JP2008526639A - Non-tearable child safety blister package - Google Patents

Abstract

A non-tearable child safety blister package (10) and a method utilizing the blister package (10) are disclosed. The package (10) comprises a single blister sheet (12) and a single sheet of lid material (14). The lid sheet (14) is preferably in close contact with the blister sheet (12) in a peelable state, and makes it easy to peel the lid material (14) from the blister sheet (12) (26). It has. These non-contact areas (26) can only be accessed by cutting at least part of the blister package (10).
[Selection] Figure 1

Description

[Cross-reference of related applications]
This application claims the filing date gain of US Provisional Patent Application No. 60 / 644,263, filed Jan. 14, 2005, the disclosure of which is hereby incorporated by reference. Shall be.

  Many people take various types of drugs as part of their daily routine. Some people take several different pharmaceutical dosage forms within a given period. These pharmaceutical dosage forms include pills, capsules, tablets, liquids and the like. Like many industries that sell tangible products, packaging in these areas has challenges. In many cases, the form of product sales is a factor that determines whether or not to purchase a product. This situation is the same in the pharmaceutical field. However, other concerns in the pharmaceutical industry may affect the packaging format.

  One concern with packaging is the nature of the dosage form. For example, some tablets are fragile and are prone to crushing or breaking (using synonyms, and more specifically). Such dosage forms can easily be damaged both during shipping of the package and when the user opens it. Nos. 5,178,878 and 5,223,264, commonly assigned to the assignee of the present application, which are hereby incorporated by reference, are hereby incorporated by reference Disclosed are relatively soft tablets that are susceptible to seed damage. Tablets belonging to such a category tend to have low hardness. An example of such a tablet is a very soft tablet having a hardness of less than about 15 Newtons (N).

  Standard dosage forms are typically packaged in blister sheets consisting of multiple layers of material sheets having pockets, blisters, or walls that contain the dosage form. One type of conventional blister package is a package having a foil layer, but the user of such a package must break the foil by pressing the tablet into the foil layer. An example of such a conventional blister package is disclosed in U.S. Pat. No. 4,158,411 granted to Hall and others. This disclosure is hereby incorporated by reference. This type of package is sufficient to wrap a standard dosage form, but if a fragile dosage form is packaged in such a package, the agent is used when the fragile dosage form is pushed into the foil layer. May cause damage to the shape. These types of packages are also not generally safe for children.

  Another concern regarding the packaging of pharmaceutical dosage forms concerns safety. Packages that cannot be handled by children, i.e., child safety packages, are often highly desired as dosage form packages. Obviously, a major concern when placing drugs in the home is the possibility of the child getting the drug. For example, even if a child ingests a small amount of some drugs, there is a risk of having a harmful effect on the child. For this reason, packages are often rated based on the number of children who were able to get the drug within 5 minutes. An example of a test procedure standard for providing such a rating is described in US Federal Regulations: 16 CFR § 1700.20.

  Accordingly, there is a need for a package for a dosage form that cannot be handled by children and that is configured to prevent damage to the containing dosage form, particularly fragile or friable.

  The present invention relates to a package and, more particularly, to a package including, but not limited to, a package for a fragile pharmaceutical dosage form or tablet, and more particularly, the package of the present invention opens the package. A non-tearable pediatric safety package that requires cutting the package with a scissors to reveal a fold lid for removing the contents.

  The first aspect of the present invention is a non-tearable blister package for pharmaceutical dosage forms that are fragile or difficult to break. The package preferably comprises a single blister sheet that defines a plurality of unit package areas, each unit package area comprising a recess having an upper opening and a flange surrounding the recess. Each recess may contain one or more dosage forms. The package also includes a single sheet of lid material that is in close contact with the flange in a peelable state. The blister sheet and the sheet of lid material define a non-stick area that facilitates peeling of the lid material from the blister sheet. This non-contact area can only be accessed by cutting at least part of the blister package. In a preferred embodiment, the blister package is made of a material that prevents access, especially by being torn or bitten by a child, and is configured to prevent such access. In other embodiments, the blister sheet and / or lid material is provided with a mark indicating that the blister needs to be cut with a scissors or other similar tool.

