3,272,700
`United States Patent Office
`Patented Sept. 13, 1966
`
`1
`
`2
`
`3,272,700
`STABHLIZED AQUEOUS SOLUTION OF
`TETRACAINE SALT
`to
`Erwin S. Shppe, North Greenbush, N.Y., assignor
`Sterling Drug Inc, New York, N.Y., a corporation of
`Delaware
`No Drawing. Filed Oct. 3, 1963, Ser. No. 313,422
`1 Claim.
`(Cl. 167—52)
`
`This application is a continuation~in-part of my co-
`pending application Serial No. 167,955, filed January 22,
`1962, now ab-andonded.
`This invention relates to an improved aqueous solution
`of an acid-addition salt of 2-dimet-hylaminoethyl 4-n-
`butylaminobenzoate and to a method of maintaining
`clarity in said solution.
`also
`4-n-butylaminobenzoate,
`2-dimethylaminoethyl
`known generically as tetracaine,
`is a well-known com-
`mercial
`local anesthetic.
`It has been sold for almost
`twenty-five years in the form of its hydrochloride in aque-
`ous solution in various concentrations adapted for pro-
`longed spinal anesthesia, for surface anesthesia for dental
`practice, etc.
`’
`Manufacturers of such solutions, while enjoying com-
`mercial success over the years with these readily accepta-
`ble and efficacious aqueous prepar-ations have been at the
`same time faced with the persistent problem of how to
`increase the storage life of the solutions. On standing,
`these tetracaine solutions have the disadvantage of yield-
`-ing small quantties of precipitated 4-nbutylaminobenzoic
`acid, a hydrolysis degradation product of tetracaine. The
`4-n-butylaminobenzoic acid, which is relatively insoluble
`in aqueous solutions, separates as crystals 0-r produces
`cloudiness in the solution.
`.1 have now found that the precipitation of 4-n-butyl-
`sarninobenzoic acid from solutions of tetracaine salts, for
`instance the hydrochloride, is prevented by incorporating
`in the solutions a small quantity of an oxyethylated a1kyl-
`phenol-formaldehyde polymer. The resulting solutions,
`the composition aspect of my invention, have increased
`shelf life when stored for long periods at room tempera-
`ture (25° C.) and even at temperatures of 37°, 40° and
`50° C. or when heated as high as 121° C. for periods of
`one to three hours.
`The oxyethylated alkylphenol-formaldehyde polymers
`useful in the compositions o-f the invention are prepared
`by condensing a mole of an alkylphenol with 0.5-1.0
`mole of formaldehyde and reacting the product thus ob-
`tained with 8-60 moles of ethylene oxide, as described in
`U.S. Patent 2,454,541. Particularly useful polymers are
`the oxyethylated p - tertiary - octylphenol - formaldehyde
`polymers produced by condensing approximately equimo-
`lar amounts of p-tertiary-octylphenol and formaldehyde
`and then reacting the product with 10-20 moles of ethyl-
`ene oxide. A preferred compound of this group is the
`product containing ten ether groups per p-tertiary-octyl-
`phenol nucleus which is known under the brand names,
`“Superinone” and “Triton WR-1339,” chemically as oxy-
`ethylated tertiary octylphenol formaldehyde polymer or
`p-isooctylpoly-oxyethylenephenol
`formaldehyde polymer,
`and, generically as tyloxapol
`[1, Am. Med. Assoc., 181,
`243 (1962)]; the preparation of a closely similar and
`equivalently useful compound is described in Example 1
`of U.S. Patent 2,454,541, where-in eleven moles of ethyl-
`ene oxide are used.
`Aqueous solutions of the invention preferably have
`about 0.4 to about
`1 percent
`(weight per volume) of
`-
`an oxyethylated alkylphenol
`formaldehyde polymer.
`Greater quantities of the polymer, up to about 10 per-
`cent or more, can be used but to no particular advantage.
`Preferred embodiments are aqueous solutions containing
`about 0.1 to 2 percent of 2-dimethylaminoethyl 4-n-butyl-
`
`aminobenzoate hydrochloride and about 0.4 to 1 percent
`of tyloxapol. A particularly preferred embodiment con-
`tains 1.0 percent of tetracaine hydrochloride and 0.8 per-
`cent of tyloxapol.
