Methods for searching for possible forms of a sample and methods of screening a sample according to its form comprise disposing the sample in at least one receptacle that defines a capillary space, such as a capillary tube. The sample is solidified to generate at least one solid form or semisolid form, and the generated form is analyzed and classified. The analysis may determine differences in molecular arrangement of the various forms or characteristics that reflect the form. The methods may employ a plurality of samples, conditions, or receptacles in an effort to generate a variety of forms, so that all or a high percentage of possible forms are obtained.

The present methods relate to screening for possible solid forms of a sample and include solidifying the sample in at least on receptacle defining a capillary space, such as a capillary tube of well plate. The present methods also relate to screening a sample according to its solid forms and include solidifying the sample in a plurality of receptables and at least one receptacle defines a capillary space. The solid for of the sample refers to its arrangement at the molecular or atomic level in the solid. The solid forms generated by the solidification step are analyzed and classified, such as by x-ray diffraction patterns. The present methods increase the likelihood of generating all or a high percentage of possible solid forms.
In the chemical field, the unpredictability and variability of compounds, mixtures, and processes are well established. Certain chemical compounds or mixtures may have utility for numerous different applications, including vital biological applications, yet a slight change in those compounds or mixtures, even with respect to a single atom, may reduce or eliminate their utility for their beneficial purpose. Similarly, certain chemical processes may have significantly better or worse performance based upon seemingly minor differences.
In the pharmaceutical field, a great deal of time, effort and expense is spent on the identification of particular compounds and mixtures that will have beneficial effect. Furthermore, exhaustive research must be done as to whether such compounds and mixtures will have harmful effects. Once again, even slight differences in chemical composition or structure may yield significant differences in biological activity. Thus, researchers frequently test many different compounds and mixtures for biological activity and other effects as well as testing different processes and conditions for the preparation of such chemical compounds and mixtures.
The process of thorough analysis of different chemical compounds, elements, mixtures, processes, or structures is commonly referred to as screening. Screening may be a function of time and effort, with the quality or results of screening being a function of the number of samples prepared and/or analyzed as well as the quality of preparation and/or analysis underlying those samples. Screening plays a vital role in the pharmaceutical field, as the most advantageous formulation of a biologically active compound or mixture is frequently found through successful screening processes.
However, screening processes can require significant amounts of time, effort and resources. There is a continuous need for improved screening processes having increased reliability and efficiency.
Processes have been used for screening chemical compounds according to their form. When a compound has different solid or crystalline forms, the different forms are frequently referred to as polymorphs of the compound. A xe2x80x9cpolymorphicxe2x80x9d compound as used herein means a compound having more than one solid form. For example, a polymorphic compound may have different forms of its crystalline structure, or different forms based upon hydration, or it may have a crystalline form and an amorphous form. In the past, screening processes have not identified with sufficient consistency and reliability a high percentage of possible solid and semisolid forms.
The form of a compound or mixture may have an impact on biological activity. The same chemical compound may exhibit different properties depending upon which form (such as amorphous or crystalline or semisolid) that compound is in. A xe2x80x9csemisolidxe2x80x9d form is used herein to indicate materials like waxes, suspensions, gels, creams, and ointments. The term xe2x80x9csolid formxe2x80x9d herein includes semisolid forms. Furthermore, a chemical compound may exist in different solid forms, and those different solid forms may also exhibit different properties. As a result, different solid forms, including different crystalline forms, of a chemical compound may have greater or lesser efficacy for a particular application. The identification of an optimal solid form is important in the pharmaceutical field, as well as in other fields including nutraceuticals, agricultural chemicals, dyes, explosives, polymer additives, lubricant additives, photographic chemicals, and structural and electronic materials. The new methods described herein may be useful in any of these fields as well as others where solid materials are used.
A chemical compound or mixture may be amorphous, meaning that it is not characterized by a regular arrangement of molecules. Alternatively (or even to a limited extent within a mostly amorphous form), a compound or mixture may be arranged in a crystalline state, where the molecules exist in fixed conformations and are arranged in a regular way. The same compound or mixture may exhibit different properties depending upon which solid form that compound or mixture is in.
It is important in the pharmaceutical field as well as other fields to find the form of a chemical compound that exhibits appropriate physical and chemical properties. One form may be more stable or have other properties that make it preferable over other forms. One form of a chemical composition may have better bioavailabilty, solubility, or adsorption characteristics or in other ways be more suitable for delivery of therapeutic doses than other forms. As part of a screening method, it may be advisable to evaluate different salts of a chemical compound (or more precisely, different salt compounds of a given biologically active ion). It is frequently desirable within a screening process to generate, or at least search for, a high percentage of the possible solid forms of a compound or mixture. Past attempts to generate a variety of solid forms involved flash evaporations, cooling under different conditions and/or the addition of seeds of solid material. However, some materials strongly resist the generation of new solid forms.
One or more solid forms may be generated by crystallization of the sample. Among the phenomena in crystallization are nucleation and growth. Crystal nucleation is the formation of an ordered solid phase from liquids, supersaturated solutions, saturated vapors, or amorphous phases.
Nucleation may be achieved by homogeneous or heterogeneous mechanisms. In heterogeneous mechanisms, some solid particle is present to provide a catalytic effect and reduce the energy barrier to formation of a new phase. Crystals may originate on a minute trace of a foreign substance (either impurities or container walls) acting as a nucleation site. Since nucleation may set the character of the crystallization process, the identity of the foreign substance is an important parameter. The presence of xe2x80x9cseedsxe2x80x9d of other crystalline compounds in a crystallization environment can be beneficial, detrimental, or both, but in any event, must be considered. Growth is the enlargement of crystals caused by deposition of molecules on an existing surface. In homogeneous mechanisms, it has been theorized by others that nucleation is achieved spontaneously with the solution comprising the solute to be crystallized in solvent typically by evaporation, temperature reduction, or addition of antisolvent.
Typically, a solid to be crystallized is present in a solution at, above, or below its saturation point at a given temperature. Crystallization is initiated or facilitated by removing solvent, changing temperature, and/or adding an antisolvent. The solvent may be removed by evaporation or other means. Eventually the solution reaches a point where crystals will grow.
A specific chemical substance may crystallize into different forms or transition from one polymorph form, pseudopolymorph form, or amorphous form to another form. This crystallization into a different form or transition into a different form may be accompanied by other physical or chemical changes. For example, novobiocin has at least two different forms: an amorphous form and a crystalline form. Dog plasma levels of novobiocin vary depending on which form of novobiocin is administered. In one study, two hours after the amorphous form of the drug was administered, the concentration of novobiocin was 29.3 mg/mL. In contrast, when crystalline novobiocin was administered, there was no drug detectable in the dog plasma two hours after the drug was administered. In another example, furosemide has two different crystalline forms, and furosemide solubility in aqueous buffer at pH 3.2 varied depending on which polymorph was studied. After three hours, Form I and Form II had solubilities of approximately 0.025 mg/mL. Under the same conditions and dissolution time, the DMF and dioxane solvates of furosemide had solubilities of approximately 0.035, and Form III had a solubility of approximately 0.045 g/mL.
