact lens disinfection
`and ophthalmic composition preservation for safe and
`effective chemical agents having better antifungal activ
`ity. The present invention is directed to satisfaction of
`the above-cited needs.
`
`25
`
`30
`
`35
`
`45
`
`SUMMARY OF THE INVENTION
`The present invention is directed to methods of using
`certain amidoamines to disinfect contact lenses and to
`preserve ophthalmic compositions. The invention is
`also directed to contact lens disinfecting compositions
`which contain one or more of the subject compounds,
`and to various types of ophthalmic compositions (e.g.,
`pharmaceuticals, arti?cial tears and comfort drops)
`which contain the compounds for purposes of preserv
`ing the compositions against microbial contamination.
`In addition to having antimicrobial activity, including
`both antibacterial and antifungal activity, the com
`pounds of the present invention are also surface active.
`
`55
`
`65
`
`The following article may be referred to for further
`details concerning the synthesis of the amidoamines of
`formula (I): Muzyczko, et al., “Fatty Amidoamine De
`rivatives:
`N,N-Dimethyl-N-(3-alkylamidopropyl)a
`mines and Their Salts”, Journal of the American Oil
`Chemists’ Society, volume 45, number ll, pages 720-725
`(1968). The entire contents of the above-cited article are
`hereby incorporated in the present speci?cation by
`reference. The above-cited article does not describe the
`use of compounds of formula (I) as disinfectants or
`preservatives in ophthalmic products, particularly
`products used in the care of contact lenses.
`
`

`

`25
`
`5,393,491
`3
`4
`The compounds of formula (I) can be used individu
`compatibility of the compounds of formula (I) is also a
`signi?cant advantage with respect to the use of these
`ally, in combination with one or more other compounds
`compounds in the contact lens disinfecting composi~
`of formula (I), or in combination with other disinfec
`tions of the present invention.
`tants or preservatives. The compounds may, for exam
`ple, be used in combination with the polymeric quater
`The above-described compositions may be used to
`nary ammonium compounds described in U.S. Pat. No.
`disinfect contact lenses in accordance with processes
`4,407,791; the entire contents of that patent are hereby
`known to those skilled in the art. More speci?cally, the
`incorporated in the present speci?cation by reference.
`lenses will ?rst be removed from the eyes of the pa
`As described in the ’791 patent, those polymeric quater
`tients, and then will be immersed in the compositions
`nary ammonium compounds are useful in disinfecting
`for a time suf?cient to disinfect the lenses. This immer
`contact lenses and preserving ophthalmic compositions.
`sion will typically be accomplished by means of soaking
`The amount of each compound used will depend on
`the lenses in a solution overnight (i.e., approximately six
`the purpose of the use, e.g., disinfection of contact
`to eight hours). The lenses will then be rinsed and
`lenses or preservation of ophthalmic products, and the
`placed in the eye. Prior to immersion in the disinfecting
`compositions, the lenses will preferably also be cleaned
`absence or inclusion of other antimicrobial agents. The
`concentrations determined to be necessary for the
`and rinsed.
`The compounds of formula (I) also have surface ac
`above-stated purposes can be functionally described as
`“an amount effective to disinfect” and “an amount ef
`tive properties. As a result of these properties, the com
`fective to preserve” or variations thereof. The concen
`pounds are also useful in cleaning contact lenses. More
`speci?cally, the surfactant properties of the compounds
`trations used for disinfection will generally be in the
`facilitate the removal of deposits typically accumulated
`range of from about 0.0001 to about 0.1 percent by
`weight based on the total weight of the composition
`on contact lenses when worn by human patients. These
`(“wt %”). The concentrations used for preservation
`deposits vary from patient to patient, but will typically
`include proteins, lipids, polysaccharides and mixtures
`will generally be in the range of from about 0.00001 to
`about 0.01 wt. %.
`thereof, as well as various other soils which may accu
`The compounds of formula (I) may be included in
`mulate on the lenses during normal wear and handling.
