US3459194A - Tobacco product incorporating a filter designed to inhibit the adverse effect of tobacco smoke on oral ubiquitous leucocytes - Google Patents

Description

B. EICHEL 3,459,194

TER DESIGNED TO INHIBT TOBACCO SMOKE Aug. 5, 1969 ff TOBACCO PRODUCT INCORPORATING A FTL THE ADVERSE EFFECT OF 0N ORAL UBIQUITOUS LEUCOCYTES Filed May 22, 1967 FIG.

FIG. 2

INVENTOR. 75l/5mm idd oQfAl/n m TTORNE Y United States Patent O U.S. Cl. 131-10 9 Claims ABSTRACT OF THE DISCLOSURE Novel tobacco filters comprising a filter bed of an ion exchange resin of suflicient length for inhibiting the adverse effects of tobacco smoke upon human oral leuocytes; and processes employing the salme.

BACKGROUND OF THE INVENTION Leucoytes present in the oral cavity and/or on the surface of oral tissues are held to play a major, and possibly a primary role in the natural defense mechanisms for preventing infection and various diseases and malfunctions resulting from the invention of foreign bodies through the oral cavity.

To illustrate the order of magnitude of this first line of body defense, parafiin stimulated human oral fluid [saliva]cell harvests yield at least five million to thirtythree million ubiquitous leucocytes of host origin per ml. of saliva contribution contained in such oral Huid-cell harvests; (For prior reports providing the basis for this perspective and findings, see, for example, Dental Abstracts, October 1964, p. 651; Journal of Society of Cosmetic Chemistry, vol. 15, 1965, pp. 149-154; Archives of Oral Biology, vol. 9, 1964, pp. 299-314; Journal of The American Society of Periodontists, vol. 1, No. 3, May/June 1963, pp. 109-117; and Journal of Dental Researc vol. 40, 1961, p. 747.)

The advantages, if not the necessity, for keeping such f cells healthy, e.g., viable, active, locomoting and phagocytizing, will be readily apparent. It will be equally as apparent that, Where possible, `one should avoid hinderance of these vital body defense mechanisms so as not to adversely affect maintenance of their normal healthy functional state.

SUMMARY OF THE INVENTION The present invention is directed to the discovery that the gaseous phase of tobacco smoke apparently acts adversely on these leucocytes, effectively precluding their ability to locomote and phagocytize in what is held to be a normal healthy manner, and to smoking filters which have been found to obviate the adverse effect to such cells normally caused by smoking.

According to the present invention, the normally adverse affect of smoking upon oral leucocytes is obviated by employing a filter comprising essentailly an ion exchange resin. If desired, the filters of this invention may 3,459,194 Patented Aug. 5, 1969 include the heretofore known means for filtering [ars and nicotine.

BRIEF DESCRIPTION OF THE DRAWING FIGURE l is a vertical view, partially in section, of a filtering device of this invention for use when smoking cigarettes or cigars;

FIG. 2 is a similar view of a filter cigarette including the novel filtering means of this invention; and

FIG. 3 is a similar view of a pipe containing a filter cartridge according to this invention.

DESCRIPTION OF PREFERRED EMBODIMENT In the preferred embodiment, the ion exchange resin employed as the filter bed or trap is a strong basic anion exchange resin present in a ybed of at least one inch in length, e.g., from 1-3 inches or longer, the diameter or thickness of the bed being on the order of a quarter of an inch or greater.

The filtering device preferably but not necessarily further includes any of the previously known means for removing substantial desired amounts of tars and nicotine.

As was mentioned previously, the present invention is directed to means for filtering tobacco smoke to prevent its adverse effect upon oral leucocytes and like host cells.

A primary object of this invention, therefore, is to provide novel products and processes for filtering tobacco smoke.

Another object is to provide novel filtering means for removing harmful substances from the gaseous phase of tobacco smoke.

Still another object is to provide novel cigarette, cigar and/ or pipe filters.

Yet another object is to provide a novel tobacco filter comprising essentially a bed of an ion exchange resln.

Other objects of the invention will in part be obvious and will in part appear hereinafter.

For a fuller understanding of the nature and objects of this invention, reference should be had to the following detailed disclosure taken in conjunction with the accompanying drawing.