It is known to generate crystalline samples in capillary tubes. For example, U.S. Pat. No. 5,997,636 discusses a method for growing crystals within a capillary tube. As another example, D. Amaro-Gonzxc3xa1lez et al., xe2x80x9cGas Antisolvent Crystallization Of Organic Salts From Aqueous Solutionxe2x80x9d, Journal Of Supercritical Fluids, 17 (2000) 249-258, discloses results of crystallization of lobenzarit, including crystallizations in capillaries. Lobenzarit is an anti-arthritic agent. Amaro-Gonzxc3xa1lez et al. state that particle size and agglomeration varied depending on the size of the capillary, that it is shown that the size distribution and particle shape can be controlled using different capillary diameters, and that it is possible to obtain individual crystals without agglomeration.
Neither reference discloses that different forms (meaning different arrangements on the molecular or atomic level) were produced, nor does either reference suggest a new method for searching for possible forms or screening a sample according to its form. A different particle size or shape does not necessarily mean there is a different crystal form since a solid form can crystallize into many different shapes. For example, snowflakes may comprise a single crystal form having many different crystal shapes.
It is also known to subject samples within capillary tubes to various spectroscopic analyses, including diffraction analysis such as x-ray diffraction analysis. However, in such instances, it has been the common practice to prepare a solid sample outside the capillary tube before it is placed in the capillary tube for analysis.
There are several factors that discourage the use of capillary tubes for solidifying compounds or mixtures. One factor is that capillary tubes are more difficult to work with than other containers. Another factor is that there has been no general recognition that the use of capillary spaces may affect reactions or lead to compositional or chemical differences. Thus, since it was believed that the same forms and reactions could be done in other containers, it is believed that capillary tubes have not been used as an integral part of a screening process or to search for and generate solid and semisolid forms.
There is a need for improved screening methods that identify all or a high percentage of possible forms of a compound or mixture. There is a need for improved methods of searching for the possible forms of a sample.
As one aspect, an improved method of searching for possible forms of a sample is provided. The method comprises the steps of disposing the sample on one or more receptacles, where at least one of the receptacles defines a capillary space, and the sample is disposed within the capillary space. The method next comprises solidifying the sample in or on the receptacles to generate at least one form, wherein the generated form(s) is a solid or semisolid. The form(s) is then analyzed and classified, such as by classification according to what form it is.
As another aspect, an improved method of screening a sample according to its form is provided. This method is especially useful for screening a sample comprising a compound or a. mixture having biological activity in at least one form of the compound or mixture. The screening method comprises the steps of disposing the sample on a plurality of receptacles, where at least one of the receptacles defines a capillary space, and the sample is disposed within the capillary space. The method next comprises solidifying the sample in or on the receptacles to generate at least one form, wherein at least one form is a solid or semisolid. The method further comprises analyzing at least one form in a manner wherein the analytical result is indicative of the generated form(s), and classifying the generated form(s), such as by form type or according to analytical result.
The screening method may be particularly useful where the compound or mixture has at least one form having biological application and it is desirable to determine if other forms are possible. The present methods may comprise generating at least one other form of the compound or mixture.
The sample may comprise a known polymorphic compound or comprise at least one material that is not recognized as a polymorphic compound. The sample may consist essentially of a solution of one compound, or may comprise a mixture of compounds.
Preferably, the present methods include disposing the sample on a plurality of receptacles, including at least two different types of receptacles. For example, one portion of a sample may be disposed in a capillary tube that defines a capillary space and another portion of the sample may be disposed on a glass slide that does not define a capillary space. The sample may be prepared in a single batch or in multiple batches. After the portions have solidified, the form disposed in the capillary tube and the form disposed on the slide may be analyzed, classified and compared.
A preferred receptacle defining a capillary space is a capillary tube, and others include a well plate, a block and a sheet with holes or pores of appropriate size and shape.
The present methods may further comprise the step of comparing the generated form to a known form. In many cases, the generating step may produce at least one different form of the sample.
At least some of the receptacles may be subjected to substantially constant motion during the generating step. For example, a capillary tube may be rotated along its longitudinal axis during the generating step or subjected to centrifuging during the generating step. Centrifuging can be sufficient to concentrate the solid or semisolid at one end of a capillary tube and to facilitate in-situ analysis of the generated forms. Also, variations in centrifuging may provide environmental variation, which is desired in a screening method. Centrifuging may move the sample to the bottom of the receptacle when one end of the receptacle is closed. Centrifuging may be performed at a pressure lower than ambient pressure, or under vacuum.
In the present methods, the sample may comprise a compound comprising a biologically active ion or one or more different salts of the compound. A second analyzing step may be performed on generated forms, where the second analyzing step provides data indicative of biological activity or bioavailability.
In the present methods, the generated forms may be analyzed by any suitable means, such as methods selected from the group consisting of visual analysis, microscopic analysis, thermal analysis, diffraction analysis, and spectroscopic analysis. Preferred methods of analysis include Raman spectroscopic analysis and x-ray diffraction analysis, more preferably using synchrotron radiation as the radiation source for the analysis. The analysis may determine differences in arrangement of molecules in the solid or determine one or more other characteristics that directly or indirectly reflect the form.
In the present methods, the step of analyzing the generated form may comprise analyzing the form without removing it from the receptacle in which it was generated. Thus, the present methods are useful for in situ analysis of generated forms. The use of capillary tubes as receptacles can facilitate such in situ analysis.
It may be advantageous to place the sample in at least five receptacles defining capillary spaces, alternatively at least 100 receptacles defining capillary spaces. In some embodiments, a sample is placed in several sets of numerous capillary tubes (for example, from 5 to 2000 capillary tubes, alternatively 5 to 100 capillary tubes), and the different sets are subjected to different methods or conditions of solidification.
The solidifying step may comprise crystallizing the sample, or may be selected from the group consisting of solvent evaporation, cooling, anti-solvent addition, gel diffusion, and thin-layer deposition.
A supersaturated solution of the sample can be formed before, during, or after the sample is disposed on the receptacle(s).
The generating step preferably comprises crystallizing the sample, or alternatively is selected from the group of methods consisting of solvent evaporation, cooling, anti-solvent addition, gel diffusion, and thin-layer deposition (with or without subsequent measures to quickly remove residual solvent, including air of various temperatures forced through the capillaries).