`Another aspect of my invention resides in a method for
`maintaining clarity in an aqueous solution of a pharmaceu-
`tically-acceptable salt of 2-dimethylaminoethyl 4-n-butyl-
`aminobenzoate which comprises incorporating in said solu-
`tion normally subject to precipitation or cloudiness on
`storage an oxyethylated alkylp-henol-formaldehyde poly-
`mer in amount sufficient to keep the hydrolysis degrada-
`tion product 4-n-butylaminobenz-oic acid in solution on
`storage.
`-Preferred essential ingredients of said solution
`and preferred percentages thereof are presented herein-
`above.
`My invention is further illustrated by the following
`specific embodiments without, however, limiting it thereto.
`U.S.«P. grade ingredients are used in the following
`examples.
`
`Example I
`
`The following aqueous solutions containing 1 percent
`(weight per volume, i.e., 1 g. per 100 ml.) tetracaine hy-
`drochloride containing 0, 0.1, 1.0 and 10 percent tyloxapol
`were prepared:
`
`Ingredient
`
`1A
`
`1B
`
`1C
`
`1D
`
`10
`
`20
`
`25
`
`30
`
`1. 0
`Tetracaine hydrochloride. _ _ _
`0.67
`Sodium chloride ___________ __
`0.20
`Acetone sodium bisulI'1te___._
`Tvloxapol ........................... . .
`
`1. 0
`0. 67
`0.20
`0. 1
`
`1. 0
`0, 67
`0.20
`1. 0
`
`1. 0
`0, (37
`0. 20
`10.0
`
`The solutions were prepared by dissolving the ingredi-
`ents in distilled water and then were poured into 2 ml.
`flint ampuls, sterilized by heating at 220° F. for three
`minutes and stored at 122° F. (50° C.).
`The solutions were assayed for free 4-n4butylamino-
`benzoic acid (BABA) initially and after one and eight
`months storage at 50° C. with the following results:
`
`BABA, mg./ml.
`
`pH
`
`Preparation
`
`Initial
`
`1 month
`at 50° C
`
`8 months
`at 50° C.
`
`Initial
`
`Final
`
`40
`
`45
`
`50
`
`IA __________ __
`1B __________ __
`1C __________ __
`1D .......... ._
`
`0.015
`0.018
`0. 015
`0.019
`
`0.103
`0.119
`0. 150
`0. 105
`
`0.129
`0.139
`0. 378
`0. 429
`
`3. 5
`3. 4
`3. 5
`3.4
`
`3.53.1
`3.15
`3.08
`2. 61
`
`55
`
`60
`
`70
`
`None of the ampuls stored for 8 months at 50° C.
`showed any sign of crystallization after being allowed to
`cool and to stan-d at room temperature overnight. How-
`ever, on refrigerating at 5° C., some amorphous precipi-
`tate separated in the control (1A) and in the 0.1% tyloxa-
`pol solution (1B). No precipitate formed, even after
`a full week in the refrigerator, in the solutions containing
`1% (1C) or 10% (1D) tyloxapol.
`It is seen from the above results that 0.1% tyloxapol
`did not prevent the precipitation of BABA in the solu-
`tion containing 0.14 mg. -of BABA per ml. and that 1.0%
`tyloxapol did prevent the precipitation of as much as
`0.38 mg. of BABA per ml., the latter representing 3.8%
`decomposition of the tetracaine hydrochloride.
`It is also
`seen that 10.0% tyloxapol prevented the precipitation of
`0.43 mg. of BABA per ml., which represents only 4.3%
`decomposition of tetracaine hydrochloride.
`Petitioner |nnoP harma EX 1091
`
`|PR2015—00902
`
`|PR2015—0O903
`
`Page 1
`
`

`
`3,272,700
`
`4
`at 40° C. after submitting some of the ampuls for initial
`chemical assay.
`The results of the initial assay follow:
`
`Ingredient
`
`3A
`
`3B
`
`3C
`
`3D
`
`3E
`
`9. 69
`Tetrzicaiiie H01, mg./ml________ __
`Tyloxapol, mg./ml . _ . . . ..
`_ _ _ _ _ _ . _._
`-..
`BABA, mg./ml. _ ___
`0. 034
`
`DH............................._.
`3. 9
`
`9. 69
`2. 33
`0. 033
`3. 9
`
`9. 57
`4. 40
`0. 033
`3. 85
`
`9.67
`6.40
`0. 027
`3. 76
`
`9. 73
`8. 50
`0. 027
`3. 70
`
`The solutions stored at 40° C. were assayed for BABA
`after three and six months with the following results:
`
`Solution
`
`
`
`3 mo. at 40“ C.
