Methods for whitening teeth including contacting teeth with an effective amount of particulate bioactive glass are disclosed.

The present invention relates to methods for whitening, lightening, bleaching or removing stains from teeth using certain bioactive glass compositions.
A tooth is comprised of an inner dentin layer and an outer hard enamel layer that is the protective layer of the tooth. The enamel layer of the tooth is naturally an opaque white or slightly off-white color. It is this enamel layer that can become stained or discolored. The enamel layer of the tooth is composed of hydroxyapatite mineral crystals that create a somewhat porous surface. It is believed that this porous nature of the enamel layer is what allows staining agents and discoloring substances to permeate the enamel and discolor the tooth. In addition, the tooth naturally acquires a film called pellicle, made up of salivary glycoproteins. The pellicle may also acquire stain. As the terms xe2x80x9ctoothxe2x80x9d or xe2x80x9cteethxe2x80x9d are used herein, they are intended to mean a material which is apatite and the acquired pellicle.
Many substances that a person confronts or comes in contact with on a daily basis can xe2x80x9cstainxe2x80x9d or reduce the xe2x80x9cwhitenessxe2x80x9d of one""s teeth. In particular, the foods, tobacco products and fluids such as tea and coffee, that one consumes tend to stain one""s teeth. These staining and discoloring substances can then permeate the enamel layer. This problem occurs gradually over many years, but imparts a noticeable discoloration of the enamel of one""s teeth.
WO 96/10985 discloses particulate bioactive silica containing glasses that can reduce pulpal irritation of a tooth and/or strengthen the structure of a tooth and therefore have use in the treatment of hypersensitive teeth. It is suggested that such glasses can consist solely of silicon oxide or silicon hydroxide or can contain one or more additional elements selected from Ca, P, Na, K, Al, B, N, Mg, Ti, or F. It is also suggested that it is advisable to use bioactive glass compositions comprising calcium and phosphate which can help induce remineralisation of dentin or alternatively to use separate sources of calcium and phosphate together with a bioactive glass not containing them.
WO 97/27148 discloses particulate bioactive and biocompatible glasses which can remineralise teeth and are of particular use in the reduction of dentin hypersensitivity.
Various treatment modalities have been used to whiten teeth including in-office bleaching, night guard bleaching and whitening toothpastes. However, the available methods and compositions are not satisfactory for a variety of reasons. For example, shade reduction has been less than ideal.
It has now been discovered that the above-noted bioactive glasses can be used to whiten teeth. Accordingly the present invention provides a method of whitening teeth, which comprises contacting a tooth structure with a tooth-whitening amount of a particulate bioactive and biocompatible glass.
These following words are intended to be given the same meaning here as would be accorded to them in their contemporary usage in the oral and dental care arts. More specific usage for the invention herein is described below.
The term xe2x80x9cwhiteningxe2x80x9d is used herein at all occurrences to include bleaching, lightening, or removing stain from the teeth.
The present invention provides a method for whitening, lightening or bleaching teeth. The method is also useful for removing stains from teeth. The method includes contacting teeth with an effective tooth-whitening amount of bioactive glass as disclosed in WO 96/10985 and WO 97/27148. Preferably, multiple applications are carried out. Each application may include between about 0.02 to 0.3 grams of bioactive glass. Suitably, the instant method of whitening teeth comprises contacting the teeth with said effective tooth-whitening amount of bioactive glass twice daily for two weeks or more. As the term xe2x80x9ctooth-whitening amountxe2x80x9d is used herein, it is intended to mean any amount that will result in a Vita shade guide lightening of one or more shades in a patient with a pre-treatment shade darker than A3.5 after 4 weeks of application twice daily for two minutes or more per application.
Accordingly the present invention provides a method for whitening teeth which comprises contacting teeth with an effective tooth-whitening amount of particulate bioactive and biocompatible glass comprising silicon oxide or hydroxide and optionally one or more elements selected from Na, K, Ca, Mg, B, Ti, Al, P, N or F.
Preferably the bioactive glass comprises at least Na, Ca and P, although it is possible to use simple sodium silica glasses together with external sources of calcium and phosphate. It will be understood by the skilled artisan that an external source of calcium and phosphate may be from saliva itself, or may be formulated into the oral hygiene composition.
A bioactive glass in accordance with the present invention is a glass composition that will form a layer of hydroxycarbonate apatite in vitro when placed in a simulated body fluid. Bioactive glasses in accordance with the present invention may be prepared by a variety of processes, e.g., melt-derived or sol gel and may have a variety of compositional elements and ranges. For example, the following composition by weight will provide an acceptable and preferred bioactive glass:
Bioactive glasses with these properties provide a more efficacious material for interaction with the tooth structure. The addition of fluoride in the glass composition will enhance and strengthen the tooth structure. Other examples include sol gel glasses having, for example, about 40 to about 86% by weight SiO2, substantially no amount of sodium, about 6-36% by weight Ca and about 2-12% by weight P2O5. A biocompatible glass in accordance with the present invention is one that does not trigger an overwhelmingly adverse immune response.
In, some embodiments of the present invention, extremely small particles are used. For example, particles that are in the range of 2 mm to submicron are beneficial. Particle size in accordance with the present invention is determined by scanning electron microscopy or laser light scattering techniques (e.g., Coulter LS100). Surprisingly, the relatively small bioactive particulate glass does not generate a significant immune response. Moreover, it is generally not engulfed by macrophages and rendered inactive in this application.