  In a particularly preferred embodiment, the blister package is designed to reduce breakage of tablets that are contained and fragile or friable. The frangible dosage form disposed in each recess of the blister of the preferred embodiment preferably engages the walls of the recess so that these walls separate the dosage form from the bottom of the recess and the lid material And is held adjacent to each other. Such an aspect prevents the dosage form from moving during transportation and protects the dosage form from damage. The gap between each dosage form and the bottom of the recess in which the dosage form is disposed will alleviate the impact received by the dosage form when the package is dropped. The concave portion of the package and the dosage form disposed in the concave portion can take basically any shape. For example, the dosage form may be a disc tablet, an oval capsule, or a square pill. Similarly, the shape of the concave portion (in the surface portion of the blister sheet) includes a circular shape, an elliptical shape, a polygonal shape, or a star shape.

  Furthermore, the wall portion and the bottom portion of the concave portion may be defined so as to be in the form of a rotating surface formed around a vertical axis perpendicular to the flange surrounding each concave portion. For example, it is desirable to have a cup-like shape with a concave portion. When the dosage form has a disk shape, each dosage form has an edge that contacts the wall of the recess in which the dosage form is placed. The edges and walls preferably define an annular contact area that is coaxial with the vertical axis of the recess. The edge of such a disc-shaped dosage form may comprise a slope that contacts the wall of the recess. This annular contact area can prevent movement of the dosage form within the blister and can prevent damage to the dosage form that accompanies such movement.

  The package in some embodiments of the present invention is rated as a very high level child safety package, commonly referred to in the industry as “F4”, “F3”, “F2”, or “F1”. ing. These designations are given to packages that have passed for specific tests related to how many children can access the dosage form contained within the package within a given time. The number following “F” is usually the number of tablets that affect a child weighing 25 pounds (11.34 kg). For example, one such test is initiated by 50 children guided to access a dosage form contained within a package. Children are given a package without first explaining how to access the dosage form and given 5 minutes as an attempt to access. Appropriate action to be taken to access the dosage form at this point will be indicated to stop the children's actions after 5 minutes. After this, the children are given an additional 5 minutes to handle the package. According to this test, the F1 package is a package that allows less than 5 children to access one pill in 10 minutes. If less than 5 children have access to two pills, the package will be labeled F2. The F3 package would be a package that allows less than 5 children to access 3 pills in 10 minutes. Although the test described above is one well-known test utilized in the packaging industry, it is clear that there are many different tests that can be done to properly rate the package. These tests are generally conducted in accordance with US Federal Regulations: 16 CFR § 1700.00-1700.20.

  Another aspect of the present invention is a method for removing a dosage form from a blister package. The method according to this aspect includes providing a blister package. The blister package is a blister sheet that defines a plurality of unit package areas, each of the unit package areas including a recess having an upper opening, and a flange surrounding the recess, and a state in which the blister sheet can be peeled to the flange A single sheet of lid material in close contact with each other, wherein the blister sheet and the sheet of lid material define a non-stick region that facilitates peeling of the lid material from the blister sheet, and the non-stick region is defined in the blister package. A single sheet of lid material that can only be accessed by cutting at least a portion. The method also includes the step of cutting at least a portion of the blister package to expose at least one of the non-adhered regions and the cover material to expose at least one dosage form disposed in the recess. Peeling at least a portion, and removing at least one dosage form from the recess. In a preferred embodiment, the blister package is made of a material that prevents access, especially by being torn, bitten, ruptured, etc. by a child and is configured to prevent such access. In other embodiments, the blister sheet and / or lid material is provided with a mark that indicates that the blister needs to be cut with a scissors or other similar tool. In a particularly preferred embodiment, the blister package is contained and is designed to reduce breakage of tablets that are fragile or friable.

  Another embodiment of the invention provides another method for removing the dosage form from the blister package. The method according to this embodiment is a step of providing a blister sheet having unit package regions and a lid sheet for sealing those unit package regions, the region comprising a region where the lid material can be peeled and a region where the lid material cannot be peeled. Including a step in which the disabled area surrounds the periphery of the package. The method can also include accessing an area that can be peeled by a cutting instrument such as a scissors.