`various types of ophthalmic compositions as preserva
`The compounds will exhibit some cleaning effect even
`at the relatively low concentrations required for pur
`tives, so as to prevent microbial contamination of the
`compositions. The types of compositions which may be
`poses of preserving ophthalmic compositions or disin
`preserved by the compounds of formula (I) include:
`fecting contact lenses. This cleaning effect is therefore
`ophthalmic pharmaceutical compositions, such as topi
`useful as a supplement to the effect of other cleaning
`cal compositions used in the treatment of glaucoma,
`agents which may be contained in the compositions,
`infections, allergies or in?ammation; compositions for
`such as anionic or nonionic surfactants. Moreover,
`treating contact lenses, such as cleaning products and
`when used at a concentration of 0.01 wt. % or higher,
`products for enhancing the ocular comfort of patients
`the compounds exhibit a more pronounced cleaning
`wearing contact lenses; and various other types of com
`effect. The manner in which the cleaning effect of the
`positions, such as ocular lubricating products, arti?cial
`compounds of formula (I) is utilized will depend on the
`type of contact lens being treated, the severity and type
`tears, astringents, and so on. The compositions may be
`aqueous or nonaqueous, but will generally be aqueous.
`of the deposits on the lenses, and the overall treatment
`As will be appreciated by those skilled in the art, the
`regimen used by the patient. The selection of other
`compositions may contain a wide variety of ingredients,
`components for inclusion in the contact lens cleaning
`such as tonicity agents (e.g., sodium chloride or manni
`compositions of the present invention will also depend
`tol), surfactants (e.g., polyvinyl pyrrolidone and po
`on these factors. The cleaning compositions will gener
`lyoxyethylene/polyoxypropylene copolymers), viscos
`ally contain one or more of the compounds of formula
`ity adjusting agents (e.g., hydroxypropyl methyl cellu
`(I) in an amount of at least 0.01 wt. %, and preferably
`lose and other cellulose derivatives) and buffering
`from about 0.01 to 1.0 wt. %.
`agents (e.g., borates, citrates, phosphates and carbon
`The above-described compositions may be used to
`ates). The present invention is not limited with respect
`clean contact lenses in accordance with known pro
`to the types of ophthalmic compositions in which the
`cesses. For example, the lenses, after ?rst being re
`compounds of formula (I) may be contained as preser
`moved from the eye and preferably also rinsed, may be
`vatives. In fact, as already noted above, the compatibil
`lightly rubbed with a small amount of the compositions
`ity of the compounds of formula (I) with other ingredi
`between the ?ngers, or may be immersed in a somewhat
`ents of ophthalmic compositions, such as inorganic ions,
`larger volume of the compositions and then allowed to
`polymers and surfactants, is a distinct advantage of the
`soak. The lenses are then rinsed and disinfected before
`present invention, relative to antimicrobial agents previ
`being replaced in the eyes of the patients.
`ously utilized in the ophthalmic field.
`All of the above-described compositions will be for
`As with the ophthalmic compositions of the present
`mulated so as to be compatible with the eye and/or
`contact lenses to be treated with the compositions. As
`invention which contain one or more compounds of
`formula (I) as preservatives, the form of the composi
`will be appreciated by those skilled in the art, the oph
`thalmic compositions intended for direct application to
`tions of the present invention containing one or more of
`60
`the compounds for purposes of disinfecting contact
`the eye will be formulated so as to have a pH and tonic
`lenses is not limited. The contact lens disinfecting com
`ity which are compatible with the eye. This will nor
`positions of the present invention will preferably be
`mally require a buffer to maintain the pH of the compo
`formulated as aqueous solutions, but may also be formu
`sition at or near physiologic pH (i.e., 7.4) and may re
`quire a tonicity agent to bring the osmolality of the
`lated as nonaqueous solutions, as well as suspensions,
`gels, and so on. The compositions may contain a variety
`composition to a level at or near 300-320 milliosmoles.
`of tonicity agents, surfactants, viscosity adjusting agents
`The formulation of compositions for disinfecting and
`and buffering agents, as described above. The chemical
`/ or cleaning contact lenses will involve similar consid
`
`40
`
`45
`
`65
`
`

`

`5,393,491
`
`‘
`
`5
`erations, as well as considerations relating to the physi
`cal effect of the compositions on contact lens materials
`and the potential for binding or absorption of the com
`ponents of the composition by the lens.
`The compositions and methods of the present inven
`tion, may be used in conjunction with various types of
`contact lenses, including both lenses generally classi?ed
`as “hard” and lenses generally classi?ed as “soft”.
