WO2011018784A1

WO2011018784A1 - Package for alternating medications

Info

Publication number: WO2011018784A1
Application number: PCT/IL2010/000641
Authority: WO
Inventors: Rephael Mohr; Asaf Mohr
Original assignee: Rephael Mohr; Asaf Mohr
Priority date: 2009-08-12
Filing date: 2010-08-08
Publication date: 2011-02-17

Abstract

A method and apparatus for directing a patient to a non-daily medication regimen, comprising serially providing at least two different sorts of drugs for alternating successive periodic intake.

Description

PACKAGE FOR ALTERNATING MEDICATIONS

FIELD OF THE INVENTION

The invention relates to packaging of medications. Some embodiments of the invention relate to packages for dispensing medications on a non-daily basis.

BACKGROUND OF THE INVENTION

Statins (HMG-CoA reductase inhibitors) are a class of drugs frequently indicated for people with a risk of cardiovascular disease in order to lower their cholesterol levels. In many cases, antiplatelet or anti-clotting drugs are also indicated to such persons in order to decreases platelet aggregation and inhibit thrombus formation. Often, a person is prescribed for a daily intake of the two drugs, one of statin and one of antiplatelet (as disclosed, for example, in Br J CHn Pharmacol. 2008 July; 66(1): 110-116).

Some statins have half-life period of about 24-hours, for example, third generation atorvastatin (Lipitor) or rosurvastatin (Crestor), as disclosed in Int. J. CHn. Pract., October 2004, 58, 10., p.947.

As disclosed in a few publications, antiplatelet drugs such as aspirin (acetylsalicylic acid) or plavix (clopidogrel) have shorter half-life than the statins mentioned above, but due to irreversible effects the lifespan is increased to several days. Aspirin half-line is about 15-20 minutes but because its effect on platelets is irreversible, the duration depends on the life span of the platelets, resulting in a pharmacological half-life of about 6 days (e.g. Therapeutics Letter, 37, September- October 2000). Plavix half-life is about 8 hours but has an irreversible effect on platelets with a lifespan of approximately 7-10 days (e.g. Jarvis B. Simpson K. Drugs, Volume 60, Number 2, August 2000 , pp. 347-377(31)).

Statins and antiplatelet drugs might have side effects. A side effect of statin is disclosed, for example, in Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco A, Littarru G, J CHn Pharmacol 33 (3): 226-9. PMID 8463436, and a side affect of aspirin is disclosed, for example, in Sørensen HT, Mellemkjaer L, Blot WJ et al, Am. J Gastroenterol. 95 (9): 2218-24. doi: 10.1111/j.1572- 0241.2000.02248.x. PMID 11007221.

Several publications suggested using statins on alternating days, for example, Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 8, No. 2, 123-126 (2003), or American Heart Journal 144(4) October 2002 pp 674-677, or The Anatolian Journal of Cardiology, 2008:8 407-12. Using antiplatelet drugs as aspirin or plavix on alternating days was also suggested, for example, Agency for Healthcare Research and Quality, July 2007 (www.meps.ahrq.gov/mepsweb /datajiles/publications/stl 79Zstatl79.pdf) or Circulation. 2003;108:e56 or BMJ 2004; 328: 477-479.

There has been an attempt to offer statins (pravastatin) and antiplatelet (aspirin) as pairs of pills in a package (PRAV1GARD™ PAC by Bristol-Myers Squibb Company), seemingly without a remarkable success as its sale, at least in the US, was discontinued (www. rphlink. com/pravigard) .

SUMMARY OF THE INVENTION

A general underlying aspect of the invention relates to a regimen of non-daily intake of a medication, that is, alternating days regimen such as once per two days or once every three days.

For example, alternate intake of statin and antiplatelet medications on alternating days - instead of a regimen of taking both statin and antiplatelet medications on a daily basis.

A suggested rationale for alternating days regimen is that persons having a risk such as of cardiovascular disease are frequently prescribed with both statin and antiplatelet drugs. Owing to the pharmacological half-life period of about 24-hours of atorvastatin and rosurvastatin statins, and to the pharmacological half-life period of several days of aspirin and plavix antiplatelet drugs, these medications may still be effective over a period such as two days, thereby, optionally, reducing the side effects of one or both of the medications, and optionally also reducing the costs for the patient.

In some embodiments, the dose of one or both of the medications in alternating days regimen, such as of statins and antiplatelet, are modified relative to a daily intake of a medication. For example, the dose of an antiplatelet drug is increased to prolong or increase the therapeutic effect over two days, or the dose of a statin drug is increased to extend the pharmacological effect to about 48-hours.

In some embodiments of the invention, a typical alternating days regimen is, for example, statin on day 1, antiplatelet on day 2, etc. Optionally or alternatively, alternating days regimen comprises other combinations of daily intake of statins and antiplatelet drugs. For example, aspirin and plavix on day 1, statin on day 2, etc., or aspirin on day 1 and statin and plavix on day 2, etc., or other combinations such as plavix on day 1 and statin and plavix on day 2, etc.

In some embodiments of the invention, only a specific drug is to be taken on alternating days without a complementary drug on complementary days, for example, on day 1, day 3, etc. Yet, in order to preserve a daily intake, a placebo drug is taken on the complementary days, such as with respect to the preceding example, on day 2, day 4, etc.