In earlier work, e.g., as reported in Archives of Oral Biology, vol. 9, pp. 299-314 (1964), etc. and in accordance with the present invention, it has been consistently observed that in properly prepared oral fluid-cell harvests obtained from healthy individuals, most of the peripheral-wandering oral leucocytes are intact, alive and functional. In typical oral Huid-cell harvests, many of the leucocytes, free or contained in clusters, have been observed to locomote, vigorously extending pseudopodia, while demonstrating protoplasmic flow by pseudopod extension, cell stretching and movement of cell organelles internally. These leucocytes frequently have been observed to actively phagocytize large rod, chain, filamentous or other microorganisms. These important body defense mechanisms have been recorded dramatically in time lapse motion picture films. Employing the mouth (oral cavity) as a natural smoke trap, taking between 14 to 30 puffs without inhaling over a 2 to 3 minute period from an 85 mm. cigarette, I have observed that the leucocytes in a cluster or any given oral fluid cell harvest, samlcd from the same subject after smoking, often appear to verge on the brink of locomotion and possible phagocytosis, but these leucocytes remain incapable of overcoming the locomotion and phagocytosis-inhibiting effect of some toxic substance or substances provided by or present in tobacco smoke. In addition, the smoke obtained from puffing a single cigarette without inhaling has been found to be sufficient to inhibit appreciably the metabolism of oral fluid-cell harvests. For example in excess of 50% inhibition of the aerobic endogenous metabolish and aerobic glucose dependent oxidation, as measured by diminished oxygen consumption, has -been observed. In excess of 50% inhibition of the anaerobic metabolish, as -measured `by diminished CO2 evolution has also been observed.

The same adverse effects upon oral leucocytes have been determined when a cigarette is smoked through a conventional Cambridge CM113A (Cambridge Filter Corp.) filter which holds back all of the visible smoke, retaining in excess of 99% of the tars and nicotine and excluding virtually all taste and aroma associated with the tobacco smoke. Essentially, only the invisible gaseous phase of the smoke passes through this filter into the human mouth, thereby establishing that the probably harmful substance or substances] in tobacco smoke which so adversely affect the functional state of the oral leucocytes is present in the invisible gas-vapor phase and is not to any significant degree associated with the tar and nicotine fraction.

It has further been found, in accordance with this invention, that the aforementioned adverse effects of smoking upon oral leucocytes may be almost completely obviated by utilizing a tobacco filter comprising essentially a material such as an ion exchange resin, e.g., a strongly basic anion exchange resin such as Amberlite IRA-900 (trade name of Rohm & Haas Co. for a highly porous, type I, strong base, quaternary ammonium anion exchange resin possessing an extremely high fixed porosity); Dowex resins such as Dowex 1, 2, 1l or 21K (trade name of Dow Chemical Co., for strongly basic resins comprising a hydrocarbon network consisting essentially of a copolymer of styrene and divinylbenzene and incorporating a quaternary ammonium type of structure, Dowex 1, 11 and 21K being type I resins, the four substituents on the N atom being a polymeric benzyl and 3 methyl groups, Dowex 2 being a type II resin in which one of the methyl groups is replaced by an ethanol group); modified basic anion exchange resins such as that obtained by converting Amberlite IRA-401 (Rohm & Haas Co.) to the corresponding bicarbonate, etc.; or -a weakly basic anion exchange resin such as Dowex 3 (trade name of Dow Chemical Co. for a weakly basic anion exchange resin of the polyamine type), etc. Strongly basic anion exchange resins have been found to be most efiicient.

While basic anion exchange resins completely obviate the aforementioned adverse effects of tobacco smoke, acidic cation exchange resins have been found to exhibit some effect and hence are also considered as being useful filtering materials contemplated by this invetnion.

The novel smoking filters of this invention may be employed in the various manners in which tobacco filters have heretofore been employed. They may, for example, be employed in a holder adopted for use with cigarettes and/or cigars. FIG. 1 illustrates the use of the present invention in cigarette holders.