  A non-tearable child safety blister package 10 according to an embodiment of the present invention is shown in FIGS. The illustrated blister package 10 cannot be torn, so there is a pediatric safety container for tablets that requires cutting certain parts to access the dosage form contained within the package 10. Will be provided. The blister package 10 includes a blister sheet 12 and a lid material sheet 14. The blister package 10 is designed with the intention that the cut is made using a normal scissor or other common cutting tool.

  The overall design of the blister package 10 prevents children and the like from easily accessing harmful dosage forms. In order to reduce the likelihood that the package will be torn, at least one of the blister sheet 12 or the lid sheet 14 will facilitate tearing of notches, cuts, score lines, etc. at its edges (around the package). It does not have a simple structure. Rather, this edge may be thickened or reinforced to make tearing difficult. That is, at least one of the lid material or the blister sheet may be made of a material that is difficult to tear. The thickness of the lid material or blister sheet will also play a role for this purpose. For example, in some preferred embodiments, the blister sheet 12 is provided from Alcan Pharma Center (hereinafter referred to as “Alcan”) in Shelby Bull, Kentucky and has a thickness of about 205 μm. PCS technology and material specification No. It is good to be comprised from the material marketed as 92011 (henceforth "92011 material"). The 92011 material comprises several different individual layers, for example about 60 μm PVC film, about 25 μm polyamide film, about 60 μm aluminum foil, and about 60 μm added PVC film, these films being Preferably at least joined together by a suitable adhesive. On the other hand, the lid material sheet 14 has a PCS technology / material specification No. PCS technology / material specification No. 15144 having a thickness of about 15144 or about 37 μm. 15127 may be configured. These materials are all commercially available from Alcan, and preferably comprise a paper layer, a polyester film having a thickness of about 12 μm, an aluminum foil layer having a thickness of about 25 μm, and a heat seal film. No. With the Alcan adhesive marketed under the name 4516, the so-called “F1” package can be obtained using the structure shown in FIG. 5 and the materials described above. Note that in some preferred embodiments, the package shown in FIG. 5 may have a length of about 100 mm, most preferably 104 mm, and a width of about 60 mm, most preferably 68 mm. However, it should be noted that even a reliable material can be torn if it is thin enough. Also, other materials that are expected to tear may not tear if they have sufficient thickness or are properly reinforced. Furthermore, if one of these two layers is resistant to tearing, the other layer need not be resistant to tearing. The layer preferably prevents both easy finger rupture and tablet extrusion due to breakage, but the layer makes it difficult for adults to cut with normal household scissors or other common cutting tools The upper limit of thickness is usually not important unless it is so thick.

  The non-tearable blister package 10 is formed by a blister sheet 12 and a lid material sheet 14 as shown in FIGS. The blister sheet 12 includes a plurality of unit package regions 16, each unit package region including a recess 18 (shown in FIGS. 1 and 3) and a flange 20 surrounding the recess. The blister sheet 12 includes six package areas 16, but any number of package areas 16 may be included. As shown in FIG. 3, each recess 18 has a size and shape suitable for accommodating the tablet 1, and includes an upper opening 22 and a closed bottom 24. Preferably, the recess according to the present invention is circular and is 1 inch (25.40 mm) or less, preferably 3/4 inch (19.05 mm) or less, more preferably 11/16 inch (17.46 mm) or less. Most preferably, it has a diameter of ½ inch (12.70 mm) or less. Larger recesses are also feasible in practice, but such large recesses can easily be bitten or punctured and broken.

  The blister sheet 12 also has raised areas 26,28. The raised region and / or the non-contact region 26 further includes a raised finger region 30, 32, 34, and the raised region and / or the non-contact region 28 further includes a raised finger region 36, 38, 40. The terms “lift” and “non-stick” are used interchangeably throughout. The raised connection 42 connects the raised areas 26 and 28 to each other, thereby creating a continuous raised area between each raised area and each of the raised areas and the corresponding finger area. In the embodiment shown in FIGS. 1-3, none of the raised areas and / or finger areas extend to the edge of the blister sheet 12. With such a configuration, the blister package 10 that cannot be torn is formed. It is contemplated that the specific dimensions and / or shape of the blister package 10 may be varied in various embodiments. These raised areas will be described in more detail below in connection with the removal of the lid material.