The receptacle that defines a capillary space can be a capillary tube or appropriately sized multi-well plate. Alternatively, the receptacle that defines a capillary space may be a block or a sheet made of polymer, glass, or other material, which has holes or pores of a suitable shape and dimensions. Alternatively, some receptacles need not define a capillary space; indeed, it is considered preferable to employ different kinds of receptacles for generating solid and/or semisolid forms of a given sample. Additional receptacles may include a glass slide or a conveyer surface in addition to the receptacle(s) defining capillary spaces.
The use of receptacles that define capillary spaces is an improvement over more labor-intensive methods of generating solid forms and enables one to obtain a high percentage of possible solid and semisolid forms. Another advantage of such receptacles is that smaller amounts of the compound or mixture are used. A compound is a substance composed of atoms or ions in chemical combination. A compound usually is composed of two or more elements, though as used in accordance with the present methods, a compound may be composed of one element.
A xe2x80x9cpolymorphxe2x80x9d as used herein means a compound or mixture having more than one solid or semisolid form. The xe2x80x9cformxe2x80x9d of a compound or mixture refers to the arrangement of molecules in the solid. A xe2x80x9csemisolidxe2x80x9d form is used herein to indicate materials like waxes, suspensions, gels, creams, and ointments. The term xe2x80x9csolid formxe2x80x9d herein includes semisolid forms. xe2x80x9cCapillary spacexe2x80x9d is defined herein to mean a space having walls separated by from about 0.1 mm to about 30 mm, preferably from about 0.5 mm to about 5 mm, more preferably from about 0.5 mm to about 2.5 mm, in at least one dimension. A capillary tube having an inner diameter from about 0.5 mm to about 2.5 mm , is a preferred receptacle that defines a capillary space in the interior of the capillary tube. It is preferred that the capillary tubes are circular in their interior shapes.
As used herein, the generation of solid and semisolid forms includes any suitable technique for solidification including but not limited to crystallization. Indeed, the forms which may be sought or generated may include amorphous forms, mixtures of amorphous forms, eutectic mixtures, mixed crystal forms, solid solutions, co-crystals, and other forms.
In certain embodiments of the present methods, solid samples are generated in receptacles through a suitable means of solidification. Typically, a solution containing a compound or mixture to be solidified and a solvent is placed in a receptacle defining a capillary space, such as a capillary tube. The compound or mixture can be present in a solution below, at or above its saturation point at a given temperature at the time it is placed in a capillary tube. Through evaporation, the use of an antisolvent, temperature variation, and/or other suitable means, the system reaches a point where solidification begins. After a suitable amount of time, when solid or semisolid appears, the resulting sample is ready for analysis.
Any suitable crystallization technique may be employed for obtaining crystals. For example, crystals may be obtained through cooling, heating, evaporation, addition of an antisolvent, reactive crystallization, and using supercritical fluids as solvents. Additionally, melt crystallization techniques may be used to generate a solid form. Through such techniques, the use of a solvent can be avoided. In such techniques, formation of crystalline material is from a melt of the crystallizing species rather than a solution. Additionally, the crystallization process may be done through sublimation techniques.
Crystallization may be performed as a seeded operation or an unseeded operation. In a seeded operation, a selected quantity of seed crystals is included in the system. The characteristics of the seed crystals typically influence the characteristics of the crystals generated from the system. Crystallization may be performed by heterogeneous or homogeneous mechanisms.
In other embodiments of the present methods, the form is generated other than by crystallization. The sample may be in the form of a melt that is then added to the capillary tube and allowed to solidify in an amorphous form. Alternatively, the mechanism by which solidification is accomplished may include gel diffusion methods, thin-layer deposition methods, or other suitable methods. Other thermodynamic and kinetic conditions may be employed to solidify the compound or mixture. Cooling of a saturated solution is a typical thermodynamic condition. An addition of a solution of the compound or mixture to an excess of cold anti-solvent is a typical kinetic condition.
Any material capable of forming a solid or semisolid may be used in the present methods. In particular, the present methods are especially suited for materials characterized by molecules which are associated by non-bonded interactions (e.g. van der Waals forces, hydrogen bonding, and Columbic interaction).
The present methods may be advantageously used with small organic drug molecules having solubility of at least 1 mg/mL in ethanol at ambient conditions. The present methods are also contemplated for use with large organic molecules and inorganic molecules. Examples of compounds having more than one solid form include 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile and 4-methyl-2-nitroacetanilide, each of which may be different colors in connection with different forms, and novobiocin and furosemide, which are discussed above. This list cannot be exhaustive as the present methods may provide significant benefits for novel compounds and mixtures whose identities, or at least whose possible forms, are not yet identified.
The generation of a variety of forms is an important object of screening. A sufficient number of diverse processes and conditions should be employed to maximize the likelihood that a high percentage of possible solid forms of a chemical compound is generated. Samples should be generated under various thermodynamic and kinetic conditions.
It is preferable that the generation of solid and/or semisolid forms within the receptacles is carried out under a wide variety of conditions. For example, solids should be generated in the presence and absence of various solvents, as the solvent may play a role in the formation of certain forms.
As another example it is also preferable to prepare samples under different conditions of temperature and pressure, as different solid forms may be favored by different conditions.
The various forms generated may be identified by any suitable method, including but not limited to visual analysis (such as when different forms exhibit different colors), microscopic analysis including electron microscopy, thermal analysis such as determining the melting points, conducting diffraction analysis (such as x-ray diffraction analysis, electron diffraction analysis, neutron diffraction analysis, as well as others), conducting an infrared spectroscopic analysis, or conducting other spectroscopic analysis. Any appropriate analytical technique that is used to differentiate structural, energetic, or performance characteristics may be used in connection with the present methods.
The classifying step may comprise classifying the generated form(s) according to any of the analytical results, such as appearance, solubility, or x-ray diffraction pattern.
In a preferred embodiment, a synchrotron may be used as the source of radiation for conducting diffraction analyses. A synchrotron is a type of particle accelerator, which emits high energy, focused radiation. Synchrotron radiation is the byproduct of circulating electrons or positrons at speeds very close to the speed of light. Synchrotron radiation contains all the wavelengths of the electromagnetic spectrum and comprises the most intense source of wavelengths available in the x-ray and ultraviolet region. Synchrotron radiation allows analysis of smaller quantities of sample that would be difficult to analyze using other sources of x-ray radiation.
One location for research using synchrotron radiation is the Stanford Synchrotron Radiation Laboratory (SSRL), which is funded by the Department of Energy as a national user facility. Another location is Argonne National Laboratory, which is available to outside users on a fee basis.
Synchrotron radiation may be used to study structural details of solid samples with a resolution not practically attainable using traditional x-ray instrumentation. This may enable differentiation between different polymorphic forms or compounds that is not attainable with other x-ray radiation sources.