An aspect of the invention related to a method for directing a patient (user) to a non-daily regimen of medication. In some embodiments of the invention, two or more different sorts of drugs are provided in a series for daily (or for other recurring period) alternating successive intake. Optionally, at least one drug is provided as a placebo for intake when the medication is not required, thereby marinating a daily (or other recurring) intake by the patient.

An aspect of the invention relates to an apparatus for directing a patient to a non-daily regimen of medication in some embodiments of the invention, the apparatus is a package for storing or storing pills (drugs) for dispensing the pills to a patient, formed to direct or assist the patient to take different sorts of pills in successive and sequential order, typically on alternating days. For example, statin on day 1, antiplatelet on day 2, statin on day 3, antiplatelet on day 4, and so on, or for example, statin on day 1, placebo on day 2, statin on day 3, placebo on day 4, and so on, or for example, antiplatelet on day 1, placebo on day 2, antiplatelet on day 3, placebo on day 4, and so on.

In some embodiments of the invention, a package directing or assisting the patient comprises and/or presents and/or displays one or more of text, marking, color, shape, symbol, or a combination thereof on the package. Optionally or additionally, the package comprises one or more components having one or more shapes or colors to direct or assist the patient to alternate between the pills.

In some preferred embodiments of the invention, the pills are evenly stored in a package to have an equal number of the drugs, for example, statin and antiplatelet pills (up to an extra pill in case of odd number of pills per package). Optionally and preferably, the pills are stored in the package in the prescribed order of alternate pills in alternating days (e.g. statin, antiplatelet, statin, antiplatelet, etc.), thereby further directing or indicating the sequence or alternating drugs.

In some embodiments of the invention, the package is formed such that to pick pills within the package is more difficult or intricate relative to separating a segment of the immediate candidate pill and picking the pill out of the separated segment.

In some embodiments of the invention, the package comprises a structure that obstructs or blocks or impedes picking a pill from the package, such as the next candidate pill, before the immediate candidate pill to be taken was picked, thereby assisting or directing the patient (user) on the order of intake.

In some embodiments of the inventions, the package is structured and/or comprises material or materials that, optionally excluding the immediate candidate, prevents or impedes picking of the pills. However, picking the immediate candidate pill initiates a process and/or mechanism that allows, or enables, or eases picking the next candidate pill only after a period of time, for example, after approximately 24 hours, thereby requiring and/or compelling the patient to adhere to the alternating days regimen.

Optionally or additionally, the package about the non-immediate candidate is colored (or otherwise marked, e.g. by text) to indicate that the pills are not yet due (e.g. by red color), and picking the immediate candidate pill initiates a process and/or mechanism that colors (or otherwise marks) the package about next pill after a period of time, such as about 24 hours, with an indication that this pill is due (e.g. by green color).

In preferred embodiments of the invention, without limiting, the package or packages are provided as a set of one or more sheets with blisters or bubbles or other compartments for storing and picking the pills. Preferably, without limiting, the compartments are at least partially transparent so that the pills are visible. Optionally, in some embodiments, the statin and antiplatelet pills have different shape and/or color and/or marking. Optionally or additionally, the compartments of the statin and antiplatelet pills have different shapes, preferably corresponding to the pills' shape.

In some preferred embodiments of the invention, a statin drug comprises one of atorvastatin or rosurvastatin and the antiplatelet comprises one of aspirin or plavix.

In some embodiments of the invention, the package is provided by the drugs manufacturer or a related packing organization. Optionally or alternatively, the patient fills the pills into a custom-made package, optionally using a particular tool that facilitated convenient filling in the proper order.

In the specification and claims the following terms and derivatives and inflections thereof imply the respective non-limiting characterizations below.

Daily (regimen) - recurring every day, or every certain lapse of time such as every 8 hours.

Alternating (days) - sequentially every other day, yet not precluding every three days or more (e.g. one pill on day 1, then day 4, etc. and the other pill on day 2, day 5, day 8, etc.).

Direct (the patient) -comprising also guide, or prompt, or indicate, or suggest or assist.

Blister - or bubble, or any compartment in a package that stores a pill for dispensing.

Picking (a pill) - removing a pill out of a compartment that stores the pill, such as pushing a blister and ripping a foil beneath it. In some case, picking a pill involves separating a segment of the package that stores that pill.

Immediate candidate (pill) - the pill due for intake, such as today (or a related structure thereof).

Next candidate (pill) - the pill to be taken after the immediate candidate pill

(or a related structure thereof).

Segment (regarding a pill) - a segment of the package storing a specific pill (rather than a segment of the pill itself).

Evenly (stored) - having an equal number of statin and antiplatelet pills - up to an additional one of the pills in case of odd number of pills in a package.

Indentation - including one or more of perforations, or notches, or grooves, or partial cuts, or other structure or structures facilitating convenient breaking of segment off a package (resembling the divisions on a chocolate bar).

Complementary (drug or day) - relates to a other day or day in the alternating days regimen.

Placebo - relates to a composition having no medical effect or negligible effect, optionally having a strengthening or other effect on the complementary drug in the alternating days regimen. The terms 'medication', 'pill' 'tablet', 'serving' or 'drug' are used herein interchangeably denoting according to the context, without limiting, a composition or a composition in a given amount.