`
`6 mo. at 40° C.
`
`12 mo. at 40° C.
`
`BABA,
`mg./ml.
`
`0. 11
`0. 11
`0. 11
`0. 11
`0. 11
`
`pH
`
`3. 80
`3. 80
`3. 80
`3. 75
`3. 70
`
`BABA,
`mg./ml.
`
`0. 10
`0.19
`0. 19
`0.20
`0. 30
`
`pH
`
`3. 75
`3. 80
`3. 80
`3. 70
`3.65
`
`BABA,
`mg./ml.
`
`pH
`
`0. 09
`0.21
`0. 31
`0. 32
`0.34
`
`3.68
`3. G9
`3. 81
`3. 60
`3. 58
`
`10
`
`15
`
`After storage for six months at 40° C., solutions 3B, 3C,
`3D and 3E remained clear and solution 3A yielded crys-
`tals when chilled for two hours in an ice bath. After
`storage for twelve months at 40 C., solutions 3C, 3D
`and 3E remained clear and solutions 3A and 3B yielded
`crystals when chilled for five hours in an ice bath.
`
`Example 4
`
`The following solution containing 0.15 percent tetra-
`caine hydrochloride and 0.8 percent of tyloxapol was pre-
`pared:
`
`Mg./ml.
`Ingredient:
`Tetracaine HCI ________________________ __
`1.5
`Sodium chloride _______________________ __
`8.6
`Calcium chloride-2H2O _________________ __ 0.33
`Potassium chloride _____________________ __ 0.30
`Tyloxapol _____________________________ __
`8.0
`
`The anesthetic and the three inorganic chlorides were
`dissolved in most of the distilled water, the tyloxapol
`added and dissolved, the pH adjusted to 5.2 by addition
`of 0.1 N sodium hydroxide solution, and the remaining
`water added. The solution was filtered through an ultra
`fine frit glass filter into a sterile system and then filled
`into 100 ml. glass stoppered flint vials. The vials were
`heated at 220° F. for thirty minutes and stored at 37° C.
`for twelve months. Assays initially and after six and
`twelve months are summarized as follows:
`
`Ingredient
`
`Initial,
`mg./ml.
`
`6 mo./37° C.,
`mg./ml.
`
`12 mo./37° C.,
`mgnlml.
`
`1 46
`7 6
`0 034
`4 2
`
`1.32
`0.6
`0.056
`4.45
`
`1.48
`8.0
`0.015
`5.5
`
`
`
`Tetracaine
`Tyloxapol
`BABA.-.
`pH..................... --
`
`The solution after twelve months at 37° C. was clear
`and colorless.
`
`30
`
`40
`
`45
`
`55
`
`60
`
`3
`Example 2
`
`tetracaine hy-
`The following solutions of 1 percent
`drochloride containing 0, 0.2, 0.4,
`‘0.6 and 0.8 percent
`tyloxapol were prepared:
`
`Ingredient
`
`2A
`
`2B
`
`2C
`
`2D
`
`2E
`
`5.0
`3. 35
`1. 0
`4.0
`500
`
`5.0
`3. 35
`1. 0
`2.0
`500
`
`5. 0
`3. 35
`1. 0
`3.0
`500
`
`5.0
`3. 35
`1. 0
`1.0
`500
`
`
`
`5. 0
`Tetraeaine hydrochloride,
`_ 3. 35
`Sodium chloride, g ______ ._
`1. 0
`Acetone sodium bisulfite, g
`_ ____ ._
`Tyloxapol, g ________________ ,_
`500
`Water for injection. rnJ., q.s. ad ______ __
`
`Each of the above solutions was prepared as follows:
`The acetone sodium bisulfite was dissolved in about 400
`ml. of distilled water containing the tyloxapol. The so-
`dium chloride and tetracaine hydrochloride were then
`dissolved, respectively; and the pH of the solution was
`checked and adjusted to 4.6. Distilled water was added
`to give 500 ml. of solution which was filtered through
`an ultra fine frit glass filter into a sterile system and then
`filled into 2 ml. flint ampuls under aseptic conditions.
`The ampuls were heated at 220° F. for three minutes,
`submitted for chemical assay and some were then stored
`at 40° C., some in a refrigerator (about 5° C.) and some
`at room temperature (about 20-25 ° C.).