Preferably, the present methods comprise generating more than one form such that a distribution of forms is obtained.
However, by generating solid forms in receptacles defining capillary spaces, one may favor the formation of a variety of solid forms and increase the likelihood of generating all or a high percentage of possible forms.
The present methods can significantly assist in the identification of the form of a compound or a mixture that is most stable or has other properties that make it preferable over other forms. For example, the present methods can be used as part of a screening method and can improve the likelihood of identifying a form having biological activity such as better bioavailability, solubility, or adsorption characteristics. In some cases, an identified form may have better activity as an active agent.
After the sample is placed in a receptacle, the receptacle may be centrifuged. Centrifugation may be employed for a variety of reasons. First, centrifuging may assist evaporation or concentrate solid or semisolid material at one end of a capillary space. This has advantages in connection with in-situ analysis, in that the generated form will be located at a consistent place in the receptacle. Also or alternatively, centrifuging may be used to provide additional environmental variation, which is desirable in a screening method.

Methods of screening for possible solid forms


Adjustable landscaping ergonomic pads of various shapes adapted for covering the soil around the trunks of shrubs, trees, and garden plants to completely eliminate and retard the growth of weeds and other undesirable plants.

1. Field of the Invention
The present invention relates generally to plant protectors. More specifically, the present invention is a landscaping fibrous pad cover having various shapes with some apertured in the center, and adapted for covering the soil around the trunks of shrubs, trees, and garden plants to completely eliminate or retard the growth of weeds and other undesirable plants.
2. Description of Related Art
The related art of interest describes various plant protecting covers, but none discloses the present invention. There is a need for a plant cover, which is inexpensive and satisfies the protection needed to prevent weeds from growing around the desired plant, and yet permit some watering from the absorption of water by the cover.
The related art will be discussed in the order of perceived relevance to the present invention.
U.S. Pat. No. 5,396,731 issued on Mar. 14, 1995, for Steven E. Byrne describes a mulch composition pad for trees having a circular configuration with a keyed slot leading from the outside edge to the centered aperture. The composition is made from ground rubber tire granules 0.25 to 0.75 in. large, rubber powder or buffings, and less than an inch long tire fibers of rayon or nylon mixed with a curable binder of latex or urethane, iron oxide pigment as a coloring agent, diatomaceous earth, a catalyst, and some ultraviolet (UV) light stabilizers and antioxidants. Grass does not grow through the mulch pad. The mulch pad is distinguishable for requiring ground rubber products, iron oxide pigment, diatomaceous earth, a catalyst, UV light stabilizers, and anti-oxidants.
U.S. Design Pat. No. 413,495 issued on Sep. 7, 1999, for Ronald D. Carter describes an ornamental circular domed metal tree protector made from a wire mesh attached to metal half-rings. The tree protector is distinguishable for requiring a metal mesh protector.
PCT Patent Application No. WO 90/01256 published on Feb. 22, 1990, for Svein Lilleengen describes a slotted cover disk made from fermented dung and impregnated with growth promoting and binding substances for promoting plant growth and inhibiting weed growth. The cover disk is distinguishable for being limited to a flat slotted disk and fermented dung materials.
U.S. Design Pat. No. 283,003 issued on Mar. 18, 1986, for DeWitt McKinley describes an ornamental one-piece metal tree grate in either a square or circular flat shape having radial indentations on top and a square grid pattern on the bottom. The grates have an open circular center. The tree grates are distinguishable for requiring a unified flat metal construction.
U.S. Pat. No. 5,085,001 issued on Feb. 4, 1992, for Michael S. Crawley describes a stabilized mulch skirt comprising a single sheet having an axial opening and a slit extending to the periphery, and a plurality of adjustment strips formed around the axial for custom-sizing at the site to fit the trunk. A plastic or steel ring anchored by pins stabilize the skirt. The device is distinguishable for requiring a mulch skirt.
U.S. Pat. No. 3,305,969 issued on Feb. 28, 1967, for Merle E. Mattson describes a tree or plant protector collar device comprising a circular porous plastic material having a centered aperture with a slit to the periphery of the collar. The collar is distinguishable for requiring a porous plastic material.
U.S. Pat. No. 5,211,338 issued on May 18, 1993, for Diva C. Leite et al. describes a planar sprinkler shield device of unknown composition for minimizing plant growth underneath arranged around a sprinkler head inside its centered aperture, and having frangible portions with spikes to permit geometric tailoring. The device is distinguishable for requiring frangible regions of a circular shape which is staked down.
U.S. Pat. No. 5,323,557 issued on Jun. 28, 1994, for Donald J. Sonntag describes a flexible landscaping mat (unknown material) comprising three circular regions and a centered aperture for a tree trunk or a post. The inner region has guide rings for sizing the hole to the tree trunk. A slit extends from the periphery to the center or through the diameter. The intermediate region has scored circles for staking and ribs for retaining ornamental materials such as rocks, bark, wood chips, or mulch. The mat is distinguishable for requiring a textured mat.
U.S. Pat. No. 5,522,176 issued on Jun. 4, 1996, for Gene C. Suttle describes a landscaping ground cover to be placed around a tree or a shrub to prevent the growth of grass, weeds or other foliage, and to protect the tree or shrub. The cover comprises a circular sheet of flexible vinyl plastic having a square perimeter path for shaping the cover, a series of concentric circular paths or recessed channels in the center and upper surface, and a plurality of drainage holes. The ground cover is distinguishable for laying flat on the ground around a tree or shrub, and requiring shaping to fit the ground area.
U.S. Pat. No. 6,090,466 issued on Jul. 18, 2000, for William G. Kartisek describes a nylon pruning cloth which has a split down its center and terminates at a central circular section for the tree trunk. A pouch is sewn on one side of the cloth to collect pruned clippings. Pulling cords and four circular rings are formed at the opposite end. The pruning cloth is distinguishable for requiring a pouch, pulling cords, and apertures for the cords.
U.S. Pat. No. 6,276,869 B1 issued on Aug. 21, 2001, for Kuniaki Yakushinji describes an opaque circular and convex synthetic resin plate having two equal segments attachable with fasteners, and a center hole having an outwardly curving neck for controlling weeds around a tree root. The weed control plate is distinguishable for being a bowl-shaped inflexible cover placed upside down.
U.K. Patent Application No. GB 2 207 845 A published on Feb. 15, 1989, for John M. Moore describes a cover for a plant container comprising a pliable circular member having a centered aperture and a slot going to an area with a plurality of radially slotted segments to permit the size of the aperture to expand. The cover is distinguishable for being limited only to shape changing to allow greater inside space.
None of the above inventions and patents, taken either singly or in combination, is seen to describe the instant invention as claimed.