In this aspect of the invention, a holder of generally known construction is provided for use with a cigarette 12. Holder 10 comprises a hollow generally cylindrical element defined by a Wall member 14 of suitable strength and rigidity, eg., plastic or the like, tapering into a mouthpiece 16 of known construction for placement between the lips and having an opening for permitting egress of smoke from the holder to the mouth. The filter bed 18 of ion exchange resin is shown to be confined between opposed porous members 20 and 22 at some point between mouthpiece 16 and the opposed end 24. Members 20 and 22 may comprise any porous material, e.g., paper, plastic, porous methyl cellulose or various packed fibers sufficient to retain the resin, or they may comprise a perforated nonporous material. The internal circumference of the wall member 14 is slightly larger than the external circumference of cigarette 12 and is adapted for frictional engagement of the cigarette when inserted in the hollow portion of holder 10 at end 24 in juxtaposition with porous member 22. It will be appreciated that the distance |between member 22 and end 24 is a sufiicient length to engage cigarette 12 securely. When employed in a holder for use with a typical so-called regular, king size or greater size cigarette, e.g., -a cigarette on the order of 70 mm. or greater in length, the filter bed defined by porous members 20 and 22 is for optimum results at least one inch in length and most preferably on the order of 1.5, the diameter or thickness being approximately that of the tobacco bed in the cigarette, eg., on the order of a quarter of an inch. However, it is within the scope of the invention to employ filter beds of shorter length and thickness.

While for purposes of illustration, holder 10 has been shown as a cigarette holder, it will be appreciated that by varying the internal circumference defined by wall mem- Iber 14, the holder may be employed for cigars. It is contemplated that means (not shown) may be provided at end 24 for varying the circumference and/or for engaging either a cigarette or a cigar so that a single holder may be employed for both cigarettes and cigars.

When employed for use with cigars on the order of 6 or 7 inches in length, the filter bed is preferbaly on the order of 1-21/2 in length, the diameter or thickness being on the order of a quarter of an inch or greater.

While for purposes of illustration, the ion exchange resin is shown to be confined within the area defined by wall member 14, it may be contained initially in a cartridge or the like adapted for insertion within holder 10 in the manner shown. This latter construction permits ready substitution of filters when desired. The novel filter of this invention may also be incorporated into cigarettes and/ or cigars. FIG. 2 illustrates a lter cigarette in accordance with this invention. Such a cigarette 30 is shown to comprise wall members 32 and 34 defining a cigarette of typically cylindrical configuration. Wall members 32 and 34 may be of the same material, paper or the like, or may be different. They may consist of a single material extending from one end to the other or one may overlap the other and `be iadhered thereto in any of the known manners. Wall member 32 and porous members 38 and 40 define a filter bed 42 at one end of the cigarette. Members 38 and 40 may be the same as the previously described members 20 and 22 of the holder of FIG. 1. Member 38 is shown to be recessed from end 36 in a manner typical to so-called recessed filters, although the recessing of the filter bed is obviously not necessary to the practice of this invention. Tobacco 44 is shown to be confined between wall member 34 in the space defined by porous member 40 and end 46.

In a filter cigarette of the foregoing construction the ratio of the length of the filter bed, c g., as defined by members 38 and 40, to the length of the tobacco bed, e.g., as dened by member 40 and end 46, is preferably on the order of 1:3 to 1:2. Thus, for example, where the length of the tobacco bed is on the order of three inches, the length of the filter bed is preferably on the order of at least one to 1.5 inches, although greater and lesser lengths are also contemplated as useful.

Filter cigars of the general configuration shown in FIG. 2 are also contemplated. In ya filter cigar, the ratio of the length of the filter bed to the length of the tobacco bed is preferably on the order of 1:7 to 3:7. Filter cigarettes and/or cigars of the foregoing description may, if

desired, include a built-in mouthpiece to facilitate engagement between the lips.

The novel filter of this invention may also be employed as a cartridge or the like which may, for example, be inserted in smoking pipe stem, as shown in FIG. 3.

As shown therein, a conventional pipe 50 of known material 52 and construction deiining a mouthpiece 54, a stem 56 and a bowl 58 for tobacco 60 is shown to contain at some point between the mouthpiece and the bowl, a disposable or refillable cartridge or the like comprising a lter bed of ion exchange resin 62 confined with an area defined by outer wall member '68 of a suitable material, e.g. a thin heat polymerized plastic material, and porous end walls `64 and 66. The outer diameter of wall member 68 is slightly smaller than the internal diameter of pipe wall member 52 within the stern position of the pipe to preclude any material passage of smoke between the respective wall members, i.e., so that substantially all smoke must pass through the filter bed to mouthpiece 54. In this aspect of the invention, the pipe may be of one-piece construction, although typically it is not in order to provide ready access for cleaning and replacement of the filter cartridge, if needed. Such pipes are per se common and the general construction of the pipe accordingly comprises no part of this invention, the essence of this embodiment being the combination of a novel lter of this invention in a pipe of known configuration, e.g., as illustrated in FIG. 3.