It should be emphasized that, without limiting, the term 'day' is used herein to denote a period or specific time of day, such as 24 hours, 12 hours, or 6 hours or morning and evening. For example, alternating 'days' can denote morning and afternoon, so that a sequence of day 1, day 2, day 3 and so on denotes morning, afternoon, morning and so on, or can denote morning, noon, evening, morning and so on. Optionally, the periods are not equal, for example, 12 hours, 6 hours, 12 hours and so on.

It should be noted that referring to packages storing pills does not preclude corresponding packages for corresponding storage and use, even before pills are stored or filled therein.

According to an aspect of some embodiments of the present invention there is provided a package for storing pills for dispensing to a patient, comprising at least two compartments for storing pills of at least two different sorts, each compartment for at least one pill, wherein the package is formed to direct the patient to successively alternate between pills of a different sort.

In some embodiments, a pill of one sort is stored after a pill of another sort in a serially alternating order.

In some embodiments, the at least two different sorts are a first sort and second sort, and a pill of a first sort is stored after a pill of a second sort in a successive alternating order.

In some embodiments, the package comprises one or more of text, marking, color, shape, symbol, or a combination thereof to direct the patient to successively alternate between the pills.

In some embodiments, the package comprises one or more components having one or more shapes or colors to direct the patient to successively alternate between the pills.

In some embodiments, the package is partitioned to segments and formed such that picking pills within the package is more difficult relative to picking a candidate pill out of a separated segment of the package storing immediate candidate pill, thereby directing the patient on the order of intake.

In some embodiments, the package comprises a structure that obstructs picking a pill from the package before the immediate candidate pill to be taken was picked, thereby directing the patient on the order of intake of the pills.

In some embodiments, the package comprises segments such that picking the immediate candidate pill is preceded by separating the segment of the package storing the immediate candidate pill from the rest of the package.

In some embodiments, the package is at least one of structured or comprises material such that picking the immediate candidate pill initiates at least one of a process or mechanism that allows picking the next candidate pill only after a period of time.

In some embodiments, the period is about the interval between alternating days, thereby compelling the patient to adhere to the alternating days regimen.

In some embodiments, the period is about 24 hours.

In some embodiments, the package about the next candidate pill after the period of time has elapsed is differently marked relative to other parts of the package.

In some embodiments, the package further storing the pills of the at least two different sorts, each compartment storing at least one pill.

In some embodiments, the pills of at least two sorts comprise pills of at least two compositions.

In some embodiments, the at least two different sorts comprise at least one of a medication and at least one of a placebo.

In some embodiments, the at least two different sorts comprise at least one of a statin medication and at least one of an antiplatelet medication.

In some embodiments, the statin medication comprises one of atorvastatin or rosurvastatin.

In some embodiments, the antiplatelet medication comprises one of aspirin or plavix (clopidogrel).

According to an aspect of some embodiments of the present invention there is provided a package storing pills for consumption by a user, the package comprising: (a) a plurality of servings of a first sort, each serving of said first sort comprises at least one pill;

(b) a plurality of servings of a second sort, each serving of said second sort comprises at least one pill wherein said serving of said second sort being different than said serving of said first sort; and

(c) an arrangement for directing the user to successively alternate between consumption of a serving of said first sort and consumption of a serving of said second sort.

In some embodiments, the package is structured to direct the patient to successively alternate between the pills.

In some embodiments, the at least two different compositions comprise at least one of a medication and at least one of a placebo.

In some embodiments, the at least two different compositions comprise at least one of a statin medication and at least one of an antiplatelet medication.

According to an aspect of some embodiments of the present invention there is provided a method for directing a patient to a non-periodic medication regimen, comprising serially providing at least two different sorts of drugs for alternating successive periodic intake.

In some embodiments, at least one sort of drug is provided as a placebo for intake when a medication is not required, thereby marinating a periodic intake by the patient.

In some embodiments, a period is about 24 hours. BRIEF DESCRIPTION OF THE DRAWINGS

Some non-limiting exemplary embodiments of the invention are illustrated in the following drawings.

Identical or duplicate or equivalent or similar structures, elements, or parts that appear in one or more drawings are generally labeled with the same reference numeral, optionally with an additional letter or letters to distinguish between similar objects, and may not be repeatedly labeled and/or described.

Dimensions of components and features shown in the figures are chosen for convenience or clarity of presentation and are not necessarily shown to scale or true perspective. For convenience or clarity, some elements or structures are not shown or shown only partially and/or with different perspective or from different point of views.

Fig. IA schematically illustrates a perspective view of a package (or part thereof) as a strip of a sheet with blisters storing pills as known in the art;

Fig. IB schematically illustrates a top view of a package (or part thereof) as a strip of a sheet with blisters storing pills as known in the art;

Fig. 1C schematically illustrates a side cross-section view of a package (or part thereof) as a strip of a sheet with blisters storing pills as known in the art;

Fig. ID schematically illustrates a top view of a package (or part thereof) as a strip of a sheet with blisters in different shapes storing different pills of respective different shapes as known in the art;

Fig. 2 A schematically illustrates a top view of a set of packages having blisters storing pills and marked for alternating days regimen, according to exemplary embodiments of the invention;

Fig. 2B schematically illustrates a top view of a blisters package storing pills of alternate shapes and marked for alternating days regimen, according to exemplary embodiments of the invention;

Fig. 2C schematically illustrates a top view of a blisters package storing in a staggered ('zigzag') arrangement pills having alternate shapes and marked for alternating days regimen, according to exemplary embodiments of the invention;