The present invention is an adjustable landscaping pad adapted for covering the soil around the trunks of shrubs, trees, and garden plants to completely eliminate or retard the growth of weeds and other undesirable plants. The covers are made from fibrous woven cloth such as jute, hemp, cotton, nylon, Mylar (TM) rayon, and polyester. Jute and hemp are considered burlap cloths. The preferred cloths have either a circular form with a centered aperture or a rectangular length with slits on one long side to spread out on the ground. A preferred embodiment has two cords woven into the upper portion of a circular fibrous cloth having a slot traversing from the outside edge to a centered aperture for wrapping around a trunk or stem. The cords tighten the cover in opposite directions. Other embodiments can be simply tied externally by a separate cord to the trunk or stem. Other shapes such square, oblong, star, and triangular shapes are contemplated which would depend on the arrangement configuration of plant or plants to be protected. These cloths have a valuable property when they are tied around the stem or trunk of a plant of absorbing and distributing the absorbed water, and preventing weed growth. Other ergonomic advantages are providing insulation during cold weather and minimizing the use of herbicides and insecticides. These covers can have various other shapes such as triangular, square, oblong, and star-shaped, and are also inexpensive to make and produce.
Accordingly, it is a principal object of the invention to provide an inexpensive ergonomic root cover for plants to prevent the proximate formation of weeds, provide insulation and supply absorbed water.
It is another object of the invention to provide an inexpensive root cover having various shapes such as circular, rectangular, square, star, oblong, and triangular shapes.
It is a further object of the invention to provide a preferred first, second and third embodiments of an inexpensive root cover having a circular shape with two hemmed tying cords, one hemmed cord, and no cord respectively, positioned to tighten in opposite directions.
Still another object of the invention is to provide a fourth preferred embodiment of a rectangular cover having slits on one side for spreading out on the ground.
It is an object of the invention to provide improved elements and arrangements thereof in an apparatus for the purposes described which is inexpensive, dependable and fully effective in accomplishing its intended purposes.
These and other objects of the present invention will become readily apparent upon further review of the following specification and drawings.


Radioactive seeds, particularly 1-125 radioiodine seeds are sterilized by being subjected to dry heat at a temperature of at least 140xc2x0 C., preferably 150-200xc2x0 C. A container having loose sterile radioactive seeds therein is disclosed. The container is preferably of glass with a label and a removable heat-resistant silicone closure.

The present invention relates to sterile radioactive seeds, and to a dry heat method for sterilising seeds. It is particularly concerned with sterile loose seeds which may be presented in a closed container, where the sterilisation method used is dry heat.
Radioactive seeds are radioactive permanent implants for the treatment (brachytherapy) of various clinical conditions, such as cancer, particularly prostate cancer, or restenosis. Such seeds comprise a radioisotope (typically 125I or 103Pd) sealed within a biocompatible container (typically titanium or stainless steel). Each patient dose is individually calculated depending on the size of the tumour, but is typically in the range 50-120 seeds per patient when treating prostate cancer. The seeds are implanted in a three-dimensional matrix according to calculated dosimetry. The seeds are sufficiently small to be loaded into implantation needles.
The radioactive-isotope of choice is 125I. This isotope has a half life of 60 days, short enough to permit implanted seeds to be left permanently in a patient""s body without inflicting excessive long term damage. 125I emits low energy X-rays (30 KeV), which ensures that the volume of treated tissue is mainly confined to the locality of an implanted seed, i.e. the tumour.
In one currently available radioiodine seed, iodine-125 is adsorbed on to a silver rod and encapsulated in a welded titanium capsule. The silver rod acts as an X-ray marker. The seeds are cylindrical, 4.5 mm long and 0.8 mm diameter, designed to fit into a needle or catheter with an internal diameter of 1 mm. Such seeds are described in U.S. Pat. No. 4,323,055. These radioiodine seeds are commercially available. They are designed and manufactured to meet temperature test 5 of ISO 2919: 1999(E). This test involves holding the seeds at xe2x88x9240xc2x0 C. for 20 minutes; at +600xc2x0 C. for one hour; and subjecting the seeds to thermal shock from +600xc2x0 C. to +20xc2x0 C. It may be noted that these tests are designed simply to assess product safety performance when subjected to various stresses. Designs which do not release radioactivity pass the test. Hence such tests are not part of routine seed manufacture, but form part of the validation of a given seed design. Consequently, any deterioration in performance of the seed product as a result of the test, is not measured.
Brachytherapy seeds are commercially available in three forms:
a) loose, non-sterile, supplied in a screw cap vial;
b) sterile in a flexible suture;
c) sterile in a stiffened suture.
The last product (sold under the RapidStrand trademark) comprises an initially flexible elongated bio-absorbable material having seeds incorporated therein at regular intervals. The strand is subsequently heated which makes it less flexible, to aid the process of implanting in or around a tumour. As noted in U.S. Pat. No. 5,460,692, this RapidStrand product is marketed in a sterile state by virtue of having been treated with a chemical sterilising agent. However, chemical sterilisation is problematic as discussed below and is not suitable for loose seeds.
It may be noted that, despite being radioactive, the radioiodine seeds are not self-sterilising. This is because the radiation dose at the surface of the seed is insufficient to cause the required degree of killing of micro-organisms. Customers who buy non-sterile loose radioiodine seeds need to sterilise them before use. An instruction leaflet accompanying the seeds teaches the use of steam sterilisation and specifically advises against the use of dry heat or chemicals to sterilise the seeds. However any unnecessary manipulation of radioactive seeds by a customer is inherently undesirable. Since the seeds contain a volatile radioiodine isotope, any handling operation that involves heating is particularly undesirable. Moreover regulations in Europe do not permit the sale of radioactive seeds in a non-sterile form if they are to be permanently implanted in the human body. There is thus a need for a supply of loose sterile radioactive seeds. This invention addresses that need.
In one aspect the invention provides a method of sterilising one or more radioactive seeds. The method comprises subjecting the radioactive seeds to dry heat for a time sufficient to effect sterilisation; and subsequently cooling the radioactive seeds. The temperature of the dry heat sterilisation process should be at least 140xc2x0 C., preferably 150-200xc2x0 C., most preferably 160-165xc2x0 C. The term xe2x80x98dry heatxe2x80x99 is used in the field of sterilisation, and denotes that the heating is achieved without contacting the seeds with either boiling water or steam, ie. in contrast to moist heat. The term xe2x80x98coolingxe2x80x99 encompasses both a passive process (eg. removing or switching off the source of heat) so that the seeds cool slowly to ambient temperature, and a more active process (eg. moving the seeds to a cooler area, or application of a cooling means such as a fan), so that the seeds cool more quickly.
In another aspect the invention provides a product prepared by the above dry heat sterilisation process. The product comprises one or more radioactive seeds in a sterile condition, preferably in a closed container, wherein the seed(s) have been sterilized by dry heat.