The compositions of the present invention may be formulated as oral hygiene compositions such as dentifrices, toothpaste, gels, powders, mouthwashes, irrigating solutions, and presentations for sucking or chewing such as gums, pastilles, tablets, and lozenges.
Such oral hygiene compositions suitably comprise between 0.1 to 50% by weight, preferably 1 to 25% by weight, more preferably 5 to 10% by weight of the bioactive glass.
In addition to the active ingredients, the oral hygiene compositions suitable for this invention will contain the usual carriers, binders, surfactants, humectants, coloring agents, pigments, antiplaque agents, anti-bacterial agents, bioadhesive-type agents, abrasives, anticaries agents, flavorings, sweeteners, bulking agents, and the like.
In the case of a toothpaste formulation, an abrasive typically includes amorphous, gelled, precipitated, or fumed silica, plastics particles; alumina, calcium carbonate, and zinc orthophosphate, insoluble metaphosphates and calcium pyrophosphate. Silica is an especially preferred abrasive for use herein. The patent and scientific literature is replete with examples of such abrasives. U.S. Pat. No. 4,822,599 listing a series of dentifrice abrasives also references commercial sources and methods for their preparation. The bioactive glass particles may replace all, some, or none of the abrasive currently used in toothpastes.
Inorganic thickeners may be included in the dentifrices of the present invention and include fumed silicas such as Cabosil available from Cabot Corporation, and thickening silicas including those available from J. M. Huber designated Zeodent 165. Organic thickeners such as natural and synthetic gums and colloids may also be incorporated in the dentifrice composition of the present invention. Examples of such thickeners include carrageenan (Irish moss), xanthan gum and sodium carboxymethyl cellulose, starch, polyvinlpyrrolidone, hydroxyethyl propyl cellulose, hydroxbutyl methyl cellulose, hydroxypropyl methyl cellulose, and hydroxyethyl cellulose (co-dried blends of microcrystalline cellulose/cellulose gum). The inorganic or organic thickener may be incorporated in the compositions of the present invention at a concentration of about 0.05 to about 2% by weight and preferably about 0.1 to about 1.5% by weight.
Fluoride-providing salts having anti-caries efficacy may also be incorporated in the oral compositions of the present invention and are characterized by their ability to release fluoride ions in water. It is preferable to employ a water-soluble salt fluoride providing about 10 to 5,000 ppm of fluoride ion and preferably about 1000 to 1500 ppm of fluoride ion. Among these materials are water-soluble alkali metal salts, for example, sodium fluoride, potassium fluoride, sodium monofluorophosphate and sodium fluorosilicate. Sodium monofluorophosphate is the preferred fluoride-providing salt.
Pigments used in the practice of the present invention include non-toxic, water insoluble inorganic pigments such as titanium dioxide and chromium oxide greens, ultramarine blues and pinks and ferric oxides as well as water insoluble dye lakes prepared by extending calcium or aluminum salts of FDandC dyes on alumina such as FDandC Green #1 lake, FDandC Blue #2 lake, FDandC RandD #30 lake and FDandC Yellow #15 lake. The pigments have a particle size in the range of 5-1000 microns, preferably 250-500 microns, and are present at a concentration of 0.5 to 3% by weight. Dyes are generally sensitive to the presence of the peroxide ingredient and are not included in the dentifrice although FDandC Green #3 has been found to be resistant to fading when CaO2 is present in the dentifrice.
Any suitable flavoring or sweetening material may be employed. Examples of suitable flavoring ingredients are flavoring oils, e.g., oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, and orange, and methyl salicylate. Suitable sweetening agents include sucrose, lactose, maltose, sorbitol, sodium cyclamate, perillartine, and sodium saccharin. Suitably, flavor and sweetening agents may together comprise from 0.01% to 5% or more of the preparations.
Various other materials may be incorporated into the oral composition components of this invention. Non-limiting examples thereof include preservatives, silicones and chlorophyll compounds, vitamins such as vitamins B6, 1312, C, E and K, antibacterial agents such as chlorhexidine, halogenated diphenyl ethers such as triclosan, desensitizing agents such as potassium nitrate and potassium citrate and mixtures thereof. These adjuvants are incorporated in the dentifrice in amounts which do not substantially adversely affect the properties and characteristics desired, and are selected and used in proper amounts, depending upon the particular type of component involved.
The making of particulate bioactive glasses are well known to those of ordinary skill in the art and need no further description here. Similarly, the making of gels, toothpastes, rinses, mouthwashes, gums, chewing gums are also well known in the art. Bioactive glasses can be introduced into these products by a variety of methods including simple mixing. Those of ordinary skill in the art will appreciate that in some circumstances it will be necessary to keep the bioactive glass from coming into contact with the aqueous or other components of the delivery vehicle to prevent the bioactive glass from pre-reacting. This can be accomplished by a variety of ways known to those of ordinary skill in the art including, for example, two piece syringes with a mixing chamber.
In addition to direct application of the bioactive glass to the teeth, the bioactive glass composition of the present invention can also be applied in a saline or distilled water based medium.
The present invention also provides the use of a bioactive and biocompatible glass as herein before defined optionally together with a source of calcium and/or phosphate in the manufacture of a composition for whitening teeth.