Fig. 2D schematically illustrates a top view of a blisters package storing pills having alternate shapes and marked for alternating days regimen where the package structure indicates the intake sequence, according to exemplary embodiments of the invention;

Figs. 2E-F schematically illustrate top views of circular blisters packages storing pills and marked for alternating days regimen, according to exemplary embodiments of the invention;

Figs. 2G-I schematically illustrate top views of blister packages storing single pills and pairs of pills alternatively for alternating days regimen, according to exemplary embodiments of the invention;

Fig. 3A schematically illustrates a side cross-section view of a package (or part thereof) for storing pills, formed as a strip of a sheet with blisters and strengthened about the foil base thereof, according to exemplary embodiments of the invention;

Fig. 3B schematically illustrates a side cross-section view, orthogonal to that of Fig. 3 A, of a package (or part thereof) for storing pills, formed as a strip of a sheet with blisters and strengthened about the foil base thereof, according to exemplary embodiments of the invention;

Fig. 3C schematically illustrates a side cross-section view of a package (or part thereof) derived from Fig. 3A and having a bar anchored at two locations per each segment of the package, according to exemplary embodiments of the invention;

Fig. 3D schematically illustrates a side cross-section view of a package (or part thereof), such as of Fig. 3C, after breaking off a segment of an immediate candidate pill, according to exemplary embodiments of the invention;

Fig. 3E schematically illustrates a side cross-section view of a package (or part thereof), such as of Fig. 3C, after breaking off a segment of an immediate candidate pill in another variation, according to exemplary embodiments of the invention;

Fig. 4A schematically illustrates a side cross-section view of a package (or part thereof) as a derivation from Fig. 3C such as by simplification thereof, with a bar anchored about the indention between segments, according to exemplary embodiments of the invention; and

Fig. 4B schematically illustrates a side cross-section view of a package (or part thereof), such as of Fig. 4A, after breaking off a segment of an immediate candidate pill, according to exemplary embodiments of the invention. DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The following description relates to one or more non-limiting examples of embodiments of the invention. The invention is not limited by the described embodiments or drawings, and may be practiced in various manners or configurations or variations. The terminology used herein should not be understood as limiting unless otherwise specified.

With respect to the accompanying drawings, different shades of gray about a surface of the illustrated packages and of the illustrated pills represent also different colors.

The non-limiting section headings used herein are intended for convenience only and should not be construed as limiting the scope of the invention.

Prior art packages

Fig. IA schematically illustrates a perspective view of a package 100 (or part thereof) as a strip of a sheet 110 with blisters 104 about the top surface 102 thereof storing pills 108 between the blisters and bases 106 of rippable foils, as known in the art.

Fig. IB schematically illustrates a top view of a package 100 (or part thereof) as a strip of a sheet 110 with blisters 104 about the top surface 102 thereof storing pills 108 between the blisters and bases 106 of rippable foils, as known in the art.

Fig. 1C schematically illustrates a side cross-section view of a package 100 (or part thereof) as a strip of a sheet 110 with blisters 104 about the top surface 102 thereof, storing pills 108 between the blisters and bases 106 of rippable foils, as known in the art. The side view is such as cross-section A-A of the package of Fig. 2B. Dashed lines 111 indicate that the package can be extended include more blisters and pills, as shown, for example, in Figs. IA-B.

Fig. ID schematically illustrates a top view of a package 120 as a strip of a sheet with blisters 104 in different shapes about the top surface 102 thereof, storing different pills 112 and 114 of respective different shapes and/or color between the blisters and bases 106 of rippable foils, as known in the art. For example, pills 112 are statins and pills 114 are aspirin as in PRAVIGARD™ PAC. It should be noted that there is no suggestion or implication in package 120 of the order of taking pills 112 and 114. On the contrary, as the pills are disposed as pairs it may be construed that they are taken as pairs of pills 112 and 114.

It should be noted that although drawings and embodiments described herein refer to packages storing pills, the invention also comprises corresponding packages designed or manufactured or produced for storage and use accordingly.

Distinctive blister packages

Fig. 2A schematically illustrates a top view of a set of packages 210 having blisters storing pills and marked by different colors (shown as different shades of gray) for alternating days regimen, each package having blisters 104 about the top surface 102 thereof storing two sorts of alternate pills 112 and 114 between the blisters and bases 106 of rippable foils, according to some embodiments of the invention.

In some embodiments, the different colors are on the top side, or, optionally or additionally, on the bottom side. Optionally, the pills also have different colors, optionally matching the respective color on the package.

In some non-limiting preferred embodiments of the invention, pills 112 and

114 are statins and antiplatelet drugs, particularly atorvastatin or rosurvastatin as the statin drug and aspirin or plavix as the antiplatelet drug.

In some non-limiting preferred embodiments of the invention, pills 112 are one of statins or antiplatelet drugs, and pills 114 are placebo drugs.

In the specifications and claims, unless otherwise specified, statin and antiplatelet drugs exemplify, without limiting, any two (or more) drugs in alternating days regimen, not excluding a placebo drug.

In some embodiments, optionally in addition or as an alternative to the alternating colors, textual marks indicated the drugs, exemplified in Fig. 2A by ¹S' and

¹A' for "statin" and "aspirin", respectively, though other texts or marks may be also or alternatively used.