In another aspect, the invention provides a product comprising a closed container containing one or more radioactive seeds in a sterile condition, wherein the radioactive seeds are free of moisture and of chemical residues characteristic of chemical sterilisation, and wherein the product is free of degradation characteristic of sterilisation by gamma irradiation.
The dry heat process of the present invention may be carried out by use of a variety of heating means capable of achieving the required substantial absence of moisture and temperature control for the required time, such as ovens (heated by conventional means such as electricity, gas or solid fuel); radiant heat (eg. from hot wire filaments); immersion in a bath of heated high-boiling organic solvent (eg. an oil such as silicone); flames; or infra-red radiation. Heating techniques which require an additional step, such as the removal of residual high-boiling solvent or surface combustion deposits are less preferred. It is preferred to use ovens, which may be electrically or gas heated, and deliver heat via hot air, and which have a temperature-controlled environment. Microwave ovens not suitable, since such heating is not safe for metallic objects such as seeds, potentially risking rupture of the seed. Also, microwave heating would deliver heat to the inside of the seed, whereas the present invention requires that the outer surface of the seed is heated to sterilise that part of the seed which would be in contact with the human body. Ovens suitable for use in the present invention are commercially available in a variety of forms and sizes, and are preferably heated electrically and designed for laboratory use.
The dry heating of the present invention should preferably be carried out in an atmosphere which contains oxygen, and is preferably and conveniently carried out in air. The presence of oxidation facilitates the destruction of micro-organisms by an oxidative process. When the heating means is an oven, hot air is used to transfer the heat to the seeds to be sterilized. Hence, when the seeds are sterilized in a closed container, the headspace gas above the seeds in the container should contain oxygen, and is preferably and conveniently air at atmospheric pressure.
Whichever heating means is used, it is necessary to have adequate temperature control around the zone in which the seeds are to be heated. This temperature control may be achieved either manually, eg. by adjustment of the heat in response to temperature readings, or is preferably achieved automatically via a thermostatically controlled heating means, preferably as part of a temperature-controlled oven. The temperature at specific locations within the heating means used (eg. different areas or shelves within an oven), should be validated prior to use to show that the temperature delivered at the heating zone around the location(s) of the seeds is that required by the present invention. Once the coolest part of the heating zone used has been established, the temperature probe used during the dry heat sterilisation should always be located at that position, to ensure that the required minimum temperature is always achieved. The effectiveness of the sterilisation cycle at all parts of the heating-zone should be validated by demonstrating that authentic samples of micro-organisms at the various locations are killed, eg. by showing that, when cultured following the dry heat cycle, there is no growth. The temperature readout may preferably be recorded (eg. as a graphical printout or electronic record) during the dry heat sterilisation process. This record can usefully be included as part of the batch records as evidence of sterilisation of the seeds.
The duration of the dry heating is dependant on the temperature adopted. The British and European Pharmacopoeias recommend a minimum holding time of 120 minutes at a temperature of at least 160xc2x0 C. for dry heat sterilisation. Shorter minimum holding times may conceivably be used at higher temperatures, eg. approximately 60 minutes at 170xc2x0 C., and 30 minutes at 180xc2x0 C., but it is preferred to adopt the Pharmacopoeia protocols. The timing of the dry heating can be carried out manually, or is preferably carried out automatically using a suitable oven having temperature programming controls, eg. microprocessor-controlled.
Preferably, the seeds are loose. Preferably the seeds are provided in a closed container, of glass or a plastic material capable,of withstanding the sterilisation temperature. While a sealed glass ampoule can be used, the container is preferably a glass vial having a removable closure e.g. made of silicone or other material capable of withstanding the sterilisation temperatures involved. The closure must be gas tight and is normally anchored in position with an overseal, which is typically crimped on and metallic in nature. Such an arrangement ensures that the environment around the sterile seeds within the container is maintained. For ease of handling by a customer, loose seeds present within a container are preferably in a drystate.
The radioactive seeds of the present invention may also have been modified so that they are echogenic, ie. they reflect ultrasound of clinical frequency (ca. 7.5 MHz) over a wider range of angles to the ultrasound transducer than conventional seeds. Such echogenic seeds may have at least a portion of their outer surface roughened, as described in commonly assigned application PCT/GB99/03668. The roughening may take the form of grooves, depressions, scratches or the like on the surface of the seed container. The grooves may be arranged randomly on the surface or in more regular patterns eg. in geometric shapes and patterns such as squares and circles, or as lines running substantially parallel or perpendicular to an axis of the seed or in a helical arrangement. Preferably, the grooves etc. are not arranged in a highly repeating pattern with more than one repeat per quarter wavelength as such patterns may act as optical gratings and lead to a loss of omnidirectionality in the echo return. Preferably, the irregularities or discontinuities are in the form of a helical groove (eg. with a sinusoidal profile) on the surface of the container. The pitch of the helix may be chosen to give first order maxima in the intensity of the reflected ultrasound at certain specific angles with respect to the orthogonal orientation. For example, for a conventional radioactive seed 4.5 mm long and 0.8 mm in diameter, a pitch of about 0.6 mm will give a maximum at 10xc2x0 from orthogonal with 7.5 MHz ultrasound, whilst a pitch of about 0.3 mm will give a maximum at 20xc2x0 from orthogonal. For such a seed the depth of the groove from peak to bottom should be approximately 40 to 60 xcexcm. The spacing of repetitive grooves along a source""s axis should not be too close, otherwise a minimum of ultrasound scattering may occur at angles close to 90xc2x0 (i.e. orthogonal). The roughening may be produced by a variety of different methods. Thus, the outer surface of the seed container may be roughened or shaped by forcing the source through a ridged or serrated dye or a threading device to impart grooves on the surface. A similar effect may be produced by milling. The surface may also be roughened as a result of mechanical friction, for example by use of a wire brush or a file, or a suitable grade of sandpaper, e.g. a coarse grade. The outer surface may also be etched, for example using a laser or water-jet cutter, or by electrolytic etching. Blasting, for example sand blasting, may also be used. Blasting may be done dry or wet as in water-jet blasting.
Batches of radioactive seeds, comprising different numbers of radioactive seeds in the range 1-200, e.g. 1-100, preferably 1-50 radioactive seeds, may be sterilized using the method of the present invention. Preferably these batches are provided in closed containers each of which carries during sterilisation a label or marker indicating the contents of the closed container.
The choice of dry heat for sterilising radioactive seeds was not an obvious or a natural one. To illustrate this, there follows a discussion of the various sterilisation methods available. The principal choices are:
(i) aseptic handling,
(ii) steam sterilisation,
(iii) steam (porous load),
(iv) chemical (e.g. ethylene oxide),
(v) gamma irradiation,
(vi) dry heat.