The following examples show by way of illustration and not by way of limitation the practice of this invention.

Example 1.-Obtaining fluid-cell harvest yields Human oral fluid-cell harvest yields in the following examples were obtained by introducing into the mouth of the subject chewing paraffin and 5.0 ml. of a cold dextran harvesting uid. The subject chewed for 30 seconds and without swallowing expectorated all fluid into a graduated centrifuge tube.

Example 2.-Standardizing oral leucocyte yields `Oral leucocyte, epithelial cell, granular mass and bacteria counts were made on repetitive fluid-cell harvests from l2 subjects, male and female, smokers and nonsmokers ranging in age from l5 to 48 years.

The subjects were sampled at any arbitrary starting time having had nothing to eat, drink, chew or smoke, nor brushed the teeth or rinsed the mouth for at least one hour, the harvest yield being ydesignated the zero time uid-cell harvest. To achieve this, a piece of chewing paraffin and 5 .0 ml. of harvesting fluid was introduced into the oral cavity. As described in Example 1, the subject vigorously chewed for 30` seconds and without swallowing expectorated all fluid into a graduated centrifuge tube. Fluid-cell harvest yields for all subjects ranged between 5.5 ml. to 9.5 ml., indicating a `0.5 ml. to 4.5 ml. saliva tluid contribution from the mouth. This fluid volume yield for a given subject generally was consistent. Between the zero time fluid-cell harvest and each subsequent harvest the subject also was not permitted to eat, drink, smoke, chew, brush the teeth, or rinse the mouth. The subsequent oral iiuid-cell harvests were identified in accord with the sequence and time intervals that the samples were taken. For example, the second collection was obtained 5 minutes after the zero time uid-cell harvest to yield the 5 minute fluid-cell harvest. Ten minutes after the second collection, the minute fluid-cell harvest was obtained. The time intervals for subsequent collections were extended to yield in sequence, respectively, 20 minute, 40 minute and 60 minute fluid-cell harvests. Sampled in this manner, it was assumed that the l0 minute iluid-cell harvest cycled through a five minute recovery period and composition comparable to the 5 minute fluid-cell harvest plus being allowed an additional 5 minutes recovery time to approach the composition of the zero time fluid-cell harvest. In this manner the 60 minute uid-cell harvest thus cycled through a recovery period equivalent to that of the 5, 10, 20 and 40 minute fluid-cell harvests, respectively, plus being permitted an additional 20 minutes towards recovery.

The cell count patterns obtained, showed that the 40 minute oral fluid-cell harvests most frequently yielded the highest leucocyte counts. Where this did not occur, either the 60 minute harvests yielded the largest number of leucocytes, or the 40 minute and 60 minute samples yielded equally high leucocyte quantities. Leucocyte counts contained in the saliva contribution of such 40 minute and 60 minute oral fluid-cell harvests for the above group of subjects varied from about 5,000,000 per ml. to 33,000,- 000 per rnl.

Example 3.-Influence of tobacco smoke on aerobic and anaerobic metabolism under acute smoking conditions The aerobic endogenous and glucose dependent metabolism (O2 consumption) of 25 human subjects including smokers and non-smokers, male and female, ranging in age from 19 to 48 years were studied. During the course of these experiments, the need for modifying the above standard stampling procedure was recognized in order to provide a reasonable chance of quantitating a relatively reproducible effect of tobacco smoke upon the metabolism of the oral leucocyte from subject to subject. As a result the following procedure was adopted. Employing the information obtained from the leucocyte counts obtained in Example 2, the subject was required to rinse his or her mouth thoroughly with tap water two hours after eating, drinking, smoking, chewing, brushing of teeth, or rinsing of mouth. Then minutes later the subject bathed his or her mouth with the harvesting solution while chewing a piece of paran Ifor 30 seconds. This zero time oral fluidcell harvest was discarded. Forty-five minutes later this procedure was repeated and a 30 second oral fluid-cell harvest was collected .to yield a 0-45 minute control. Forty-two or forty-three minutes later the subject smoked an mm. standard brand filter cigarette taking 20 to 35 puffs without inhaling during the course of a three or two minute smoking period, respectively. When the smoking period was completed (precisely at forty-five minutes), another 30 second oral fluid-cell harvest was taken to yield a 45-90 minute experimental smoking sample. Fortyve minutes later a third 30 second oral fluid-cell harvest was taken to yield a -135 minute recovery control. This procedure was repeated for l2 subjects, 5 non-smokers and 7 smokers, in the most recent study group.