Methods and compositions for whitening teeth


This patent describes economical and environment-friendly processes for the synthesis of Al-containing non-Mg anionic clays. It involves hydrothermally reacting a slurry comprising a divalent metals source with a trivalent metals source to directly obtain Al-containing non-Mg anionic clay, at least one of the metal sources being an oxide, hydroxide or a carbonate. There is no necessity to wash or filter the product. It can be spray dried directly to form microspheres or can be extruded to form shaped bodies. The product can be combined with other ingredients in the manufacture of catalysts, absorbents, pharmaceuticals, cosmetics, detergents, and other commodity products that contain anionic clays.

1. Field of the Invention
This invention involves the preparation of Al-containing non-Mg anionic clays.
2. Description of the Prior Art
Anionic clays have a crystal structure which consists of positively charged layers built up of specific combinations of metal hydroxides between which there are anions and water molecules. Hydrotalcite is an example of a naturally occurring anionic clay, in which carbonate is the predominant anion present. Meixnerite is an anionic clay wherein OHxe2x88x92 is the predominant anion present.
In hydrotalcite-like anionic clays the brucite-like main layers are built up of octahedra alternating with interlayers in which water molecules and anions, more particularly carbonate ions, are distributed. The interlayers contain anions such as NO3xe2x88x92, OH, Clxe2x88x92, Brxe2x88x92, Ixe2x88x92, SO42xe2x88x92, SiO32xe2x88x92, CrO42xe2x88x92, BO32xe2x88x92, MnO4xe2x88x92, HGaO32xe2x88x92, HVO42xe2x88x92, ClO4xe2x88x92, BO32xe2x88x92, pillaring anions such as V10O28xe2x88x926 and MO7O246xe2x88x92, monocarboxylates such as acetate, dicarboxylates such as oxalate, alkyl sulphonates such as laurylsulphonate.
It should be noted that a variety of terms is used to describe the material which is referred to in this patent as an anionic clay. Hydrotalcite-like and layered double hydroxide are interchangeably used by those skilled in the art. In this patent application we refer to the materials as anionic clays, comprising within that term hydrotalcite-like and layered double hydroxide materials.
The most commonly described anionic clays are Mg-Al anionic clays. In the prior art the emphasis is usually on these types of anionic clays, whereas the Al-containing non-Mg anionic clays are only mentioned in passing, even though the chemistry of their preparation and their properties can be very different and unpredictable. Mg-Al anionic clays are suitable for many applications in the absorbent and catalysts field, but Al-containing non-Mg anionic clays have specific applications in these fields.
The preparation of anionic clays has been described in many prior art publications. Two major reviews of anionic clay chemistry were published in which the synthesis methods available for anionic clay synthesis have been summarized, F. Cavani et al xe2x80x9cHydrotalcite-type anionic clays: Preparation, Properties and Applications, xe2x80x9cCatalysis Todayxe2x80x9d, 11 (1991) Elsevier Science Publishers B. V. Amsterdam. J P Besse and others xe2x80x9cAnionic clays: trends in pillaring chemistry, its synthesis and microporous solidsxe2x80x9d(1992), 2, 108, editors: M. I. Occelli, H. E. Robson, Van Nostrand Reinhold, N.Y.
In these reviews basically two types of anionic clay preparation are described. The most conventional method is co-precipitation (in Besse this method is called the salt-base method) of a soluble divalent metal salt and a soluble trivalent metal salt, optionally followed by hydrothermal treatment or aging to increase the crystallite size. The second method is the salt-oxide method in which a divalent metal oxide is reacted at atmospheric pressure with a soluble trivalent metal salt, followed by aging under atmospheric pressure. This method has only been described for the use of ZnO and CuO in combination with soluble trivalent metal salts.
For work on anionic clays, reference is given to the following articles:
Helv. Chim. Acta, 25, 106-137 and 555-569 (1942)
J. Am. Ceram. Soc., 42, no. 3, 121 (1959)
Chemistry Letters (Japan), 843 (1973)
Clays and Clay Minerals, 23, 369 (1975)
Clays and Clay Minerals, 28, 50 (1980)
Clays and Clay Minerals, 34, 507 (1996)
Materials Chemistry and Physics, 14, 569 (1986).
In addition there is an extensive amount of patent literature on the use of anionic clays and processes for their preparation.
European Patent Application 0 536 879 describes a method for introducing pH-dependent anions into the clay. The clay is prepared by the addition of a solution of Al(NO3)3 and Mg(NO3)2 to a basic solution containing borate anions. The product is then filtered, washed repeatedly with water, and dried overnight. Additionally mixtures of Zn/Mg are used.
In U.S. Pat. No. 3,796,792 by Miyata et al. entitled xe2x80x9cComposite Metal Hydroxidesxe2x80x9d a range of materials is prepared into which an extensive range of cations is incorporated, including Sc, La, Th, In, etc. In the examples given solutions of the divalent and trivalent cations are prepared and mixed with base to cause co-precipitation. The resulting products are filtered, washed with water, and dried at 80xc2x0 C. Example 1 refers to Mg and Sb and Example 3 to Mg and Bi. Other examples are given, and in each case soluble salts are used to make solutions prior to precipitation of the anionic clay at high pH.
In U.S. Pat. No. 3,879,523 by Miyata entitled xe2x80x9cComposite Metal Hydroxidesxe2x80x9d also a large number of preparation examples is outlined. The underlying chemistry, however, is again based on the co-precipitation of soluble salts followed by washing and drying. It is important to emphasize that washing is a necessary part of such preparations, because to create a basic environment for co-precipitation of the metal ions a basic solution is needed and this is provided by NaOH/Na2CO3 solutions. Residual sodium, for example, can have a significant deleterious effect on the subsequent performance of the product as a catalyst or oxide support.