In some embodiments of the invention, optionally in addition or instead of to the alternating colors and/or markings, indications of the alternating days regimen is presented, such as the monthly day number, exemplified in Fig. 2A by '1', '2', etc. In some preferred non-limiting embodiments of the invention, as exemplified in Fig. 2A, the drugs are stored in a desired and/or required order of intake on alternating days.

The example illustrated in Fig. 2A as a set comprising two packages 210 each having three pills of each drugs represents a set of a plurality of packages 210 as implied by dashed line 224 (or a single package only), each having any practical or convenient number of pills as implied by dashed line 222. For example, four packages

210 each storing eight pills (four statins and four antiplatelet), providing a month consumption (with some spare pills due to irregularity of moths lengths), or, for example, two package each storing fourteen pills for bi-weekly basis of consumption.

As a variant of package 210 and variations thereof, Fig. 2B schematically illustrates a top view of a blisters package 220 storing pills 112 and 114 of alternate shapes and marked for alternating days regimen.

As a variant of packages 210 and/or 220 and variations thereof, Fig. 2C schematically illustrates a top view of a blisters package 230 storing in a staggered ('zigzag') arrangement different sorts of pills 112 and 114 having alternate shapes and marked for alternating days regimen.

As a variant of any one of packages 210-230 or variations and/or combinations thereof, Fig. 2D schematically illustrates a top view of a blisters package 240 storing different sorts of pills 112 and 114 having alternate shapes and marked for alternating days regimen where the package structure indicates the intake sequence, such as by arrow shape.

Figs. 2E-F schematically illustrate top views of circular blisters packages 250 and 260, respectively, as variants of any one of packages 210-240 or variations and/or combinations thereof, storing different sort of pills 112 and 114 and marked for alternating days regimen such as by arrows, according to exemplary embodiments of the invention. Packages 250 and 260 illustrate as example fourteen pills per package

(e.g. bi-weekly based), but other quantities may be used as well, such as sixteen (e.g. two per month), or any practical or convenient number of packages and pills per packages. Packages 250 and 260 are illustrated with pills of similar shape for convenience only.

As variants of Figs 2A-F, Figs. 2G-I schematically illustrate top views of blister packages 270-290, respectively, storing single pills and pairs of pills alternatively for alternating days regimen. Package 270 stores pairs of antiplatelet drugs, 114a and 114b, such as aspirin and plavix, and single statin drug 112, such as atorvastatin or rosurvastatin, while package 280 stores pairs of statin and antiplatelet drugs 112 and 114a, such as rosurvastatin and aspirin, and the single antiplatelet drug 114b such as plavix. While packages 270-280 exemplify storing pairs of pills in a single blister, package 290 exemplifies storing pairs of pills in separate blisters for the same day. Optionally, in some embodiments, single pill 112 in Fig. 2G or 114b in Figs 2H-I is a placebo pill.

As exemplified by packages 250-290 (Figs. 2E-I), packages directing to take alternate pills on alternating days may have various forms and arrangements, and packages 210-290 or any combinations and/or variations thereof are provided as non- limiting examples. Additionally, for simplicity and/or convenience, packages 220-290 (Figs. 2B-I) are illustrated with a reduced amount of indications relative to the example of package 210, yet any one of packages 210-290 represents a package having any plausible variations to direct the patient to alternate between statin and antiplatelet pills successively and consecutively on alternating days, such as in package 210 or others.

With reference to any one of packages 210-290 or variations thereof or resembling packages, in some embodiments of the invention the package is partitioned to segments 226 which can be snapped off, or cut off, from the package. Optionally, segments 226 are delineated or divided, at least partially, by indentation, indicated, for example, by dotted line 228. Optionally, a package comprises an appendage (e.g. 212 in Fig. 2B) at one or two of ends thereof, and optionally, segment adjacent to a package's end is not divided from the appendage by indentation 228. Bending blister packages

In some embodiments of the invention, a package such as one of packages 210-290 or variations and/or combinations thereof, and/or segments 226 thereof, are formed such that in order to readily or handily pick an immediate candidate pill out of the package (e.g. by ripping foil base 106), segment 226 of the immediate candidate pill has to be cut off the package, while to pick other pills within the package is more difficult or less convenient relative to picking a pill out of a separated segment. Consequently, the regimen of alternating days is supported as pills are practically prevented from being picked from the package inconsistently with the regimen order (e.g. randomly).

For example, sheet 110 of the package is flexible such that it bends when trying to push a pill on foil base 106, making it inconvenient of awkward or clumsy, while a separated segment bends much less than the rest of the package. Optionally the part with the last remaining pill also bends, such as by leaving a sufficient appendage for bending.

As another example, sheet 110 of the package is formed with some strain such that it bends or twists when trying to push a pill on foil base 106, making it inconvenient of awkward or clumsy, while a separated segment bends or twists much less than the rest of the package. Optionally the part with the last remaining pill also twist, such as by leaving a sufficient appendage for twisting.

Braced blister packages

In some embodiments of the invention, the foil base of a blister is strengthened or braced such as by a strip or bar or any suitable element, or a plurality and/or combination thereof (hereinafter 'bar'). The bar inhibits or prevents ripping of the foil under a force or pressure typically or usually used to, or sufficient for, ripping a non- strengthened blister foil (hereinafter 'usual force¹). By breaking the segment of the immediate candidate pill, the bar breaks of snaps off to allow ripping of the foil under a usual force. Consequently, the regimen of alternating days is supported as pills are practically prevented from being picked from the package inconsistently with the regimen order.