`The results of the initial assay are summarized as fol-
`lows:
`
`Ingredient
`
`2A
`
`2B
`
`20
`
`2D
`
`2E
`
`9. 6
`7. 30
`O. 025
`2. 90
`
`9. 7
`9. 7
`9. 7
`9. 5
`Tetracaine HC1, mg.lm1_____________ __
`5. 50
`4. 6
`Tyloxapol, rrig.lml. _ ___...
`_______ ._ 2. 35
`BABA, mg./ml________ ..
`-__ O. 022 0. 024 0. 025 0. 024
`pH__________________________________ ._ 3. 35
`3. 00
`2. 95
`2. 90
`
`
`
`The solution stored at 40° C. were assayed for BABA
`after three and six months with the following results:
`
`Solution
`
`3 me. at 40° C.
`
`6 mo. at 40° C.
`
`BABA,
`mg./ml.
`
`pH
`
`BABA,
`mg./ml.
`
`pH
`
`
`
`0. 098
`O. 159
`0. 167
`0. 171
`0. 171
`
`3. 05
`2. 95
`3. 00
`3. 00
`3. 05
`
`0. 103
`0. 202
`0. 253
`0. 283
`0. 292
`
`3. 05
`2. 95
`2. 95
`2. 90
`2. 88
`
`After storage for six months at 40° C., solutions 2C,
`2D and 2E remained clear and solutions 2A and 2B
`yielded crystals when chilled for six hours in an ice bath.
`Thus, it is seen that 0.2% tyloxapol did not prevent the
`precipitation of BABA in the solution containing 0.20
`mg. of BABA per ml. and 0.4%, 0.6% and 0.8% tyloxa-
`pol did prevent the precipitation of as much as 0.25 mg.,
`0.28 mg. and 0.29 mg., respectively, of BABA per ml.
`Example 3
`
`The following solutions of 1 percent tetracaine hydro-
`chloride containing 0, 0.2, ‘0.4, 0.6 and 0.8 percent tyloxa-
`pol were prepared as in Example 2 but adding a lactic
`acid-sodium lactate buffer:
`
`
`Example 5
`Ingredient
`3E
`3D
`30
`3B
`3A
`“‘"j“‘”’—___‘: 65
`Following the Procedure described in Exa‘mp1e_2,the
`”s”.3.§l;‘.$:“é‘i?i35.i‘3a‘.4,%:::::::""" 0. 30?
`0.322
`0.322
`0.322
`0.322
`following solution containing 1.0 percent tetracaine hy-
`Acetone sodium bisulfite,
`0.5
`0.5
`0.5
`0.5
`0.5
`drochloride and 0.80 percent of tyloxapol was prepared:
`gg’d1{’lffif’f,};,tga't5'(6'd.%3:‘;,;1'
`_ “'i_'5‘
`(1):?
`kg
`§:g
`'
`-
`391' 01' 1180 01],
`.s.a ,]I1 ___
`»%“%“°i“°‘? ‘85£i”’”“““a""i"" °’3§8
`°'3§3
`° 323
`“SE8
`Adjusted pI'I......3...........-.
`3.98
`4.05
`4. 03
`4.03 7° HC1 __________________________g_Q2“",‘5‘(‘)t_‘ég
`Tyloxapol ____________________________ __g__ 40,00
`Sodium chloride _______________________ __g__ 33.50
`The pH was adjusted to the above values using lactic
`Acetone sodium bisulfite ________________ __g-_ 10.00
`acid. The solutions were filled into sterile 2 ml. flint
`ampuls, heated at 220° F. for three minutes and stored 75 Water for injection, q.s. ad _____________ __m1__ 5000
`
`
`
`“"328
`4.05
`
`Page 2
`
`
`
`Page 2
`
`

`
`3,272,700
`
`Ca‘!
`
`10
`
`15
`
`6
`by standard procedures and the presence of the tyloxapol
`in the solutions was found not to have any significant
`change on the local anesthetic activity, toxicity, or irritan-
`cy when compared with corresponding solutions with-
`out
`the tyloxapol. For example,
`the average duration
`of urethral anesthesia in rabbits was 137:9.0 minutes
`for
`1.0 percent
`tetracaine hydrochloride alone and
`1611193 minutes for 1.0 percent tetracaine hydrochlo-
`ride with 1.0 percent tyloxapol; these data show that the
`addition of tyloxapol had slight if any effect on dura-
`tion of anesthesia by tetracaine hydrochloride alone. Sim-
`ilarly, no significant change in local anesthetic activity
`occurred when 1 percent tyloxapol was added to a 0.25
`or 0.50 percent tetracaine hydrochloride solution when
`tested by the intradermal wheal test in guinea pigs.