In U.S. Pat. No. 3,879,525 (Miyata) very similar procedures are again described.
In U.S. Pat. No. 4,351,814 to Miyata et al. a method for making fibrous hydrotalcites is described. Such materials differ in structure from the normal plate-like morphology. The synthesis again involves soluble salts. For example, an aqueous solution of a mixture of MgCl2 and CaCl2 is prepared and suitably aged. From this a needle-like product Mg2(OH)3Cl.4H2O precipitates. A separate solution of sodium aluminate is then reacted in an autoclave with the solid Mg2(OH)3Cl.4H2O and the product is again filtered, washed with water, and dried.
In U.S. Pat. No. 4,458,026 to Reichle, in which heat-treated anionic clays are described as catalysts for aldol condensation reactions, again use is made of magnesium and aluminum nitrate salt solutions. Such solutions being added to a second solution of NaOH and Na2CO3. After precipitation the slurry is filtered and washed twice with distilled water before drying at 125xc2x0 C.
In U.S. Pat. No. 4,656,156 to Misra the preparation of a novel absorbent based on mixing activated alumina and hydrotalcite is described. The hydrotalcite is made by reacting activated MgO (prepared by activating a magnesium compound such as magnesium carbonate or magnesium hydroxide) with aqueous solutions containing aluminate, carbonate and hydroxyl ions. As an example the solution is made from NaOH, Na2CO3 and Al2O3. In particular, the synthesis involves the use of industrial Bayer liquor as the source of Al. The resulting products are washed and filtered before drying at 105xc2x0 C.
In U.S. Pat. No. 4,904,457 to Misra a method is described for producing hydrotalcites in high yield by reacting activated magnesia with an aqueous solution containing aluminate, carbonate, and hydroxyl ions.
The methodology is repeated in U.S. Pat. No. 4,656,156.
In U.S. Pat. No. 5,507,980 to Kelkar et at al. a process is described for making novel catalysts, catalyst supports, and absorbers comprising synthetic hydrotalcite-like binders. The synthesis of the typical sheet hydrotalcite involves reacting pseudo-boehmite to which acetic acid has been added to peptize the pseudo-boehmite. This is then mixed with magnesia. More importantly, the patent summary states clearly that the invention uses mono carboxylic organic acids such as formic, propionic and isobutyric acid. In this patent the conventional approaches to preparing hydrotalcites are presented.
In U.S. Pat. No. 6,539,861 a process is disclosed for preparing a catalysts for synthesis gas production based on hydrotalcites. The method of preparation is again based, on the co-precipitation of soluble salts by mixing with base, for example, by the addition of a solution of RhCl3, Mg(NO3)2 and Al(NO3)3 to a solution of Na2CO3 and NaOH.
Also in U.S. Pat. No. 5,399,537 to Bhattacharyya in the preparation of nickel-containing catalysts based on hydrotalcite use is made of the co-precipitation of soluble magnesium and aluminum salts.
In U.S. Pat. No. 5,591,418 to Bhattacharyya a catalyst for removing sulfur oxides or nitrogen oxides from a gaseous mixture is made by calcining an anionic clay, said anionic clay having been prepared by co-precipitation of a solution of Mg(NO3)2, Al(NO3)3 and Ce(NO3)3. The product again is filtered and repeatedly washed with de-ionized water.
In U.S. Pat. No. 5,114,898/WO 9110505 Pinnavaia et al. describe layered double hydroxide sorbents for the removal of sulfur oxide(s) from flue gases, which layered double hydroxide is prepared by reacting a solution of Al and Mg nitrates or chlorides with a solution of NAOH and Na2CO3. In U.S. Pat. No. 5,079,203 /WO 9118670 layered double hydroxides intercalated with polyoxo anions are described, with the parent clay being made by co-precipitation techniques.
In U.S. Pat. No. 5,578,286 in the name of Alcoa a process for the preparation of meixnerite is described. Said meixnerite may be contacted with a dicarboxylate or polycarboxylate anion to form a hydrotalcite-like material.
In U.S. Pat. Nos. 4,946,581 and 4,952,382 to van Broekhoven co-precipitation of soluble salts such as Mg(NO3)2 and Al(NO3)3 with, and without the incorporation of rare earth salts was used for the preparation of anionic clays as catalyst components and additives. A variety of anions and di- and tri-valent cations are described.
U.S. Pat. No. 5,518,704 describes the preparation of a nickel-Al hydrotalcite prepared from peptized pseudoboehmite and nickel hydroxide.
As indicated in the description of the prior art given-above, there are many applications of anionic clays. These include but are not restricted to: catalysts, adsorbents, drilling muds, catalyst supports and carriers, extenders and applications in the medical field. In particular van Broekhoven has described their use in SOx abatement chemistry.
Because of this wide variety of large-scale commercial applications for these materials, new processes utilizing alternative inexpensive raw materials are needed to provide a more cost-effective and environmentally compatible processes for making anionic clays. In particular, from the prior art described above one can conclude that the preparation process can be improved in the following ways: the use of cheaper sources of reactants, processes for easier handling of the reactants, so that there is no need for washing or filtration, eliminating the filtration problems associated with these fine-particled materials, the avoidance of alkali metals (which can be particularly disadvantageous for certain catalytic applications): Further, in drying or calcining the anionic clay prepared by prior art processes gaseous emissions of nitrogen oxides, halogens, sulfur oxides, etc. are encountered which cause environmental pollution problems.