  The lid material sheet 14 covers the recess 18 and is releasably attached to the flange 20. Therefore, the lid material sheet 14 is a single sheet that covers the tablet 1 accommodated in the recess. The lid material sheet 14 is intended to be attached to the flange 20 by using an adhesive, and such an adhesive is, for example, in some embodiments from Alcan no. 4563, or the aforementioned No. It is marketed under the name 4516. However, it is also contemplated that other schemes may be used to attach the lid material sheet 14 to the flange 20, even if the strength of the attachment is changed to determine the difficulty of removing the lid material. It is also intended to be good. The cutting line 44 may be a seamless mark and may be designed to indicate to the user where to cut to obtain the individual lid areas 46. These individual lid areas 46 are configured to correspond to the unit package area 10. Cutting along the cutting line 44 will result in the isolated unit package region 16 being attached thereto and formed with a corresponding lid area 46, as best shown in FIG. The lid material sheet 14 may further include a cutting mark 48 that indicates to the user where and how to cut along with the cutting line 44. These marks may be written instructions or symbols. The lid sheet may also include a peel mark 50 that indicates where and how the lid area 46 is peeled from the corresponding unit package region 16. Finally, the blister package 10 may include a reinforcing region 60 cut into its adjacent edge to increase resistance to tearing. These reinforcing regions 60 may be thick regions, or may be regions where the structure is embossed or bonded.

  As best shown in FIG. 3, by cutting and then separating the individual unit package areas 16 and their corresponding individual lid areas 46, the user can access the aforementioned raised areas. It becomes. Although FIG. 3 shows a raised area 26, it should be noted that any raised area or area can be accessed by separating the other unit package area 16 from the other unit package area 16. . As shown in FIG. 3, the raised region 26 constitutes a non-adhering region between the blister sheet 12 and the lid material sheet 14. Basically, the raised area prevents the cover sheet 14 from being releasably attached to the blister sheet 12 over its entire area, so that the user grabs the cover material and peels it off. It constitutes an area that can be taken. The raised finger areas described above constitute unattached areas added to allow easy removal of the lid material corresponding to different lengths of the unit package area. In order to gain access to these non-adherent areas, the user must cut at least a portion of the blister package 10 because none of the raised areas or raised finger areas extend to the edge of the blister sheet 12. Is no longer.

  The embodiment shown in FIGS. 1 and 2 facilitates access to a dosage form contained in one or more recesses 18 by detaching the individual unit package areas 16 and corresponding lid areas 46 from the blister package 10. It is the composition which can do. That is, the embodiment shown in FIGS. 1 and 2 is configured such that more than one lid area 46 can be easily grasped and peeled off by separating a single unit package area. Yes. However, other embodiments are also conceivable that are configured such that a single lid area can be peeled from its corresponding unit package area only by removing one unit package area. For example, in the structure shown in FIG. 4, a blister package 110 having a configuration different from that of the blister package 10 is provided. The blister package 110 may include a blister sheet configured in the same manner as the blister package 10. However, in what is shown in FIG. 4, the lid sheet 114 is provided with cutting lines 144 that are arranged differently, thereby forming lid areas 146 that are arranged differently. The lid sheet 114 may include a cutting mark 148 and a peeling mark 150 as with the blister sheet 14.

  The cutting line 144 is arranged such that the lid area 146 corresponding to that particular unit package area can be peeled off only by cutting a single unit package area. As shown in FIG. 4, the remaining area 152 is left by separating the individual unit package areas. In some embodiments, these remaining areas 152 extend around the raised fingers of the blister sheet 12. This prevents the other lid area 146 from being peeled off. This is because, after separating the unit package area, the user can access only a part of the raised area, but cannot access the raised fingers. On the other hand, it is contemplated that in other embodiments, it may be possible to provide a blister sheet configured to allow access to both the raised and finger areas when removing the lid area 146. ing. Basically, these blister sheets are configured to fit the lid sheet 114.