As a reference model for some further elaborations, Fig. 3A schematically illustrates a side cross-section view of a package 300 (or part thereof) for storing pills 112 and 114, formed as a strip of a sheet 110 with blisters 104 with foil bases 106 as derived from or as a variation of any one of packages 210-220 and/or 240-290 or a variation of combination thereof.

Package 300 is further strengthened by a bar 302 and has indentations indicated by triangles 228 representing a partial cut or perforations. Dashed line 333 indicates that the package represents an extended package that includes more blisters and pills, as shown, for example, in Fig. 2A or Fig. 2D. Segment 226a represents an immediate candidate at the edge of a package (such as segment marked as '1' in Fig. 2A), and segment 226b represents other segments (such as segment marked as '2' in Fig. 2A).

The side view of package 300 represents an internal cross-section such as A-A in Fig. 2 A or Fig. 2D (see Fig. 1C as a further reference) or any such package. Package 300 is illustrated with pills of similar shape for convenience only.

Fig. 3B schematically illustrates a side cross-section view of package 300 orthogonal to the cross-section view of Fig. 3A, such as internal cross-section B-B in Fig. 2D. Optionally, bar 302 represents a plurality of bars 302 disposed parallel to each other. Optionally or additionally, bar 302 is disposed inside foil 106 or sheet 110.

In some embodiments of the invention, bar 302 is connected (e.g. glued or soldered or welded or otherwise fastened) to segment such as segment 226 of package 300 at one or more locations or sites or spots, supporting bar 302 in strengthening or bracing foil base such as 106 against ripping under a usual force (hereinafter 'anchors').

Fig. 3C schematically illustrates a side cross-section view of package 310 (or part thereof) derived from package 300 of Fig. 3A, for storing pills 112 and 114, formed as a strip of a sheet 110 with blisters 104. Package 310 is strengthened about the foil base 106 thereof with bar 302 anchored at two locations 304 for each segment 226 of package 310, one anchor 304a (or 304c) about one end of a segment and one anchor 304b (or 304d) about the indention 228 at the opposite end of the segment. Anchors 304 are illustrated schematically as ovals but may have any form sufficient or adequate to anchor bar 302 and to provide functionality as descried below.

In some embodiments, segment adjacent to an end of package 310 (similar to segments marked ¹T or '6' in package 210 of Fig. 2A) have different number and/or locations of anchors 304. For example, the last remaining segment 226 does not comprise anchor 304 distant from indentation 228 (as can be represented by anchor 304c)

In some embodiments, packages such as package 310 is structured to resists ripping of foil base 106 under usual force because bar 302 is anchored to sheet 110 at two points per a segment 226. Package 310 is also structured such that when segment 226a as an immediate candidate pill 114 at the edge of package 310 is bent and/or twisted and/or turned, segment 226a breaks off about indentation 228a and separates from (snaps off) the rest of package 310. As segment 226a breaks, bar 302 breaks with anchor 304b about indentation 228a and the separated part 302a of bar 302 is now anchored at one location 304a only (cantilever). Pressing with a usual force on blister 104a of immediate candidate pill 114 bends and/or rotates bar part 302a and rips foil base 106 under pill 114 to let pill 114 out. Consequently, the regimen of alternating days is supported as pills are practically prevented from being picked from the package inconsistently with the regimen order.

Accordingly, Fig. 3D schematically illustrates a side cross-section view of package 310 (or part thereof), such as of Fig. 3C, after breaking off segment 226a of immediate candidate pill 114 and pressing blister 104a on pill 114 ripping foil 106.

In some embodiments of the invention, bar 302 is strained (e.g. by twisting) and/or at least partially fractured. Consequently, as segment 226a breaks and separates of package 310, bar 302 breaks with anchor 304b about indentation 228a and the separated part 302a of bar 302 shatters or breaks. Pressing with a usual force on blister 104a of immediate candidate pill 114 bends and/or rotates bar part 302a and rips foil base 106 under pill 114 to let pill 114 out. Consequently, the regimen of alternating days is supported as pills are practically prevented from being picked from the package inconsistently with the regimen order.

Accordingly, Fig. 3E schematically illustrates a side cross-section view of a package 310 (or part thereof), such as of Fig. 3C, after breaking off 226a segment of an immediate candidate pill 114 where separated part of bar 302 shatters or breaks, according to exemplary embodiments of the invention.

Another example of embodiment for supporting the regimen of alternating days is provided by a simplification of package 310 (Fig. 3C) as described below with respect to Figs. 4A-B.

Fig. 4A schematically illustrates a side cross-section view of a package 400 (or part thereof), as a derivation from package 310 (Fig. 3C) such as by simplification, where bar 302 is anchored only about the indentions 228 between segments. Optionally and preferably the immediate pill segment, and optionally the last segment at the opposite end thereof, comprises an additional anchor 304 about the far end thereof away from nearest indentation 228, such as 304a of package 310 (Fig. 3C). As bar 302 is supported at each segment by two anchors, such as 304b and

304d (possibly with the exclusion of immediate candidate segment or the last remaining segment), picking a pill such a 112 out of the middle of the package and disrupt the alternating days regimen is inconvenient and requires a force greater than the usual force.

Assuming segment 226a as the immediate segment of pill 114 (without an extra anchor 304 such as 304a of package 310), breaking segment 226a about indentation 228a enables to rip foil 106 under pill 114, leaving adjacent segment 226b ready for breaking the next time such as next day.