Our invention in its broadest embodiment comprises a process for the preparation of an aluminum-containing non-Mg anionic clay wherein a suspension comprising an aluminum source and a divalent metal source is provided and reacted, optionally under hydrothermal conditions, to obtain an aluminum-containing non-Mg-anionic clay, the aluminum source being aluminum trihydrate or its thermally treated form, and the divalent metal source not being a magnesium source.
Other objectives and embodiments of our invention encompass details about compositions, manufacturing steps, etc., all of which are hereinafter disclosed in the following discussion of each of the facets of the present invention.
This invention involves the preparation of Al-containing non-Mg anionic clays. In particular it describes a process for the preparation of an anionic clay wherein a suspension comprising an aluminum source and a divalent metal source is provided and reacted thermally or hydrothermally to obtain a Al-containing non-Mg anionic clay, the aluminum source being aluminum trihydrate or its thermally treated form.
The powder X-ray diffraction pattern (PXRD) of the product of the invention suggests that the product is comparable to anionic clays made by other standard methods. The physical and chemical properties of the product are also comparable to those anionic clays made by the other conventional methods. The overall process of this invention is very flexible, enabling a wide variety of anionic clay compositions and anionic clay-like materials involving for example carbonate, hydroxide and other anions to be prepared in an economically and environmental-friendly manner. The process may be carried out in a one-step process either in batch or in continuous mode.
It was found that Al-containing non-Mg anionic clays are directly obtained from the reaction according to the invention. This is in contrast to the coprecipitation method wherein soluble salts are first precipitated, filtered, washed to remove unwanted ions and then aged either hydrothermally or not. With the process according to the invention the presence of unwanted ions in the product can be avoided, as will be explained below.
The aluminum source is aluminum trihydrate or its thermally treated form. This alumina source is much less expensive than the usual aluminum sources such as aluminum salts or peptized boehmites. From this compound no ions beside hydroxide end up in the anionic clay, which is one of the normal building blocks of anionic clays. If for the divalent metal source a compound is chosen with harmless ions such as nitrate or acetate washing and filtration of the reaction product can be avoided altogether. In fact, it was found that the reaction also takes place when using hydroxides, oxides, hydroxycarbonates or carbonates for the divalent metal source in combination with the aluminum trihydrate or its thermally treated form, in which case also no washing and filtration has to take place.
Since the process disclosed in this patent does not require washing of the product or filtering, there is no filtrate waste or gaseous emissions (e.g. from acid decomposition), making the process particularly environmental-friendly and more suited to the environmental constraints which are increasingly imposed on commercial operations. The product can be spray dried directly to form microspheres or can be extruded, pelletized or beaded to form shaped bodies.
Anionic clays prepared by this method exhibit the well known properties and characteristics (e.g. chemical analysis, powder X-ray diffraction pattern, FTIR, thermal decomposition characteristics, surface area, pore volume, and pore size distribution) usually associated with anionic clays prepared by the customary and previously disclosed methods.
The anionic clay according to the invention has a layered structure corresponding to the general formula
[M(II)m2+Al(III)n3+(OH)2m+2n.]Xn/zzxe2x88x92.bH2O
Wherein m and n have a value such that m/n=I to 10, preferably 1 to 6, and b has a value in the range of from 0 to 10, generally a value of 2 to 6 and often a value of about 4. X may be CO32xe2x88x92, OHxe2x88x92 or any other anion normally present in the interlayers of anionic clays. It is more preferred that m/n should have a value of 2 to 4, more particularly a value close to 3.
The Trivalent Metal Source
In addition to the aluminum trihydrate or its thermally treated form which is the main trivalent metal source, other trivalent metal sources such as compounds containing Al3+, Mn3+, Fe3+, Co3+, Ni3+, Cr3+, Ga3+, B3+, trivalent rare earth metal cations such as La3+ and Ce3+, Ga3+ or mixtures of said compounds may be added. Preferably oxides, hydroxides and carbonates of these metals are used, but also nitrate chlorides, sulfates and phosphates can be used.
Divalent Metal Source
Suitable divalent metal sources are compounds containing Ca2+, Zn2+, Mn2+, Co2+, Mo2+, Ni2+, Fe2+, Sr2+, Ba2+, Cu2+, and mixtures of said compounds. Prefer oxides, hydroxides and carbonates of these metals are used, but also nitrates chlorides, sulfates and phosphates can be used.
Conditions
As mentioned above, the reaction is conducted under thermal or hydrothermal conditions. Within the context of this description hydrothermal means in the presence of water at at a temperture above 100xc2x0 C. at increased pressure. Thermal means at a temperature between ambient and 100xc2x0 C. Preferably the reaction takes place in water in an autoclave at a temperature above 100xc2x0 C., i.e. under autogeneous pressure.
It is possible to purge the suspension with nitrogen or inert gas if an anionic clay with predominantly hydroxide anions are desired, but in general this is not necessary. Thus, the reaction can be conducted in the presence of CO2. Said CO2 may be the CO2 normally present in air or it may be added to the reaction, for instance, by using a carbonate divalent or trivalent metal source.