The tables set forth hereinafter report typical results of these procedures.

Table I, III, V, VII, and IX give the one and two hour O2 uptake activity values for aerobic endogenous and glu cose dependent metabolism for 2 non-smokers and 3 smokers, respectively. Tables II, IV, VIII, and X give the percent activities of the experimental smoking, recovery control harvests compared to the 0-45 minute control, the activities of which were assigned a value of percent in each instance.

In each case, the aerobic metabolism of oral fluid-cell harvests was substantially inhibited up to and in excess of 50 percent immediately following the smoking of one cigarette. In the case of the non-smokers, Tables I, II, III and IV, and young smokers, Tables V, VI, VII and VIII, the recovery sample tended to yield activities the same as or greater than the 0-45 minute control. In some instances the recovery sample activities remained depressed for the young smokers (data not summarized here). In the case of older long-term heavy smokers Tables IX and X (20 or smokers) recovery tended not to be complete or was more cigarettes per day and combined cigarettes and cigar strongly inhibited.

TABLE I.-AEROBIC ENDOGENOUS AND GLUCOSE DEPENDENT ME- TABOLISM OF ORAL FLUID-CELL IIARVESTS BEFORE AND AFTER SMOKING ONE STANDARD BRAND CIGARETTE Aerobic metabolism-O2 Uptake l Endogenous Endogenous Glucose activity plus glucose dependent activity activity 1hr., 2hrs., 1hr., 2hrs., 1hr., 2hrs., Oral fluid cell harvests pl. pl. pl. pl. pl. pl.

-45 Minute control 40 6G 75 151 85 4.590 Minute smoking 33 48 76 28 43 -135 Minute recovery 32 00 144 289 112 220 1 Per nilof oral fluid-cell harvest.

Subject 1, Non-smoker, male, 28 years, 35 pulls per 2 minutes without inhaling.

TABLE L-PERCENT ACTIVITY OF AFTER SMOKING AND RECOV ERY" HARVESTS COMPARED TO CONTROL HARVEST ASSIGNED A VALUE OF PERCENT Aerobic metabolism-O2 Uptake 1 Endogenous Endogenous plus Glucose.

activity glucose activity dependent activity 1 hr., 2 hrs., 1 hr., 2 hrs., 1 hr., 2 hrs., Oral fluid-cell harvests percent percent percent percent percent percent 0-45 Minute control 100 100 100 100 100 100 45-90 Minute smoking. 50 50 64 50 80 51 S10-135 Minute recovery 80 91 192 192 320 270 1 Per nil. of oral fluid-cell harvest.

Subject 1, Non-smoker, male, 28 years, 35 puffs per 2 minutes without inhaling.

TABLE IIL- AEROBIC ENDOGENOUS ANI) GLUCOSE DEPENDENT ME- TABOLISM OF ORAL FLUID-CELL HARVESTS BEFORE AND AFTER SMOKING ONE STANDARD BRAND CIGARETTE Aerobic metabolism-O2 Uptake l Endogenous Endogenous Glucose activity plus glucose dependent activity activity 1 hr., 2hrs., 1 hr., 2 hrs., 1 hr., 2 hrs., Oral Iluid cell harvests p1. pl. pl. p1. pl. pl.

0-45 Minute control 71 146 109 291 38 141:

45-90 Minute smoking 36 90 58 164 22 7o JO- Minute recovery 85 174 124 289 3) 115 1 Per inl. of oral l1uidcell harvest.

Subject 2, Non-smoker, male, 41 years, 24 pulfs per 2 minutes without inhaling.

TABLE IV.-PERCENT ACTIVITY OF AFTER SMOKING" AND RECOV- ERY IIARVESTS COMPARED TO "CONTROL" HARVEST ASSIGNED A VALUE OF 100 PERCENT Aerobic metabolism-O2 Uptake l 1 Per m1, of oral liuid cell harvest.

Subject 2, Non-smoker, male, 41 years, 24 puffs per 2 minutes Without inhaling.

TABLE V.-AEROBIC ENDOGENOUS AND GLUCOSE DEPENDENT ME- TABOLISM OF ORAL FLUID-CELL HARVESTS BEFORE AND AFTER SMOKING ONE STANDARD BRAND CIGARETTE Aerobic metabolism-O2 Uptake l Endogenous Endogenous Glucose activity plus glucose dependent activity activity 1hr., 2hrs., 1hr., 2hrs., 1hr., 2hrs., Oral liuid cell harvests p1. pl. pl. pl. pl. pl.