Accordingly, Fig. 4B schematically illustrates a side cross-section view of a package (or part thereof) 400 such as of Fig. 4A, after breaking off segment 226a of an immediate candidate pill 114, according to exemplary embodiments of the invention.

It should be noted that the simplified structure of package 400 relative to package such as package 310 enables, in some embodiments, to rip off foil 106 under the candidate pill 114 while the segment is still intact with package 400 since segment

226 under the candidate pill is anchored only at one location (cantilever). See also, for example, Fig. 3D and respective description.

In case candidate segment 226a comprises an optional extra anchor 304 (such as 304a of package 310), breaking segment 226a would produce a cantilever as shown in Fig. 3D.

In some embodiments of the invention where bar 302 separates or breaks (e.g. Figs. 3E and 4B), bar 302 is sticky and/or stretchable so that bar 302 or fragments thereof are still connected to the separated segment to avoid dispersing the particles.

Delayed-activation blister packages

Referring to Fig. 3C and also to Fig. 3D or Fig. 3E and the corresponding descriptions above, in some embodiments of the invention anchors 304 about indentation 228 (e.g. 304b or 304d, hereinafter 'cut-anchors') comprise or connect to a reservoir of material adapted to soften or partially dissolve bar 302 (hereinafter 'solvent'). Anchors 304 remote from cut-anchors (e.g. 304c) allow the migration of the solvent into bar 302 while cut-anchors 304 block or prevent the migration of the solvent to farther adjoining segments (e.g. as represented by dashed line 333 of possible extension of package 310). In some embodiments, cut-anchors 304 are immersed in or encapsulate an amount of solvent sufficient to soften bar 302 at a segment 226. Optionally or alternatively, cut-anchors 304 connect to a capsule containing an amount of solvent sufficient to soften bar 302 at a segment 226.

In some embodiments, the solvent is adapted to effect bar 302 but to preserve the other constituents of the package, particularly sheet 110 and foil 106. Optionally or alternatively, bar 302 is coated or clad with a material resistant to the solvent.

In some embodiments, bar 302 is made of or comprises porous or fibrous composition that allows the absorption of the solvent, so that the solvent migrate into bar 302 due to factors such as dissipation or diffusion or chemical affinity or capillary effect or any combination of physical or chemical effects.

The solvent and/or composition of bar 302 are adapted to sufficiently affect the strength of bar 302 only after an approximate controlled time, as discussed below.

As a segment of the immediate candidate pill, such as segment 226a, breaks and separates from package 310, the solvent in or connected to cut-anchor 304 such as anchor 304b is released and migrates into the adjacent segment, such as segment 226b. Within an approximate planned or determined period the solvent softens bar 302 at the adjacent segment to a degree that a usual force is sufficient to rips foil 106 and release a pill. The solvent does not leak to a farther segment as the solvent is blocked by a farther cut-anchor 304 such as 304d.

In some embodiments, the period for softening bar 302 at the adjacent segment is about 24 hours, thus the next pill to be taken is practically not available until the next day, thus requiring or compelling the alternating days regimen. In some cases the period may be different, such as when the alternating days are, in fact, every third day so the period may be about 48 hours. Optionally, the period may be less than 24 hours such as about 12 or about 8 or about 6 hours. Optionally or additionally, for alternating days regimen the period may be less than about 24 hours the to allow taking the next pill a bit earlier than a 24 hours period (and similarly for other timings). In some embodiments, different periods are planned according to the drug, allowing non-regular periods, for example, drug-A follows drug-B in about 12 hours, but drug-A follows drug-B in about 6 hours. In some embodiments, in a segment holding the initial immediate candidate pill (e.g. denoted as T or 7' in package 210 in Fig. 2A) bar 302 is missing or already softened to allow picking the immediate candidate pill with a usual force.

In some embodiments of the invention, the solvent 'develops' a latent marking or color in bar 302 and/or sheet 110 and/or foil 106 (without harming sheet 110 and/or foil 106) Thus, bar 302 which has not yet absorbed the solvent sufficiently to allow using a usual force for picking a pill (not yet due) is marked with a color different from a sufficiently softened bar, for example red and green, respectively. Optionally or additionally, other markings such as text or symbols are used to differentiate between a pill which is due and the rest of the pills in the package. Accordingly, the alternate days regimen is indicated and which pill is due.

Ramifications

Although some non-limiting preferred embodiments of the packages described above are directed to pills 112 and 114 as statins (particularly, without limiting, atorvastatin or rosurvastatin) and antiplatelet (particularly, without limiting, aspirin or plavix) drugs, respectively, yet the packages and variations thereof are suitable for other drugs of alternating days regimen.

It should be emphasized that alternating days is not necessarily every other day but can be, for example, every third day and so forth.

Advantages

Possible and plausible advantages of using statins and antiplatelet medication on alternating days - rather than daily intake of both drugs - is reduction in detrimental side effects and optionally reduction of cost to the patient.

General

All trademarks are the property of their respective owners.

The following non-limiting characterizations of terms are applicable in the specifications and claims unless otherwise specified or indicated in or evidently implied by the context, and a term denotes also variations, derivatives, inflections and conjugates thereof.

The terms 'about', 'close', 'approximate', 'practically', 'generally, 'comparable' and 'similar' denote a respective relation or measure or amount or quantity or degree to yield an effect that has no adverse consequence or effect relative to the referenced term or with respect to an embodiment or the scope of the invention.