Said aqueous suspension may be obtained by either combining slurries of the starting materials or adding divalent metal source to a slurry of trivalent metal source or vice versa. There is no need to wash or filter the product, as unwanted ions (e.g. sodium, ammonium, chloride, sulfate) which are frequently encountered when using other preparation methods, are absent in the product. If desired a preformed anionic clay may be added to the reaction mixture. Said preformed clay may be recycled anionic clay from the reaction mixture or anionic clay made separately by the process according to the invention or any other process.
xe2x80x9cBecause of its simplicity, this process can be carried out in a continuous mode.xe2x80x9d
As mentioned-above, if desired inorganic acids and bases, for example for control of the pH, may be added to the slurry before or during reaction or to the individual reactants before combining them in the slurry. The acid and bases of choice are formic acid, acetic acid, nitric acid and ammonium hydroxide, because these types of acids and bases do not introduce unwanted ions in the reaction mixture.
The most preferred combinations of divalent metal sources and Al sources are Alxe2x80x94Zn, and Alxe2x80x94Cu, because these combinations result in Al-containing non-Mg anionic clays with specific applications in the catalyst field.
If desired, the anionic clay prepared by the process according to the invention may be subjected to ion exchange. Upon ion exchange the interlayer charge-balancing anions are replaced with other anions. Said other anions are the ones commonly present in anionic clays and include pillaring anions such as V10O28xe2x88x926, Mo7O246xe2x88x92. Said ion exchange can be conducted before drying or after the anionic clay formed in the slurry.
The process of the invention provides wide flexibility in preparing products with a wide range of M(II):Al(III) ratios. The M(II):Al(III) ratio can vary from 0.1 to 10, preferably from 1 to 6, more preferred from 2 to 4, and especially preferred to close to 3.
For some applications it is desirable to have additives, both metals and nonmetals, such as rare earth metals, Si, P, B, group VI, group VIII, alkaline earth (for instance Ca and Ba) and/or transition metals (for example Mn, Fe, Co, Ti, Zr, Cu, Ni, Zn, Mo, Sn), present. Said metals can easily be deposited on the anionic clay. They can also be added either to the divalent metal source or the trivalent metal source or to the slurry during preparation of the anionic clay.

Process for producing Al-containing non-Mg-anionic clay


A device for suctioning material from skin pores, the device having a tip member, an elongated grip body having at least a transparent section, and a filter cartridge having at least a transparent section, with a filter disposed within the filter cartridge which allows passage of air but blocks passage of material, such that material extracted from the skin pores is observable as it passes through the grip body and is visible on the surface of the filter.

This invention relates generally to the field of devices which are used to clean or remove material from skin pores, such as sebum residues, dirt, bacteria, whiteheads, blackheads, etc., and more particularly the invention relates to such devices which utilize suction to accomplish the task.
When materials become trapped within skin pores, whether internally produced such as sebum or externally contacted such as dirt or bacteria, the natural flow of the pore is blocked and undesirable skin blemishes or conditions develop, such as pimples, white heads or blackheads, also known as comedomes, or acne. In order to relieve the problem, the skin pores must be cleared of the undesirable materials so that the natural expulsion process of the pore is restored and so that medication can be received by the pore.
A well known methodology for addressing this problem is through the use of suction devices which have relatively small suction tips. The tip is pressed against the pore and a vacuum is produced within the device, the internal vacuum extracting the material from within the pore and into the device. An early example of this type of device is shown in U.S. Pat. No. 2,267,636 to Benton, wherein a spring-biased plunger arrangement is provided. The tip of the apparatus is applied to the pore to be cleaned and the internal plunger is retracted to create suction through the tip, drawing the material into the device. The material is later expelled from the device by moving the plunger forward. Because mechanical manipulation of the device is required for its operation and because the suction effect is non-continuous, the efficiency of the device is relatively limited, since improper placement or movement of the tip during the retraction operation may fail to remove the material from the pore, necessitating multiple attempts to cleanse a single pore. To solve this problem, devices have been developed which utilize a continuous suction, produced mechanically by vacuum pumps or through liquid flow suction systems. For example, Naibert in U.S. Pat. No. 1,732,310 and Brenner in U.S. Pat. No. 3,794,035 show skin suction devices which utilize mechanical means to create a continuous suction through a nozzle pressed against the skin. Schatz in U.S. Pat. No. 5,624,416 shows a suction device which includes a pinching jaw at the distal tip, where the partial vacuum is created by connecting a conduit to a water flow in a manner whereby the water flow creates a partial vacuum in the conduit. Fields er al. in U.S. Pat. No. 6,019,749 shows a suction device where a first suction means is used to draw the skin around the pore outward and a section suction means, internal to the first, is used to draw the material from the pore.
It is an object of this invention to provide a pore cleaning device which utilizes suction to extract material from within the skin pore, the device being an improvement over the known devices used to accomplish this task. To this end, it is a further object to provide such a device which is hand-held and which is operationally simple. It is a further object to provide such a device where the main housing is an elongated tube for easy grasping by the operator, where the tips are removable from the housing, and where a filter is provided to collect the material removed from the pores. It is a further object to provide such a device which provides a visual indication to the operator that the device is properly functioning, as well as a visual indicator of the amount of material removed from successive pores, which is accomplished by composing the elongated tube portion and the filter housing from transparent material.