`The following examples are presented to further illus
`trate methods of synthesizing the amidoamies utilized in
`the present invention:
`EXAMPLE 1
`N,N-Dimethyl-N'-Dodecanoyl-l,3-Propylenediamine
`(Compound No. 5)
`A 500 ml RB ?ask containing a solution of lauroyl
`chloride (19.38 g., 89 mM) in dry chloroform (200 ml)
`was cooled to 0° C. on an ice bath. A solution of N,N
`dimethyl-l,3-propanediamine (10.40 g., 51 mM) and
`triethylamine (9.40 g., 93 mM) in dry chloroform (25ml)
`was added dropwise to the cold solution through an
`addition funnel, then allowed to warm to room temper
`ature and stirred for 2 hours. The chloroform was re
`moved under reduced pressure and the residue redis
`solved in an ethanol/water mixture (1:1) and neutral
`ized with sodium bicarbonate, followed by extraction
`with chloroform (4X50 ml). The combined extracts
`were dried (MgSO4), concentrated, and the residue
`distilled under reduced pressure (bp 171° C., 10p.) to
`give 23.92 g. (68%) of the subject compound as an
`amber solid.
`PMR (200 MHz, CDC13): 83.33 (q, 2 H, NH—CH2),
`3.37 (t, 2H, CH2N(CH3)2), 2.23 (s, 6 H,N(CH3)2), 2.15
`(t, 2 H, CHZCO), 1.62 (m, 4 H, CHZCHZCO,
`CH2CH2N(CH3)2), 1.26 (s, 16 H, —-CH2—), 0.88 (t, 3
`H). Analysis: Calculated for C17H36N2O: C, 71.77; H,
`12.75; N, 9.85. Found: C, 72.06; H, 12.76; N, 9.94. IR
`(neat): 3280, 2910, 2840, 2800, 2750, 1460, 1370, 1260,
`1125, 1035 cm-1.
`
`5
`
`10
`
`20
`
`25
`
`45
`
`50
`
`EXAMPLE 2
`N, N-Dimethyl~N’-Tetradecanoyl~ 1,3-Propylenedia
`mine (Compound No. 4)
`2.0 g. (0.0196 moles) of 3-dimethylaminopropylamine
`in 40 ml chloroform was added dropwise to an ice cold
`chloroform solution (50 ml) of myristoyl chloride (4.17
`g., 0.0169 moles). After addition, the ice bath was re
`moved and the solution was stirred for 2 hours. A 25 ml
`aqueous sodium bicarbonate solution was added and
`stirred for 30 minutes. The organic layer was then
`washed with 30 ml aqueous sodium bicarbonate/ sodium
`chloride solution and dried with magnesium sulfate.
`The solution was concentrated in vacuo and the amide
`was recrystallized in ethyl acetate to yield 3.29 g.
`(0.0105 moles, 62.3%) of the subject compound.
`PMR (200 MHz, CDCL3): 86.9 (s, 1H, NH), 3.3 (q,
`3H, NHCHZ), 2.4 (t, 2H, NCH;), 2.22 (s, 6H, NCH3),
`2.15 (t, 2H, COCHZ), 1.7-1.5 (m, 4H, COCHZCHZ and
`NHCHZCHZ), 1.25 (s, 20H, COCH1CH2(CH2)10), 0.88
`(t, 3H, CH3). Elemental Analysis: Calculated for
`C19H40N2O (312.52): C, 73.02; H, 12.90; N, 8.96. Found:
`C, 72.96; H, 12.92; N, 8.93
`
`6
`EXAMPLE 3
`N,N-Diethyl-N’-Tetradecanoyl-1,2-Ethylenediamine
`(Compound No. 3)
`8.35 g. (0.072 moles) of diethylethylenediamine in 40
`ml chloroform was added dropwise to an ice cold chlo
`roform solution (60 ml) of myristoyl chloride (15.84 g.,
`0.064 moles). After addition, the ice bath was removed
`and the solution stirred for 6 hours. The reaction mix
`ture was then stirred with aqueous sodium bicarbonate
`for 10 minutes and the organic layer was washed with
`an aqueous sodium bicarbonate/sodium chloride solu
`tion. The organic layer was then dried over magnesium
`sulfate and concentrated in vacuo leaving a white solid.
`The amide was recrystallized in ethyl acetate, ?ltered
`and dried to yield 16.58 g. (0.051 moles, 79.1%) of the
`subject compound.