0-45 Minute control 39 6!) 48 103 9 34 45-90 Minute smoking. 19 40 28 66 4 17 90-135 Minute recovery. 24 38 45 96 21 51 1 Per nil, of oral fluid-cell harvest.

l sulbject 8, Smoker (40 cigarettes per day), iiiale, 23 years, 2G pulls per 2 minutes without in ia ing.

TABLE VI.-PERCENT ACTIVITY OF "AFTER SMOKING AND RECOV ERY HARVESTS COMPARED TO CONTROL HARVEST ASSIGNED A VALUE OF 100 PERCENT Aerobic metabolism-O2 Uptake 1 Endogenous Endogenous plus Glucose activity glucose activity dependent activlty,

1 hr., 2 hrs., 1 hr., 2 hrs., 1 hr., 2 hrs. Oral fluid-cell harvests percent percent percent percent percent percent -45 Minute control 100 100 100 100 100 100 45-90 Minute smoking.- 49 71 48 64 44 50 90-135 Minute recovery 62 55 94 93 223 150 1 Per nil of oral fluid-cell harvest.

in hject 8, Smoker (40 cigarettes per day), male, 23 years, 26 puis per 2 minutes without m a mg.

TABLE VIL-AEROBIC ENDOGENOUS AND GLUCOSE DEPENDENT ME. TABOLISM OF ORAL FLUID-CELL HARVESTS BEFORE AND AFTER SMOKING ONE STANDARD BRAND CIGARETTE Aerobic metabolism-02 Uptake l Endogenous Endogenous Glucose activity plus glucose dependent activity activity l hr., 2 hrs., 1 hr., 2 hrs., l hr., 2 hrs., Oral duid-cell harvests p1. al. pl. nl. nl.

0-45 Minute contro1 25 47 35 64 10 17 45-90 Minute smoking 14 31 20 32 6 1 90-135 Minute recovery 37 75 51 111 14 36 1 Per ml. of oral -uid-cell harvest.

uggject 9, Smoker cigarettes per day), female, 19 years, 20 puits per 2 minutes Without 1n a. mg.

TABLE VIII.PERCENT ACTIVITY OF AFTER SMOKING AND RE- COVERY HARVESTS COMPARED TO CONTROL HARVEST ASSIGNED A VALUE OF 100 PERCENT Aerobic metabolism-O2 Uptake 1 Endogenous Endogenous plus Glucose activity glucose activity dependent activity 1 hr., 2 hrs., 1 hr., 2 hrs., 1 hr., 2 hrs., Oral fluid-cell harvests percent percent percent percent percent percent 0-45 Minute control 100 100 100 100 100 100 45-90 Minute smoking 56 66 57 50 60 6 90-135 Minute recovery 150 160 146 173 140 212 1 Per ml. of oral duid-cell harvest.

ulhject 9, Smoker2(15 cigarettes per day), female, 19 years 20 puis per 2 minutes Without m a mg.

TABLE IX.-AEROBIC ENDOGENOUS AND GLUCOSE DEPENDENT IVIE- TABOLISM OF ORAL FLUID-CELL HARVESTS BEFORE AND AFTER SMOKING ONE STANDARD BRAND CIGARETTE Aerobic metabolism-O2 Uptake 1 Endogenous Endogenous Glucose activity plus glucose dependent activity activity l hr., 2 hrs., 1 hr., 2 hrs., 1 hr., 2 hrs., Oral fluid-cell harvests pl. p1. nl. 1. nl. ,111.

0-45 Minute control 56 86 92 211 36 12() 45-90 Minute smoking. 32 65 56 115 24 55 90-135 Minute recovery 29 38 52 94 23 56 1 Per m1. of oral fluid-cell harvest.

Subject 3, Smoker cigarettes and several cigars per day), male, 48 years 23 puffs per 2 minutes without inhailing.