  The design of the blister package 10 is a recess that works in conjunction with such a dosage form to prevent the fragile dosage form from moving during transport and / or to mitigate the impact received by the fall of the package. By providing 18, it is intended to be able to protect fragile dosage forms. US Pat. No. 6,155,423 (the '423 patent) to Katzner et al., Commonly assigned to the assignee of the present application, suggests one solution to this problem. Yes. This disclosure is hereby incorporated by reference. The '423 patent discloses a blister package having a peelable layer. If this peelable layer is peeled off, the dosage form will be accessible. Thus, in the '423 patent, the user can easily access such a dosage form without damaging the fragile dosage form. The blister package of the '423 patent is also designed to promote tablet protection during storage, shipping, and use. The present invention can utilize a similar design.

  In some embodiments of the present invention, a fragile dosage form is disposed in each recess 18 of the blister sheet 12, wherein the dosage form is engaged with the wall of each recess 18, Holds the dosage form adjacent to the lid material 14 while being separated from the closed bottom 24 of the recess 18. Such an arrangement is best shown in FIG. By this aspect, the dosage form is protected to prevent movement during transport and to prevent damage. The gap between each dosage form and the closed bottom 24 of the recess 18 in which the dosage form is placed mitigates the impact applied to the dosage form when the package 10 falls or otherwise receives vibration. Will be. The recess 18 and the corresponding dosage form disposed in the recess 18 can take essentially any shape. For example, the dosage form may be a disc tablet, an oval capsule, or a square pill. Similarly, the shape of the recess 18 (in the surface portion of the blister sheet) includes a circular shape, an elliptical shape, a polygonal shape, or a star shape.

  In addition, the wall of the recess 18 and the closed bottom 24 can be defined to be in the form of a rotational surface formed about a vertical axis perpendicular to the flange 29 surrounding each recess 18. For example, the recess 18 may have a curved cup shape. When a dosage form is a disk shape, those dosage forms are good to have an edge part which contacts the wall part of the recessed part 18 in which a dosage form is arrange | positioned, respectively. The edges and walls define an annular contact area that is coaxial with the vertical axis of the recess 18. The edge of such a disk-shaped dosage form may be a slope that contacts the wall of the recess 18. The annular contact area prevents movement of the dosage form within the blister and prevents damage to the dosage form that accompanies such movement.

  The tablet package according to the present invention is designed to keep children safe. This package is rated as a package having a very high safety level for children or higher. In fact, the tablet package 10 is designed to prevent a relatively large number of children from accessing the drug within a predetermined time. Some embodiments according to the present invention are rated at a high enough level to be rated in the well-known industry standard known as the F1 package as described above. Other embodiments are rated F2 or F3. Accordingly, various embodiments are contemplated that accommodate various types of dosage forms. Although the present invention has been described with respect to fragile or friable dosage forms, it is contemplated that other types of dosage forms may be accommodated. However, it should be noted that the user should select the appropriate package for a particular subject. For example, a harmful dosage form should be packaged at a very high pediatric safety level, while a low-risk dosage form may be packaged at a low pediatric safety level.

  Finally, one preferred method of forming the blister packages 10, 110 described above and a preferred process for packaging the dosage form 1 in these packages 10, 110 will be described. It should be understood that many different suitable processes may be utilized by the present invention, and the method described below is only one preferred method. In such a method / process, the material sheet forming the blister sheet 12 and the lid material 14 is preferably prepared in a roll and then fed or loaded into a blister machine. Note that such machines are well known in the art. The material forming the blister sheet 12 is then preferably moved to a forming station where the recesses 18 are formed in the material by a tool such as a forming plug. The tablet 1 is then preferably placed in each open recess 18 of the blister sheet 12.

  With each of the recesses 18 containing one or more tablets 1, the blister sheet 12 is preferably moved to a sealing station where the lid material 14 is transferred to the blister sheet 12 using upper and lower sealing plates. Close contact with. The sealing plate described above preferably heats the adhesive (as described above) by the action of heat and pressure over the course of a specific residence time (cycle / speed), so that the lid material 14 is applied to the blister sheet 12. In close contact. Following this sealing step, the desired perforations are formed in the package and the individual blister cards 10 (with a number of recesses 18) are stamped. It should be noted that the perforations formed will have an advantageous effect in this punching procedure, but will remain in the final blister package 10 as described above. Finally, the individual packages 10 are fed to the final packaging station, preferably via a conveyor or the like.