`The acute oral toxicity in mice of tetracaine hydrochlo-
`ride plus a 2 percent aqueous solution of tyloxapol was
`not significantly different from that of tetracaine hydro-
`chloride in distilled water without tyloxapol. When a
`25 percent aqueous solution of tyloxapol alone was studied
`for toxic effects in mice, no deaths occurred with oral
`doses as high as 10,000 mg./kg.,
`i.e., LD,-,0 >10,000
`mg./kg.
`The acute intravenous LD,-,0 determinations in mice car-
`ried out with 1.0 percent tetracaine hydrochloride alone,
`with 1.0 percent tetracaine hydrochloride containing 1.0
`percent tyloxapol, and with 0.25 percent tetracaine hydro-
`chloride containing 1.0 percent tyloxapol were respective-
`ly: 6.7:0.7, 6.3-$0.6 and 62:06 mg./kg. in terms of
`tetracaine hydrochloride. Thus, the addition of tyloxapol
`to tetracaine hydrochloride, in the concentrations studied,
`had no significant effect on the acute intravenous LD50
`for tetracaine hydrochloride in mice. When a 25 per-
`cent concentration of tyloxapol alone was studied intra-
`venously for toxic effects in mice, the LD5o was >10,000
`mg./kg.
`The solution embodiment of my invention described
`above in Example 5 (also as Examples 2E and 6B) has
`been studied clinically by leading anesthetists accustomed
`to doing spinal anesthesias. These investigators tested the
`solution in 420 patients ranging in age from 13 to 89
`and found it
`to be safe and effective for its intended
`purpose. They obtained good results with 384 patients,
`fair results with 31 patients, and poor results with only
`45 5 patients; side effects were mild and were observed in
`
`20
`
`25
`
`30
`
`35
`
`40
`
`5
`Results of the initial assay and assays after storage at
`37° C. for twelve months and at room temperature (25°
`C.) for twenty-three months are given as follows:
`
`Ingredient
`
`Initial
`
`12 mo., 37° C.
`
`23 mo., 25° C.
`
`9.38
`8.42
`0.23
`3.68
`
`9. 22
`8.4
`0.31
`3. 50
`
`9. 64
`Tetracaine H01, mg./ml
`7.94
`Tyloxapol, mg./ml.---
`- ________ __
`BABA, mg./ml_____
`3. 70
`pH _______________________ ..
`
`
`
`The two stored solutions were clear and colorless after
`the storage periods. Also, the same solution was stored
`for thirty-four months at 25° C., was next heated at 250°
`F. for twenty minutes, and, on assay, was found to con-
`tain only 0.26 mg./ml. of BABA and to have a pH of
`3.70.
`this embodiment gave good results
`As noted below,
`when tested clinically.
`
`Example 6
`the following
`For comparative heat stability studies,
`solutions of 1 percent tetracaine hydrochloride containing
`0 and 0.8 percent tyloxapol were prepared, the former
`solution (6A) being a presently commercial preparation
`and the latter (6B) being a preferred embodiment of my
`invention.
`
`Ingredient
`
`6A
`
`6B
`
`1. 00
`0.80
`0.67
`0.20
`100.00
`
`1.00
`Tetracine H01, g________________________ ._
`Tyloxapol, g_ . _ _ _ _ _
`_ _ _ _ _ . . . _ _ _ _ _ _ _ . __
`Sodium chloride, g_________ __
`0.67
`Acetone sodium bisulfite, g._
`0.20
`Water for injection, m1., q.s. a ___
`100.00
`
`
`
`These solutions were prepared following the procedure
`described in Example 2 and in addition to heating some
`of the ampulled solution at 220° F. for three minutes,
`as in Example 2, some of the solution was assayed with
`no heating and some assayed after heating for different
`times indicated below. My solution with tyloxapol as-
`sayed as follows:
`
`Solution 6B
`
`Not
`Heated
`
`220° F.,
`3 min.
`
`121° 0.,
`15 min.
`
`121° 0.,
`30 min.
`
`121° 0.,
`45 min.
`
`121° (3.,
`60 mm.
`
`Tetracaine HC1, mg./ml.
`Tyloxapol, mg./ml_____..
`BABA, mg./ml . _ _ _ _
`_ _.