TABLE )is-PERCENT ACTIVITY OF AFTER SMOKING AND RECOV ERY HARVESTS COMPARED TO CONTROL HARVEST ASSIGNED A VALUE OF 100 PERCENT Aerobic metabolism-O2 Uptake 1 Endogenous Endogenous plus Glucose activity glucose activity dependent actlvity 1 hr., 2 hrs., 1 hr., 2 hrs., 1 hr., 2 hrs., Oral uld-cell harvests percent percent percent percent percent percent 0-45 Minute control 100 100 100 100 100 100 -90 Minute smoking. 57 76 61 54 67 4U -135 Minute recovery 52 47 57 45 64 45 1 Per ml. of oral Huid-cell harvest.

Subject 3, Smoker (20 cigarettes and several cigars per day), male, 48 years, 23 pul's per 2 minutes without inhaling.

Example 4 Visualization of toxic inhibitory effects of tobacco smoke with time lapse phase contrast cinephotomicrography of oral leucocytes Control oral fiuid-cell harvests (Example 2) and harvests following smoking (Example 3) were observed by mounting a drop of the respective cell harvests contained in the oral fluid on a slide, sealing the cover slip with paraffin, and placing the slide under a phase contrast microscope. A cluster of leucocytes was sought and centered in the field as rapidly as possible. Time lapse photography was started as soon as this was done, The entire sequence was photographed at 2 second intervals, exposure time 0.5 second. Showing the resulting film at 16 frames per second yielded an impression of events 4() times faster than they occur as viewed by the observer through the microscope. The average time utilized for specific sequences varied from one to four hours. Each entire sequence was projected and examined in 90 to 360 seconds. [The film was preserved as a permanent record] For any given control (without smoking) oral fluidcell harvest, many of the leucocytes of a given cluster were seen to locomote vigorously, often giving the impression of furiously extending pseudopodia, while demonstrating interesting protoplasmic fiow by pseudopod extension, cell stretching and movement of cell organelles internally. Frequently, leucocytes were observed to be actively phagocytizing large rod, chain, filamentous or other oral micro-organisms. The overall effect was often quite dramatic.

In contrast, the leucocytes in a cluster of any given oral fluid-cell harvest, sampled immediately after any subject had taken between 14 to 30 puffs without inhaling during a 2 or 3 minute period from an 85 mm. cigarette without or with its filter or with a Cambridge CM113A filter, often appeared to verge on the brink of locomotion and possible phagocytosis, but almost every cell remained incapable of overcoming the locomotion and phagocytosis inhibitor effects of the toxic substances provided by the tobacco smoke. Most of the leucocytes of such clusters appeared to be frozen or immobilized and remained so throughout the sequence. At times, leucocytes at the periphery and within some of the clusters rounded and their granules exhibited the active brownian motion of the troubled leucocyte. Occasional exceptional leucocytes locomoted very sluggishly and attempted feeble phagocytosis. The overall effect was lacking in drama and in fact was often quite boring.

The foregoing examples establish unequivocally the adverse effect of the gaseous phase of tobacco smoke upon oral leucocytes.

The following examples illustrate how these adverse effects are obviated by means of the novel filter of this invention.

Example 5 The procedures described in Example 3 were repeated, employing in conjunction with the Cambridge CM 113A filter, a filter bed about one inch in length comprising an Amberlite IRA-900 strongly basic anion exchange resin. The smoke was thus caused to pass through both filters before entering the mouth. The oral fluid-cell harvests collected in the same manner immediately after smoking were found to contain healthy, viable, actively locomoting and phagocytizing leucocytes behaving in the same healthy functional manner as the control (no smoking) harvests described previously.

Example 6 Example 5 was repeated, substituting as the anion exchange resin, one prepared by passing a bicarbonate solution comprising 6 g. of sodium bicarbonate in 300 ml. of highly purified distilled water through a 1.0 inch "Amberlite IRA-401 resin bed at a rate of about 1.0 ml. drops) per minute, followed by thorough wash- 12 ing -with 500 ml. of highly purified distilled water. The results obtained were identical to those found in Example 5.

Example 7 The procedure described in Examples 5 and 6 was repeated, except that the Cambridge CM113A filter was eliminated. The results were substantially the same, indicating that the ion exchange resin bed may be used alone, and need not be employed in conjunction with other filtering means, e.g., filters for removing tars and nicotine, in order to obviate the effect of tobacco smoke upon the ubiquitous leucocytes.

While certain illustrative ion exchange resins have been mentioned previously and illustrative filter traps have been described in Examples 5 and 6, it will be appreciated that the invention is not limited thereto. Ion exchange resins are per se well known in the art and the selection of other such resins or other materials will accordingly be readily apparent to those skilled in the art in the light of the foregoing disclosure.