  The dosage form in the form of a normal tablet that can be packaged using the present invention is not limited by the type of tablet or type of active pharmaceutical ingredient (API) used herein. Examples of these APIs include, but are not limited to, analgesics, anti-inflammatory drugs, antipyretic drugs, antibiotics, antibacterial drugs, anti-anxiety drugs, laxatives, appetite suppressants, antihistamines, antidepressants, antiasthmatic drugs, anti Diuretic, Intestinal, Antimigraine, Anticonvulsant, Analgesic, Anti-Hyperactive, Antihypertensive, Tranquilizer, Decongestant, Beta inhibitor, Peptide, Protein, Oligonucleotide, and Biological origin Other materials, as well as combinations thereof. Also conceivable are the drugs and active pharmaceutical ingredients described in columns 18-21 of US Pat. No. 5,234,957 assigned to Mantelre. The text of this Mantel patent is hereby incorporated by reference. Any of the APIs described above may be used in the form of any salt, hydrate, solvate, polymorph, or individual optical isomer, and mixtures thereof.

  Specifically preferred are opiates, drugs used to treat pain, drugs used in psychiatry such as clozapine or used to treat schizophrenia, and cytotoxic substances. Also, any API that is intended for the treatment of the elderly or a safety package for children, more specifically any API that requires the use of the “F1” package is preferred.

  Examples of legal opiates that can be packaged according to the present invention include, but are not limited to, alfentanil, alpha-prozin, anilellidine, benzylmorphine, vegitramide, buprenorphine, butorphanol, clonitazene, codeine, codeine phosphate, desomorphine, dextromolamide , Dezocine, Diampromide, Dihydrocodeine, Dihydrocodeinone Enol Acetate, Dihydromorphine, Dimenoxadol, Dimefeptanol, Dimethylthiambutene, Dioxafetil Butyrate, Dipipanone, Epazosin, Ethoheptadine, Ethylmethylthiambutene, Ethylmorphine , Etonitazen, fentanyl, hydrocodone, hydromorphine, hydroxypetidin, isomethadone, ketobemidone, levorphanol, lofe Tanyl, meperidine, meptazinol, metazocine, methadone, methopone, morphine, morphine hydrochloride, morphine sulfate, mylofin, nalbuphine, narcein, nicomorphine, norlevorphanol, normethadone, normorphine, norpipanone, opium, oxycodone, oxymorphone, papberetam, pentazocine, phenazosin, phenazosin , Prescription drugs such as phenazosin, phenoperidine, pimidine, pyritramide, proheptadine, promedol, propylme, propoxyphene, remifentanil, sufentanil, and thyridine. The class of compounds commonly known as opiates also includes illegal drugs such as heroin and cocaine. Opiates according to the present invention include those mentioned above and those listed as controlled substances in accordance with US Federal Regulations: 21 CFR §1308.12. Opiates are being administered to patients to relieve various types of pain, most often for a variety of reasons.

  Cytotoxic substances include any agent that kills cells. These substances are generally used for the treatment of malignant diseases and other diseases. These substances are intended to destroy rapidly growing cancer cells. These substances have been found to exhibit mutagenicity, carcinogenicity, and / or teratogenicity either in therapeutic dosing or animal studies and bacterial analysis. Cytotoxic drugs that interfere with important cellular processes, such as DNA, RNA, and protein synthesis, have been conjugated to antibodies before being used for in vivo therapy. Examples of such drugs include, but are not limited to, the following drugs.