`
`
`pH
`
`9.9
`8.2
`0. 012
`3. 35
`
`9.8
`8. 2
`0.014
`3.15
`
`9. 8
`8. 2
`0. 029
`3.15
`
`9. 7
`8.2
`0. 042
`3.15
`
`9. 8
`8. 2
`o. 053
`3.15
`
`9. 7
`8.2
`0. 059
`3.15
`
`The commercial preparation with no tyloxapol assayed
`as follows:
`
`55 only a small number of patients, e.g., mild hypotension
`(7), nausea (4), vomiting (11) and headache (1).
`
`Solution 6A
`
`Not
`Heated
`
`220° F.,
`3 min.
`
`121° 0.,
`15 min.
`
`121° C.,
`30 min.
`
`121° C.,
`45 min.
`
`121° _C.,
`60 mm.
`
`Tetracaine HC1, mg./ml.
`BABA ________________ __
`pH ____________________ _.
`
`9. 7
`0. 010
`3. 40
`
`9. 8
`0. 013
`3. 70
`
`9.9
`0.032
`3. 70
`
`9.8
`0. 044
`3. 60
`
`9. 7
`0.059
`3. 60
`
`a9. 7
`0. 072
`3. 50
`
`- Crystal formation when chilled in refrigerator (about 4° 0.).
`
`From the above results, it is noted that the presence of
`tyloxapol did not induce the hydrolysis of the tetracaine,
`the BABA concentrations being about the same for the
`two solutions when treated the same. However, the prep-
`aration with no tyloxapol (6A) showed crystal forma-
`tion when heated at 121° C. for sixty minutes and then
`stored in a refrigerator (about 4° C.) for a few days.
`In contrast, my solution (6B) even when heated at 121°
`C. for as long as three hours and then stored in a refrig-
`A stabilized aqueous solution of a pharmaceutically-
`erator for a few days showed no crystal formation.
`acceptable acid-addition salt of 2-dimethylaminoethyl 4-
`The aqueous solutions of my invention were tested 75 n-butylaminobenzoate having as the stabilizing agent be-
`
`Other aqueous local anesthetic solutions can be pre-
`pared in accordance with the foregoing description by
`using,
`in addition to the essential
`ingredients of tetra-
`caine hydrochloride and oxyethylated alkylphenol-form-
`aldehyde polymer, other anesthetics, preservatives, buf-
`fering agents, etc., provided they are mutually compatible
`with the essential ingredients of the solution.
`I claim:
`
`70
`
`Page 3
`
`Page 3
`
`

`
`3,272,700
`
`7
`tween about 0.4 to about 1.0 percent tyloxapol per 0.1
`to 2 percent of said benzoate.
`
`2,637,679
`2,649,918
`2,880,138
`
`References Cited by the Examiner
`UNITED STATES PATENTS
`5/1953 Gaunt ____________ __ 167——~58
`8/1953 Miller ____________ __ 167—58
`3/1959 Johnson __________ __ 167——65
`OTHER REFERENCES
`
`Clark, Chem. Abst., volume 48, pages 10937-10938,
`1954.
`
`8
`Drill, Pharmacology in Medicine, sec. ed., McGraw-
`Hill, 1958, page 106.
`Monash, Arch. Dermatol., vol. 76, No. 6, pages 752—
`756, December 1957.
`Sisley, Encyclopedia of Surface-Active Agents, Chem.
`Pub. Co., 1952, pages 538-539.
`
`C!
`
`JULIAN S. LEVITT, Primary Examiner.
`
`10 FRANK CACCIAPAGLIA, J11., Examiner.
`
`Page 4
`
`
`
`Page 4
`
`

`
`UNITED STATES PATENT OFFICE
`
`CERTIFICATE OF CORRECTION
`
`Patent No. 3,272,700
`
`September 13,
`
`15
`
`Irwin S. Shupe
`
`It is hereby certified that error appears in the above numbered pat-
`ent requiring correction and that the said Letters Patent should read as
`corrected below.
`
`line 30, for "quantties” read —- quantities ——;
`Column 1,
`column 3,
`line 69, fourth Table,
`third co1umn,1ine 6, for
`”0.975" read —— 0.075 —e; columns 5 and 6, fourth Table,
`seventh column,
`line 1, for “39.7” read —— 9.7 --;
`same column
`line 2, for ”0.072” read -— 30.072 ——.
`
`Signed and sealed this 5th day of September 1967.
`
`(SEAL
`Ancst:
`
`ERNFSfl"WCS“HDER
`Attesting Officer
`
`II“VARD.L BBI$UUfl{
`Commissioner of Patents
`
`Page 5
`
`Page 5