The invention is in general a device for removing material, such as for example sebum deposits, dirt, bacteria, blackheads, whiteheads, etc., from skin pores by suctioning the material from the pores. The invention comprises in general a hand-held body of elongated shape, the body being tubular and adapted to receive and retain a tip member on its distal end. The tip member has a distal nozzle and a bore of relatively small diameter, the tip bore communicating with the bore of the body. A filter means is disposed either within the body or within a filter cartridge housing connected in communicating manner with the body. Suction means are provided to create a partial vacuum within the device, such that material is drawn from the skin pores through the tip member and the body, where it is entrapped by the filter. At least a portion of the body, and at least a portion of the separate filter cartridge if present, on the upstream side of the filter is formed of a transparent material so that the filter is exposed and so that the operator can monitor the efficacy of the device during use, as well as providing visual evidence of the amount and type of material removed by the device. The tip member may be removable, such that disposable tip members can be used.

Suction device for removing material from skin pores


The method of selecting and implanting a permanent venous catheter into a patient for use in chronic, extracorporeal blood treatment procedures. The method comprises determining the Body Surface Area of the patient. One then selects a permanent venous catheter having an actual length which is within 10% of a desired length as indicated in a Table found in this application for the Body Surface Area of the particular patient and a particular vein through which the catheter is to extend. Also, the internal diameter of the tubing is preferably adjusted in a manner correlating with the catheter length. Following catheter selection, the venous catheter is implanted in the venous system of the patient with the distal tip of the catheter being in or adjacent to the upper right atrium of the heart.

Jugular and subclavian catheters are intended as a permanent blood access for fluid delivery into the blood stream or egress of blood. Although these catheters may be used for various purposes including treatment of acute renal failure, they are essentially intended for treatment of chronic renal failure. The invention will decrease the rates of thrombosis and infections and prolong the overall survival of the catheters.
There are numerous manufacturers producing various implantable catheters, and the line of products is changing every year. An extensive review of all available catheters for acute and chronic hemodialysis was published in 1995 (Twardowski ZJ: Percutaneous blood access for hemodialysis. Seminars in Dialysis 1995; 8: 175-186).
Dual Lumen Catheters
These catheters are made of silicone rubber or polyurethane. Silicone rubber is less thrombogenic than polyurethane. Polyurethane is thermoplastic, while silicone rubber is thermoset and does not soften at body temperature. Depending on the manufacturing process, the silicone rubber catheter may be made softer or harder, but is usually made soft. Most currently used catheters have dual lumens and are provided with a single polyester cuff. Most dual-lumen catheters have a beveled inflow bore and a few side holes for inflow. Almost all catheters are radiopaque or are provided with radiopaque stripe.
The catheters are inserted transcutaneously through the subclavian or jugular veins using a peel-away sheath method or surgically through the jugular vein into the superior vena cava or right atrium. Femoral veins are usually not used as a long-term access for hemodialysis. Jugular veins serve as a primary insertion site, because complication rates associated with insertion through the subclavian veins are significantly higher.
Although historically the catheters were inserted with various approaches, currently the catheter is usually inserted through the Sedillot triangle (between the sternal and clavicular heads of the sternocleidomastoid muscle) using the Seldinger (Seldinger SI: Catheter replacement of needle in percutaneous arteriography; new technique. Acta Radiol 1953; 39: 368-376) method. In this method the vein is punctured with a large bore needle and a guide wire is inserted into the vein through the needle. The needle is withdrawn, the skin tunnel is created by a small incision, the entrance into the vein is prepared by a dilator. The subcutaneous tunnel is created with a trocar, the catheter is inserted through the tunnel and introduced into the vein using peel-away sheath. Then the tip of the catheter is advanced through the brachiocephalic vein into the superior vena cava or right atrium. The surgical method is similar, with the exception that the incision over the Sxc3xa9dillot triangle is bigger and the vein is punctured under the direct vision.
There are two method of subcutaneous tunnel creation. Because most catheters have an attached Y extension for connection with the dialyzer lines, the tunnel must be created from the skin exit to the site of the vein puncture (standard tunneling method). Another method, as described in my previous patents (U.S. Pat. Nos. 5,209,723; 5,405,320; and 5,509,897) requires that the catheter be tunneled from the vein puncture site to the exit (reversed tunneling method). Such a method is possible if the Y extension is attached to the catheter after the catheter is pulled through the exit. In both methods the subcutaneous tunnel is created over the clavicle; thus the catheter in the tunnel has more or less a reversed xe2x80x9cUxe2x80x9d shape.
Mutatis mutandis, an insertion through the subclavian veins is similar to that through the jugular veins. The puncture ofthe subclavian vein is done just below the clavicle and slightly outside of the midclavicular line.
To prevent blood recirculation, most dual lumen catheters have inflow and outflow bores staggered approximately 2 cm, with outflow bore distal to that of inflow bore. Our studies (Twardowski Z J, Van Stone J C, Haynie J: All currently used measurements of recirculation in blood access by chemical methods are flawed due to intradialytic disequilibrium and/or recirculation at low flow Am J Kidney Dis 1998; 32 (6): 1046-1058.) showed that at the high blood flow (over 300 mL/min) blood recirculation is only moderate, even in catheters with a flush tip. Various tip configurations aiming at decreasing clot formation were patented (U.S. Pat. No. 5,509,897; 5,569,182; and 5,685,867).