  i) intercalating agents, in particular doxorubicin (adriamycin), daunorubicin, epirubicin, idarubicin, zorubicin, aclarubicin, pirarubicin, acridine, mitoxantrone, actinomycin D, eptoirinium acetate;

  ii) alkylating agents selected from platinum derivatives (cisplatin, carboplatin, oxaliplatin);

  iii) cyclophosphamide, ifosfamide, chlormethrin, melphalan, chlorambucil, estramustine, busulfan, mitomycin C, nitrosourea: BCNU (carmustine), CCNU (lomustine), fotemustine, streptozotocin, triazine or derivatives: procarbazine, dacarbazine, A compound selected from the other group of alkylating agents consisting of pipbloman, ethyleneimine: artretamine, triethylene-thio-phosphoramide;

  iv) Folic acid antimetabolite: methotrexate, raltitrex, pyrimidine antimetabolite: 5-fluorouracil (5-FU), cytarabine (Ara-C), hydroxyurea / purine antimetabolite: linetole, thioguanine, pentostatin , Cladribine, cytotoxic nucleoside synthesis inducer: a compound selected from another group of antimetabolite drugs consisting of gemcitabine;

  v) Tubulin affinity agent, vinca alkaloid that disrupts the spindle: vincristine, vinblastine, vindesine, navelbine, an agent that prevents depolymerization of the spindle: induces DNA cleavage by preventing paclitaxel, docetaxel, topoisomerase II Agent: etoposide, teniposide, topoisomerase I inhibitor that induces DNA cleavage: compound selected from the other group consisting of topotecan, irinotecan;

  vii) a DNA separating or disrupting agent such as bleomycin;

  viii) Compound: one of pricamycin, L-asparaginase, mitoguazone, dacarbazine;

  viii) anticancer progesterone steroids: medroxyprogesterone, megestrol

  ix) anticancer estrogenic steroids: diethylstilbestrol; phosfestol tetrasodium;

  x) antiestrogens: tamoxifen, droloxifene, raloxifene, aminoglutethimide; and

  xi) Steroidal antiandrogens (eg cyproterone) or nonsteroidal antiandrogens (flutamide, nilutamide).

In addition to the APIs described herein, the dosage forms of the present invention can additionally or alternatively include vitamins, minerals, and dietary supplements. As used in this disclosure, the term “vitamin” refers to trace amounts of organic substances required in a diet. In the present invention, the term “vitamin” is not limited, but includes thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B ₁₂ , lipoic acid, ascorbic acid, vitamin A, vitamin D, Contains vitamin E and vitamin K. The term “vitamin” includes vitamin coenzymes. Coenzymes are specific chemical forms of vitamins. Examples of coenzymes include thiamine pyrophosphate (TPP), flavin mononucleotide (FMM), flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADP), complement enzyme A (CoA), pyridoxal phosphate, biocytin, tetrahydrofolic acid, coenzyme B _12, lipoyllysine, 11-cis - retinal and 1,25-dihydroxy cholecalciferol beam and the like. The term “vitamin” also includes choline, carnitine, and α, β, and γ carotene.

  The term “mineral” refers to an inorganic substance, a metal or the like necessary for a human diet. Thus, the term “mineral” as used herein includes, but is not limited to calcium, (calcium carbonate), iron, zinc, cerium, copper, iodine, magnesium, phosphorus, chromium, and the like, and mixtures thereof. include. As used herein, the term “nutritional supplement” means a substance that exhibits an adequate nutritional effect when administered in small amounts. Examples of dietary supplements include, but are not limited to, materials such as pollen, bran, wheat germ, kelp, cold liver oil, ginseng, and fish oil, amino acids, proteins, and mixtures thereof. If well understood, dietary supplements may contain vitamins and minerals.

  In general, the amount of active ingredient contained in each tablet or dosage form (API, vitamins, minerals, dietary supplements, etc.) may be selected according to well-known principles of pharmacy. The effective amount of API has been specifically studied. It is to be understood that the term “effective amount” is considered based on, for example, “pharmaceutically effective amount”. A “pharmaceutically effective amount” is an amount of a drug or API sufficient to obtain a required or desired therapeutic effect, ie, sufficient to obtain an appropriate biological effect when taken by a patient. Amount. The term “effective amount” as used with respect to vitamins or minerals means an amount of at least about 10% of the US recommended daily intake (RDA) of a particular ingredient required by the patient. For example, if the desired ingredient is vitamin C, an effective amount of vitamin C will be an amount of vitamin C sufficient to provide 10% or more of the RDA. Typically, if the tablet contains minerals or vitamins, it will contain large amounts, preferably about 100% or more of the applied RDA.