(i) Aseptic Handling
This is one approach for producing sterile seeds. In effect this means that the whole seed manufacture process is carried out under aseptic conditions (clean rooms, air filtration etc). This is not an attractive prospect since it makes manufacture difficult, labour-intensive and expensive especially when radioactive safety and handling precautions are also necessary. Hence so-called xe2x80x98terminal sterilisationxe2x80x99 (i.e. sterilisation only after all the components have been assembled in a non-sterile environment) is much preferred. (ii)-(vi) are the principal options for terminal sterilisation.
(ii) Steam Sterilisation (Moist Heat).
This is typically carried out using an autoclave. This process involves the use of moist heat, usually as saturated steam at temperatures above 100xc2x0 C. This achieves the destruction of micro-organisms by the irreversible denaturation of enzymes and structural proteins of the microorganism. When a sealed container of loose seeds is to be sterilized, the implication is that there must be water within the closed container. This is to ensure good heat transfer, ie. steam must condense on the surfaces. The phase change is responsible for the dispersion of energy, ie. the condensation of the steam releases heat which is imparted to the surface. This means that, although sterile, the product to be shipped to the customer would be wet within the container/vial. For a vial in which loose seeds are currently sold, it is estimated that ca. 0.5 cm3 of water would be required in a vial of 10 cm3 volume. This in itself makes for an unattractive product, and poses handling problems for the clinician, who must dry the seeds before use etc.
An unforeseen problem with this is that in transit (e.g. when being shipped in cold climates or in aircraft holds), the water may freeze causing great pressures which may be sufficient to risk rupturing the welds of the seeds. Thus, although steam sterilisation is a standard technique, it has significant disadvantages when applied to the commercial supply of sterile loose seeds (which need to be shipped within a container, containment or packaging to maintain the sterile integrity in transit).
If steam sterilisation is used in conjunction with an open vial of seeds, then additional steps become necessaryxe2x80x94first to dry the inside of the vial, and then to stopper the vial under aseptic conditions. Hence this then becomes no longer the preferred xe2x80x98terminal sterilisationxe2x80x99 step, but requires further sterile handling procedures.
(iii) Steam Sterilisation (Dorous Load).
Steam sterilisation may conceivably be used with suitably porous closures/stoppers to permit ingress and egress of the steam, but this poses significant technical problems in ensuring complete removal of residual water and additional shielding or secondary containment required in case there is a leak of radioactivity from any of the seeds.
(iv) Chemical. e.g. Ethylene Oxide (EtO).
Ethylene oxide gas (EtO) is used to sterilise some seed products, eg. Nycomed Amersham""s RapidStrand. Use of this material has several serious problems. First it is highly toxic, hence thorough degassing to ensure that removal of EtO is complete is essential. It is also inflammable,xe2x80x94a significant risk when being used in conjunction with radioactive plant. As a consequence of the need for thorough degassing, sterilisation using EtO is slow. As with (iii) above, porous packaging materials Would be required to use EtO for terminal sterilisation. EtO is also known to leave trace organic residues (ethylene oxide itself, ethylene chlorohydrin, ethylene glycol and ethylene oxide condensation polymers) on the surface of the materials sterilized.
Manifestly, chemical sterilisation of a closed container is not effective to sterilise the contents of the container. If radioactive seeds are subjected to chemical sterilisation, they must be introduced into closed containers subsequently and this adds complications to the process.
Other chemical alternatives to EtO exist, but direct use of liquid chemicals on the seeds runs the risk of damage to the seed capsule; especially to the weld with attendant risk of radioactive leakage etc. As with EtO, there is also the issue of both achieving and demonstrating complete removal of the chemical used since the seeds are destined to be implanted in the human body.
There is also the possibility that some chemical treatments, can render the outer surface of the seeds xe2x80x98stickyxe2x80x99, which would make subsequent loading into needles and implantation by the user more difficult.
(v) Gamma Irradiation.
Irradiation with a high energy gamma emitter (e.g. 60Co) is a standard technique used for the terminal sterilisation of medical materials. A problem with this approach is that significant plant is required, with heavy shielding of the gamma-emitting radioisotope. It is also the case that conventional gamma irradiation plant is not configured to deal with products which are themselves radioactive. Hence there are problems of suitable containment and shielding etc, for a significant volume of gamma irradiation plant and equipment. It may be also that some parts of the seed packaging may be damaged by the high energy gamma rays. Thus if glass materials are used (e.g. a vial), the glass would be browned in colour by the irradiation. Any labels on the materials would probably also be discoloured.
(vi) Dry Heat
This method involves heating a product at a temperature of at least 140xc2x0 C., preferably 150-200xc2x0 C., preferably at least 160xc2x0 C. Sterilisation in this case is believed to occur via oxidation of the microorganism cell constituents. Sterilisation using dry heat is known to require higher temperatures and longer exposure times than moist heat. The product is held at the temperature for a time sufficient to effect sterilisation, typically for a minimum of 2 hours, and is then cooled or allowed to cool.
The dry heat seed sterilisation process of the present invention has the advantage that it is quick, uses equipment typically found in a production laboratory, is relatively easy to validate and control, and gives a very high sterility assurance level. The sealed seed container does not need to be open during the process, hence it is a genuine terminal sterilisation. There is no need for specific assays or checks to ensure removal of toxic chemicals, and the product is in a form which is convenient to use for the customer.
As discussed, this approach to seed sterilisation is not one which would be immediately apparent. Strong heating of a sealed capsule containing a volatile radionuclide does imply an attendant risk of internal pressure developing. Clearly any rupture of the capsule or weld would cause a serious escape of radioactivity. The greater the number of seeds heated in this way, the greater would be the perceived risk of problems arising. It is also the case that, depending on how it is done, seeds which are very small (cylinders ca. 4.5 mm longxc3x970.8 mm diameter), radioactive and hot (temperature) present significant handling problems.
As previously noted, currently available radioactive seeds can withstand heating to 600xc2x0 C. for one hour plus thermal shock from 600xc2x0 C. to +20xc2x0 C. without loss of radioactive integrity. However, it would be anticipated that such heating might change the chemical nature of the radioisotope within the seed (eg. via oxidation), or redistribute the radioisotope within the seed, leading to a change in the radiation dosimetry contours (xe2x80x9cisodose curvesxe2x80x9d) around the seed. Although dose distribution around each individual seed is not perfectly isotropic, substantially uniform dosimetry is important for the desired medical treatment, hence any such change would compromise the efficiency of the product. In tests to validate the present invention, it has been determined that dry heat sterilisation for 2 hours at 160xc2x0 C. does not compromise the substantially isotropic dose distribution around each individual radioiodine seed, and the same would be expected to be true for 103Pd seeds.