`PMR (200 MHz, CDCl3): 86.2 (s, 1H, NH), 3.3 (q,
`2H, NHCHZ), 2.6—2.5 (m, 6H, NCH;), 2.2 (t, 2H,
`COCHg), 1.6 (m, 2H, COCHZCHZ), 1.25 (s, 20H,
`COCHZCHZ (CH2)1Q), 1.03 (t, 6H, NCH2CH2CH3), 0.88
`(t, 3H, CH3). Elemental Analysis: Calculated for
`C20H42N2O (326.54): C, 73.56; H, 12.96; N, 8.58 Found:
`C, 73.44; H, 12.97; N, 8.56
`EXAMPLE 4
`N,N-Diethly-N’-Dodecanoyl-1,3-Propylenediamine
`(Compound No. 6)
`A 500 ml RB ?ask containing a solution of lauroyl
`chloride (19.03 g., 87 mM) in dry chloroform (200 ml)
`was cooled to 0° C. on an ice bath. A solution of N,
`N-diethly-l,3-propanediamine (15.00 g., 115 mM) in dry
`chloroform (25 ml) was added dropwise to the cold
`solution then allowed to warm to room temperature and
`stirred for 2 hours. The chloroform was removed under
`reduced pressure and the residue redissolved in an
`ethanol/water mixture (1:1) and neutralized with so
`dium bicarbonate, followed by extraction with chloro
`form (4X50 ml). The combined extracts were dried
`(MgSO4), concentrated, and the residue distilled under
`reduced pressure (bp 176° C., 201.1.) to give 21.47 g.
`(79%) of the subject compound as an amber oil.
`PMR (200 MHz. CDC13): 83.33 (q, 2 H,NH—CH2),
`2.52 (m, 6 H, CH2N(CH2CH3)2), 2.15 (t, CHZCO), 1.63
`(m, 4 H, CH2CH2CO, CH2CH2N(CH2CH3)2), 1.25 (s,
`16 H, —CH2—-), 1.04 (t, 6 H, N(CH2CH3), 0.88 (t, 3 H,
`—CH3). IR (neat): 3280, 3080, 2910, 2840, 2800, 2750,
`1640, 1550, 1460, 1370, 1280, 1100, 1060 cm—1. MS (Cl):
`m/ e 313 (MH+)
`The following examples are presented to further illus
`trate ophthalmic compositions which may contain one
`or more of the compounds of formula (I):
`
`EXAMPLE 5
`The following formulation might serve as a vehicle
`for an ophthalmic drug. The formulation would contain
`one or more compounds of formula (I) as a preserva
`tive.
`
`Ingredient
`Sodium Chloride
`Mannitol
`HEPES
`NaOfUHCl
`Puri?ed water
`
`Amount (wt. %)
`0.5%
`2.5%
`0.119%
`pH 7.0
`QS 100
`
`

`

`7
`EXAMPLE 6
`The following formulation may be utilized as a
`contact lens disinfecting solution. The formulation
`would contain one or more compounds of formula (I) as
`a disinfectant.
`
`Ingredient
`Mannitol
`Boric Acid
`Sodium Borate
`Sodium Citrate
`Citric Acid
`Sodium Chloride
`Disodium Bdetate
`NaOH/HCI
`Purified Water
`
`Amount (wt. %)
`0.64% (w/v)
`0.225%
`0.08%
`0.46%
`0.016%
`0.48%
`0.05%
`pH 7.0
`QS 100
`
`EXAMPLE 7
`20
`The following formulation, which would contain one
`or more compounds of formula (I), may be utilized as a
`contact lens disinfecting solution, and would also aid in
`the cleaning of the lens.
`
`25
`
`Ingredient
`Boric Acid
`Sodium Borate
`Sodium Chloride
`Disodium Edetate
`Poloxamine
`NaOH/HCI
`Puri?ed Water
`
`Amount (wt. %)
`0.58%
`0.18%
`0.49%
`0.05%
`0.1%
`pH 7.0
`QS 100%
`
`What is claimed is:
`1. A preserved pharmaceutical composition compris
`ing an ophthalmic composition and an amount of a
`compound of the following formula effective to pre
`serve said ophthalmic composition from microbial con
`tarnination:
`
`30
`
`35
`
`40
`
`II
`R1-—c—NH—(cH2),.—N—(R2>2
`
`(I)
`
`45
`
`wherein:
`R1 is C6-C1g saturated or unsaturated alkyl, alkylaryl,
`or alkoxyaryl;
`n is 2 to 16; and
`R2 is C1-C3 saturated or unsaturated alkyl or alkanol,
`or a pharmaceutically acceptable salt thereof.