Since certain changes may be made in the above products and procedure without departing from the scope of the invention herein involved, it is intended that all matter contained in the above description or shown in the accompanying drawing shall be interpreted as illustrative and not in a limiting sense.

I claim:

1. A method for filtering from a tobacco bed source tobacco smoke intended for human consumption so as materially to decrease adverse effects on exposed ubiquitous, oral leucocytes incident to the smoking thereof which comprises interposing in the path of the smoke stream from said tobacco bed a strongly basic anion exchange or strongly acidic cation exchange resin bed at least ap proximately one inch in length and at least approximately A of an inch in diameter the quantity of the filter material to the tobacco being such as to result in the filtration of smoke to the point where substantially no observable inhibiting effect with regard to phagocytosis or motility on the said oral leucocytes occurs.

2. A process as defined in claim 1 wherein said filter bed is of substantially the same thickness as said tobacco bed.

3. A method for filtering tobacco smoke intended for human consumption so as materially to decrease adverse effects on exposed ubiquitous oral leucocytes incident to the smoking thereof which comprises interposing in the path of the smokescreen a resin filter bed comprising a strongly basic quaternary ammonium anion exchange resin which has been converted to the corresponding bicarbonate form, said resin bed being at least approximately one inch in length and at least approximately A inch in diameter, the quantity of said filter material to the tobacco being such as to result in the filtration of smoke to the point where substantially non observable inhibiting effect with regard to phagocytosis or motility on the said oral leucocytes occurs.

4. A process as defined in claim 3 wherein said tobacco and said resin bed are disposed in juxtaposition in the form of a unitary structure and constitutes a filter cigarette 5. A smokable product comprising a charge of tobacco and a filter element downstream therefrom interposed in the smoke stream between the tobacco charge and the mouth of the smoker, the said filter being selected from the group consisting of basic anion exchange resins, and acidic cation exchange resins, the said filter being at least approximately one inch in length and at least approximately 1A of an inch in diameter and consisting essentially of said resins and being in such quantity relative to the tobacco charge that substantially no observable adverse or inhibiting effect relative to motility or phagocytic ability of exposed ubiquitous oral leucocytes obtains.

6. The smokable product as defined in claim S in which the ion exchange resin comprises a strongly basic quaternary ammonium anion exchange resin which has been converted to the corresponding bicarboate form.

7. The smokable product as dened in claim 5 in which the tobacco charge and filter are assembled in a unitary structure so as to constitute a filter cigarette.

8. A iilter unit adapted to be associated with a smokable tobacco charge, said filter unit comprising a charge of an ion exchange resin selected from the group consisting of basic anion exchange resins and acidic cation exchange reins, said filter charge being at least approximately one inch in length and 1A; of an inch in thickness and consisting essentially of said resins and being in such quantity relative to the smokable tobacco charge with which it is to be associated that substantially no observable adverse effect relative to the motility or phagocytic ability of exposed ubiquitous oral leucocytes would obtain.

9. The iilter unit as defined in claim 8 in Which the said resin comprises a strongly basic quatemary ammonium anion exchange resin which has been converted to the corresponding bicarbonate form.

References Cited UNITED STATES PATENTS l 4 2,815,760 12/1957 Schreus et al 131-262 2,909,182 10/1959 Wilson et al 131-262 2,920,416 1/1960 Kinnavy 131-262 X 2,920,629 1/1960 Kinnavy 131-262 X 2,920,630 1/ 1960 Kinnavy 131-262 3,093,144 6/1963 Van Buuren 131-262 3,120,849 2/1964 Guttag 131--262 X 3,127,373 3/1964 Guttag 131-262 X 3,251,365 5/1966 Keith et al. 131-1'0.7

FOREIGN PATENTS 717,029 10/1954 Great Britain.

OTHER REFERENCES Tobacco-Experimental and Clinical Studies (1961) (Text), by Larson, Haagh and Silvette, pub. by The Williams and Wilkins Co. of Baltimore, Md., pages 112 and 563 esp. cited.

Smoking and Health, Report of the Advisory Committee to the Surgeon General of the Public Health Service, pub, by the U.S. Dept. of Health, Education and Welfare, pub. No. 1103, available U.S. Govt. Printing Oilice (1964), pp. 269 and 270 cited.

MELVIN D. REIN, Primary Examiner U.S. Cl. X.R. 131-1, 262

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