The terms 'similar', 'resemble', 'like' and the suffix '-like' denote shapes and/or structures and/or operations that look or proceed as, or approximately as, or suggest the referenced object.

The terms 'preferred', 'preferably', 'typical' or 'typically' do not limit the scope of the invention or embodiments thereof.

The terms 'comprises', 'comprising', 'includes', 'including', 'having' denote 'including but not limited to'.

The term 'may' denotes an option which is either or not included and/or used and/or implemented, yet the option comprises a part of the invention.

The terms 'vertical', 'perpendicular', 'parallel', 'opposite' and other angular and geometrical relationships denote also approximate yet functional and/or practical, respective relationships.

Unless the context indicates otherwise, referring to an object in the singular form (e.g. 'a thing" or "the thing") does not preclude the plural form (e.g. "the things").

The present invention has been described using descriptions of embodiments thereof that are provided by way of example and are not intended to limit the scope of the invention or to preclude other embodiments. The described embodiments comprise various features, not all of which are necessarily required in all embodiments of the invention. Some embodiments of the invention utilize only some of the features or possible combinations of the features. Alternatively and additionally, portions of the invention described or depicted as a single unit may reside in two or more separate entities that act in concert or otherwise to perform the described or depicted function. Alternatively and additionally, portions of the invention described or depicted as two or more separate physical entities may be integrated into a single entity to perform the described/depicted function. Variations related to one or more embodiments may be combined in all possible combinations with other embodiments.

Terms in the claims that follow should be interpreted, without limiting, as characterized or described in the specification.

Claims

1. A package for storing pills for dispensing to a patient, comprising at least two compartments for storing pills of at least two different sorts, each compartment for at least one pill,

wherein the package is formed to direct the patient to successively alternate between pills of a different sort.

2. The package according to claim 1, wherein a pill of one sort is stored after a pill of another sort in a serially alternating order.

3. The package according to claim 1, wherein the at least two different sorts are a first sort and second sort, and a pill of a first sort is stored after a pill of a second sort in a successive alternating order.

4. The package according to claim 1, wherein the package comprises one or more of text, marking, color, shape, symbol, or a combination thereof to direct the patient to successively alternate between the pills.

5. The package according to claim 1, wherein the package comprises one or more components having one or more shapes or colors to direct the patient to successively alternate between the pills.

6. The package according to claim 1, wherein the package is partitioned to segments and formed such that picking pills within the package is more difficult relative to picking a candidate pill out of a separated segment of the package storing immediate candidate pill, thereby directing the patient on the order of intake.

7. The package according to claim 1, wherein the package comprises a structure that obstructs picking a pill from the package before the immediate candidate pill to be taken was picked, thereby directing the patient on the order of intake of the pills.

8. The package according to claim 1, wherein the package comprises segments such that picking the immediate candidate pill is preceded by separating the segment of the package storing the immediate candidate pill from the rest of the package.

9. The package according to claim 1, wherein the package is at least one of structured or comprises material such that picking the immediate candidate pill initiates at least one of a process or mechanism that allows picking the next candidate pill only after a period of time.

10. The package according to claim 9, wherein the period is about the interval between alternating days, thereby compelling the patient to adhere to the alternating days regimen.

11. The package according to claim 9, wherein the period is about 24 hours.

12. The package according to claim 9, wherein the package about the next candidate pill after the period of time has elapsed is differently marked relative to other parts of the package.

13. The package according to claim 1, further storing the pills of the at least two different sorts, each compartment storing at least one pill.

14. The package according to claim 13, wherein the pills of at least two sorts comprise pills of at least two compositions.

15. The package according to claim 13, wherein the at least two different sorts comprise at least one of a medication and at least one of a placebo.

16. The package according to claim 13, wherein the at least two different sorts comprise at least one of a statin medication and at least one of an antiplatelet medication.

17. The package according to claim 16, wherein the statin medication comprises one of atorvastatin or rosurvastatin.

18. The package according to claim 16, wherein the antiplatelet medication comprises one of aspirin or plavix (clopidogrel).

19. A package storing pills for consumption by a user, the package comprising:

(a) a plurality of servings of a first sort, each serving of said first sort comprises at least one pill;

20. The package according to claim 19, wherein the package comprises one or more of text, marking, color, shape, symbol, or a combination thereof to direct the patient to successively alternate between the pills.

21. The package according to claim 19, wherein the package comprises one or more components having one or more shapes or colors to direct the patient to successively alternate between the pills.

22. The package according to claim 19, wherein the package is structured to direct the patient to successively alternate between the pills.

23. The package according to claim 19, wherein the at least two different

compositions comprise at least one of a medication and at least one of a placebo.

24. The package according to claim 19, wherein the at least two different

compositions comprise at least one of a statin medication and at least one of an antiplatelet medication.

25. The package according to claim 24, wherein the statin medication comprises one of atorvastatin or rosurvastatin.

26. The package according to claim 24, wherein the antiplatelet medication comprises one of aspirin or plavix (clopidogrel).

27. A method for directing a patient to a non-periodic medication regimen, comprising serially providing at least two different sorts of drugs for alternating successive periodic intake.

28. The method of claim 27, wherein at least one sort of drug is provided as a placebo for intake when a medication is not required, thereby marinating a periodic intake by the patient.

29. The method of claim 27, wherein a period is about 24 hours.