  The amount of active ingredient used can vary greatly. Of course, the size of the dosage form, the requirements of the other ingredients, and the number of tablets administered at one time, for example the number of tablets, will all affect the upper limit of the amount of pharmacologically active ingredient used. Generally, however, the active ingredient is included in an amount greater than 0 to about 80% by weight of the final tablet, more preferably from greater than 0 to about 60% by weight of the final tablet. ing. That is, the active ingredient is contained within a range of about 1 μg to about 2 g, more preferably about 0.01 g to about 1000 g per dosage form, ie, per tablet.

  Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. Accordingly, many modifications may be made to the exemplary embodiments and other arrangements devised without departing from the spirit and scope of the invention as defined in the claims. It should be understood that

  The present invention has broad industrial applicability including, but not limited to, pharmaceutical packages, particularly in the form of tablets, and even in the form of fragile tablets.

It is a bottom view of the blister package by this invention. It is a top view of the blister package of FIG. It is a sectional side view in the unit package area | region of a blister package along line AA of FIG. FIG. 6 is a top view of a blister package according to another embodiment of the present invention. FIG. 10 is a bottom view of a blister package according to still another embodiment of the present invention.

Claims (17)

In a blister package that cannot be torn,
A single blister sheet defining a plurality of unit package areas, each unit package area comprising a recess having an upper opening and a flange surrounding the recess;
A single sheet of lid material that adheres to the flange in a peelable state, wherein the blister sheet and the lid material sheet define an unadhered region that facilitates peeling of the lid material from the blister sheet A single sheet of lid material that allows the unbonded area to be accessed only by cutting at least a portion of the blister package;
A blister package characterized by comprising:   The blister package according to claim 1, further comprising a mark for instructing cutting of the blister package.   The blister package according to claim 1, wherein the blister sheet includes six unit package regions.   The blister package according to claim 3, wherein at least two cuts must be made in order to access all of the non-contact areas.   The blister package according to claim 1, wherein the concave portion includes a wall portion and a closed bottom portion.   A dosage form is disposed within the recess and engages the wall portion of the recess so that the wall portion is spaced from the closed bottom and adjacent to the lid material. The blister package according to claim 5, wherein a gap is generated between the dosage form and the closed bottom of the recess.   A packaged formulation comprising the package of claim 1 and a plurality of pharmaceutical dosage forms disposed within the recess.   8. The packaged preparation according to claim 7, wherein the pharmaceutical dosage form is fentanyl. In the method of taking a fragile dosage form from a blister package,
Providing a blister package, wherein the blister package is a blister sheet defining a plurality of unit package areas, each of the unit package areas having a recess having an upper opening and a flange surrounding the recess; A single blister sheet provided and a single sheet of lid material that is in close contact with the flange in a peelable state, the blister sheet and the lid material sheet easily peeling the lid material from the blister sheet Defining a non-adherent region, wherein the non-adherent region is accessible only by cutting at least a portion of the blister package; and
Cutting at least a portion of the blister package to expose at least one of the non-stick regions;
Peeling at least a portion of the lid material to expose at least one dosage form disposed within the recess;
Removing the at least one dosage form from the recess;
A method comprising the steps of:   The method of claim 9, wherein the step for cutting includes performing the cutting a number of times.   The method of claim 10, wherein the step for cutting comprises separating at least one unit package region from other unit package regions.   The method of claim 9, wherein the step for cutting includes exposing a number of unattached areas.   The method of claim 9, wherein the step for stripping comprises stripping an area of the lid material corresponding to the unit package area. In a method of removing a dosage form from a blister package,
A step of providing a blister sheet having a unit package region, and a lid sheet for sealing the unit package region, the region comprising the region where the lid sheet is peelable and the region where separation is impossible, and the region where separation is impossible Surrounding the periphery of the package;
Accessing the peelable region with a cutting instrument;
A method comprising the steps of:   The method of claim 14, further comprising peeling the lid material.   The method of claim 15, further comprising removing the dosage form.   The method of claim 14, wherein the cutting instrument is a scissors.

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