`2. A composition according to claim 1, wherein n is 2
`to 4.
`3. A composition according to claim 1, wherein R1 is
`heptadec-S-enyl, undecyl, undecenyl, pentadecyl or
`heptadecyl; and R2 is methyl, ethyl or hydroxyethyl.
`4. A composition according to claim 1, wherein R1 is
`heptadec-S-enyl, n is 2, and R2 is ethyl.
`5. An ophthalmic composition comprising an amount
`of a compound of the following formula effective to
`disinfect contact lenses:
`
`50
`
`55
`
`65
`
`wherein:
`
`5,393,491
`
`5
`
`15
`
`8
`R1 is C6—C13 saturated or unsaturated alkyl, alkylaryl,
`or alkoxyaryl;
`n is 2 to 16; and
`R2 is C1-C8 saturated or unsaturated alkyl or alkanol,
`or a pharmaceutically acceptable salt thereof; and a
`pharmaceutically acceptable vehicle therefor.
`6. A composition according to claim 5, wherein n is 2
`to 4.
`7. A composition according to claim 5, wherein R1 is
`heptadec-S-enyl, undecyl, undecenyl, pentadecyl or
`heptadecyl; and R2 is methyl, ethyl or hydroxyethyl.
`8. A composition according to claim 5, wherein R1 is
`heptadec-8-enyl, n is 2, and R2 is ethyl.
`9. A method of disinfecting a contact lens which
`comprises immersing the lens in an antimicrobial com
`position for a time sufficient to disinfect the lens, said
`composition comprising an amount of a compound of
`the following formula effective to disinfect the lens:
`
`I:
`R1—C-NH"(CH2)n-N_(R2)2
`
`a)
`
`wherein:
`R1 is C6-C18 saturated or unsaturated alkyl, alkylaryl,
`or alkoxyaryl;
`n is 2 to 16; and
`R2 is C1-C3 saturated or unsaturated alkyl or alkanol,
`or a pharmaceutically acceptable salt thereof; and a
`pharmaceutically acceptable vehicle therefor.
`10. A method according to claim 9, wherein n is 2 to
`
`4.
`
`11. A method according to claim 9, wherein R1 is
`heptadec-8-enyl, undecyl, undecenyl, pentadecyl or
`heptadecyl; and R2 is methyl, ethyl or hydroxyethyl.
`12. A method according to claim 9, wherein R1 is
`heptadec-8-enyl, n is 2, and R2 is ethyl.
`13. A method of preserving an ophthalmic composi
`tion which comprises including in the composition an
`amount of a compound of the following formula effec
`tive to preserve the composition from microbial con
`tamination:
`
`II
`R1—C—NH—(CH2),,—N—(R2)2
`
`(I)
`
`wherein:
`R1 is C6-C13 saturated or unsaturated alkyl, alkylaryl,
`or alkoxyaryl;
`n is 2 to 16; and
`R2 is C1-C3 saturated or unsaturated alkyl or alkanol,
`or a pharmaceutically acceptable salt thereof. 7
`14. A method according to claim 13, wherein n is 2 to
`4.
`15. A method according to claim 13, wherein R1 is
`heptadec-8-enyl, undecyl, undecenyl, pentadecyl or
`heptadecyl; and R2 is methyl, ethyl or hydroxyethyl.
`16. A method according to claim 13, wherein R1 is
`heptadec-S-enyl, n is 2, and R2 is ethyl.
`17. A method of cleaning a contact lens which com
`prises contacting the surfaces of the lens with a compo
`sition comprising an amount of a compound of the fol
`lowing formula effective to clean the lens:
`
`

`

`9
`
`wherein:
`
`5 , 3 93,49 1
`
`10
`R1 is C6-C13 saturated or unsaturated alkyl, alkylaryl,
`or alkoxyaryl;
`n is 2 to 16; and
`R2 is C1-C3 saturated or unsaturated alkyl or alkanol,
`or a pharmaceutically acceptable salt thereof; and a
`pharmaceutically acceptable vehicle thereof.
`18. A method according to claim 17, wherein the
`concentration of said compound is at least 0.01 wt. %.
`* * * * 1k
`
`5
`
`10
`
`15
`
`20
`
`25
`
`35
`
`45
`
`55
`
`65
`
`