Preferred closed containers according to this invention are glass vials with septum seals or other rubber or plastic closures. A problem with such rubber or plastic closures in general is that strong heating can promote leaching of unwanted organic impurities from the closure, potentially contaminating the seeds. Clearly this would be very unsatisfactory for a medical product. Also the closure not deform on heating, i.e. the seal must be maintained. Many standard vial closures simply would not withstand the temperatures necessary for dry heat sterilisation. One silicone closure has been identified which has the necessary properties. That is a silicone stopper 1185 marketed by The West Company Danmark AS, and reported to be made from a liquid silicone rubber Silastic(copyright) 9280/40E.
In normal pharmaceutical manufacture, batches typically comprise multiple units of the same material. For the present product, the situation is different. This is because the physician orders a variable number and/or activity of seeds depending upon his/her calculation of the dosimetry required for the individual patient therapy. Consequently, each closed container to be dry heat sterilized may contain either a variable number of seeds (e.g. from 1 to 50), or the same number of seeds but of a different activity level, i.e. each container is different. Preferably a plurality of containers of radioactive seeds, comprising the same or different numbers or activities of radioactive seeds, are sterilized together. This can conveniently be achieved by eg. loading the containers into a tray which can then be loaded into the oven or other means used to supply the dry heat.
The variable number and/or activity of seeds means that the labelling of radioactive content, dose at extremities of the packaging etc. could be very different. As a result, it is convenient to have traceability of an individual vial right through the process. Thus it is preferred that the seed container is labelled or otherwise marked to show the number of seeds contained, radioisotope activity content etc in such a way that the mark or label remains in place during the dry heat sterilisation step. As might be expected, many paper-based labels do not withstand the oven temperatures used and darken in colour, going brown. This is obviously undesirable for the product presentation. Similarly, whatever printing method is used for the labels must also be able to withstand the conditions without loss of information. The solution to this problem is the use of particular plastic labels, having printing thereon that can withstand the heat. Thermal transfer ribbons based on coated white polyester film and marketed by Armor under the Trademark AXR7, have been found suitable for use in the present invention.


A thin walled, plastic hot-fill container has a closable neck, a shoulder portion situated below the neck, a base, and a body portion connecting the shoulder portion to the base. The body portion includes a label mount area bounded by upper and lower margins having a plurality of vacuum panels with vertical land areas separating each adjacent pair of vacuum panels. Each vacuum panel includes an upper area and a lower area, the upper and lower areas of each vacuum panel being mutually asymmetric and connected by a tapering geometry providing a range of pressure response through varying flexibility without significant movement of the components parts of the vacuum panels.

The present invention relates to blow-molded containers of biaxially oriented thermoplastic materials, typically polyethylene terephthalate, that are especially adapted to be filled with a hot liquid or semi-liquid product and hermetically sealed, and which are generally referred to as thin-walled hot-fill containers. The invention particularly relates to improvements in container design to achieve a filled container that, when cooled, retains a desired container configuration despite the development of a partial vacuum within the container, and provides enhanced support of any label applied to the container even when subjected to sidewall impact.
Thin-wall hot-fill containers are typically used for packaging of liquids which must be placed in the container while hot to provide for adequate sterilization. During the filling process, the container is subjected to elevated temperatures on the order of about 85xc2x0 C. and may be subjected to some small positive internal pressures on the order of about 0.2 bar. The container is immediately capped so that no appreciable cooling of the container contents occurs prior to the hermitic sealing. As the product subsequently cools, a negative internal pressure is formed in the sealed container. Any flexible wall of the container will elastically deform inward to the extent necessary to at least partially reduce the negative pressure within the container. Thin-wall hot-fill containers of the prior art typically include a plurality of vacuum panels specially designed to elastically deform in a controlled manner, thus preventing any large uncontrolled shape distortion. The vacuum panels are typically arranged around the circumference of a middle portion of the container and are typically covered by a wrap-around label held within the margins of an area commonly identified as the label panel.
Many styles and geometric patterns have been developed for the vacuum panels. The variations are all intended to address various concerns about the container performance and shape retention when dropped, when vertically stacked, when pinched by manually gripping the container, etc. To address these concerns the vacuum panels often include raised central wall portions, post areas between the vacuum panels, and circumferential land areas above and below the vacuum panels, longitudinal and circumferential recessed ribs, hinge portions, etc. As the wall thickness of the containers is reduced from the already thin dimension of typically less than xc2xd mm, the various problems associated with thin-wall hot-fill containers become exacerbated. A particularly difficult problem is presented by side impacts that tend to permanently deform the sidewall of the container. A more general problem is the competing desires of providing sufficient stiffness in specific areas of the label panel, while still permitting other areas to yield in the intended manner for successful hot-fill performance.
What is needed is a thin wall hot-fill container that provides a large range of flexibility while retaining sufficient support of any label applied to the container even when subjected to sidewall impact.
These competing needs are satisfied by a container of the present invention, which has a closable neck, a shoulder portion situated below the neck, a base, and a body portion connecting the shoulder portion to the base. The body portion includes a label mount area bounded by upper and lower margins. A plurality of vacuum panels are situated in the label mount area with a land area separating each adjacent pair of vacuum panels. Each of the vacuum panels includes an upper edge and a lower edge, each edge being spaced from the upper and lower margins of the label mount area. Each vacuum panel includes an upper area adjacent the upper edge and a lower area adjacent the lower edge, the upper and flower areas of each vacuum panel being mutually asymmetric. As an example, either the upper or lower area of each vacuum panel comprises a horizontally cylindrically concave surface while the other area of each vacuum panel comprises a plane inclined at a shallow angle with respect to a horizontal plane. Additionally, the label mount area includes a circumferential recessed rib located in the land area adjacent to the margin of the label mount area nearest to the end of the vacuum panel including the horizontally cylindrically concave surface.
Each of the vacuum panels of a thin-walled hot-fill plastic container of the present invention includes a central portion joining the upper area and the lower area, the central portion preferably including a central land area and side portions coupling the central land area to the adjacent land areas separating adjacent vacuum panels from each other. In a preferred embodiment, the side portions of each vacuum panel include a tapered geometry from the upper area to the lower area. The tapered geometry can comprise, for example, a conical surface section of decreasing radius of curvature from the upper area to the lower area.
The tapered geometry and the differences between the upper and lower areas evokes a vertically asymmetric pattern to the vacuum panels that achieves a large range of pressure response through varying flexibility without significant movement of the components parts of the vacuum panels. The shallow angled portion at one end of the vacuum panels and the circumferential recessed rib located adjacent to the other end of the vacuum panels provide the required stiffness to resist all but the most significant sidewall impacts, thereby ensuring both the necessary performance and appearance of the container within the margins of the label mount area.

Hot fill container with vertically asymmetric vacuum panels