Single Lumen Catheters
For subclavian vein catheterization, single lumen catheters were used in 1969 (Erben J, Kvasnicka J, Bastecky J, Vortel V: Experience with routine use of subclavian vein cannulation in haemodialysis. Proc Eur Dial Transpl Assoc 1969; 6: 59-64), a long time before two lumen catheters were invented. Canaud et al.(Canaud B, Bxc3xa9raud J J, Joyeux H, Mion C: Internal jugular vein cannulation using 2 silicone rubber catheters: A new, simple and safe long-term access for extracorporeal treatment. Nephron 1986; 43: 133-138. Canaud B, Bxc3xa9raud J J, Joyeux H, Mion C: Internal jugular vein cannulation with two silicone rubber catheters: a new and safe temporary vascular access for hemodialysis: Thirty months"" experience. Artif Organs 1986; 10: 397-403.) decided to continue the method of Erben et al. using two single-lumen catheters, but they changed material from polyethylene to silicone rubber and used jugular instead of subclavian vein insertion site. The catheters with inner/outer diameters of 2.0/3.2 mm had 6 side holes on the 5 distal centimeters. The catheters were exteriorized by reversed tunneling (from the cervical incision to the skin exit), and extension-tubing adapters were attached to the catheters after their externalization. The catheters were not provided with cuffs.
An important advantage of single catheters is its smaller entrance into the vein and smaller exit site. With the smaller entrance it is more likely to be able to cannulate the vessel repeatedly. The smaller exit is less prone to infections; however, infections were the most common complications of long-term jugular vein catheters (Canaud B. Leray H. Bxc3xa9raud J J. Mion C. Acces vasculaire temporaire: du peripherique au central, du temporaire au permanent. [Temporary vascular access: from peripheral to central, from temporary to permanent]. Nephrologie. 1994; 15: 53xe2x80x949.). It is worth stressing that these catheters were not provided with cuffs.
Single lumen catheters for single needle dialysis were developed in the late 1980""s. A regular, Tenckhoff peritoneal dialysis catheter was used by Liggett et al. (Liggett R A, Kearney M M: Tenckhoff catheter as a primary hemodialysis vascular access. Dialysis and Transplantation,1988; 17: 522-524, 546.) Thrombotic complications of this catheter were frequent as an anticoagulant was leached out of the tip through side holes. A single, silicone rubber catheter with fish-mouth tip to prevent sucking against the vessel wall was developed by Bionic Company (Friedrichsdorf, Germany) and the results with this catheter were reported by Demers et al. (Demers H G, Siebold G, Schielke D J, Mueller W, Niemeyer R, Hoeffler D: Soft right atrial catheter for temporary or permanent vascular access. Dialysis and Transplantation, 1989; 18: 130-139.) The catheter had a single polyester cuff as a barrier to periluminal bacterial penetration, and no side holes at the tip to avoid sucking of the intima and/or leaching out of anticoagulant.
Tesio et al. (Tesio F. De Baz H. Panarello G. Calianno G. Quaia P. Raimondi A. Schinella D. Double catheterization of the internal jugular vein for hemodialysis: indications, techniques, and clinical results. Artif Organs. 1994; 18 :301xe2x80x944.) used catheters very similar to those of Canaud. These were silicone rubber catheters with internal/external diameters of2.0/3.2 mm and provided with 6 side holes on the 4 distal cm. Unlike Canaud catheters, Tesio catheters were provided with a 1 cm olive-like device to better fix the cannula in the tunnel. A recent model of Tesio catheter is provided with a small cuff (2 mm wide) located on the olive-shape device. Tesio et al. (Tesio F, De Baz H, Panarello G. Successful Long-term Central Venous Access. Home Hemo Int. 1998; 2: 38-40) describe lower infection rates than that reported by Canaud et al.
Hybrid of Single and Double Lumen Catheter
A hybrid of single and dual lumen catheters, the Ash Split Cathwas recently developed by Ash and his colleagues. The intravenous segment is composed of two separate D-shaped lumens, which have multiholed cylindrical tips (Mankus R A. Ash S R. Sutton J M: Comparison of blood flow rates and hydraulic resistance between the Mahurkar catheter, the Tesio twin catheter, and the Ash Split Cath. ASAIO Journal. 1998; 44: M532-4). The transcutaneous portion is a 14 French cylindrically shaped catheter with D-shaped lumens and a polyester cuff. The cylindrical transcutaneous part extends externally and connects through a hub with two transparent lumens attached to Luer lock Whereas the extravascular part and the entrance to the vessel is similar in shape and function to dual lumen catheters, the intravascular part is similar to single lumen catheters. The catheter is inserted with a single vein puncture. Two lumens in the vessel may have advantage over dual lumen by being more flexible.
Hybrids of Subcutaneous and Percutaneous Devices
Two new devices that are hybrids of percutaneous and subcutaneous devices were developed by Biolink Corporation (Middleboro, Mass.) and VascA (Topsfield, Mass.). The first device (Dialock(trademark) Hemodialysis Access System) consists of a port-like valve, implanted subcutaneously below the clavicle, which is connected to two single lumen catheters implanted into the right atrium (Canaud B, My H, Morena M, Lamy-Lacavalerie B, Leray-Moragues H, Bosc J Y, Flavier J L, Chomel P Y, Polaschegg H D, Prosl F R, Megerman J. Dialock: a new vascular access device for extracorporeal renal replacement therapy. Preliminary clinical results. Nephrol Dial Transplant 1999; 14(3):692-8). For each hemodialysis the port is accessed with needle-cannulas, one for inflow, the other for outflow. After dialysis the cannulas are removed and the whole device remains subcutaneously. The second device (LifeSite(copyright) Hemodialysis Access System) consists of two subcutaneous valves with an internal pinch clamp that is actuated with a standard 14-gauge dialysis needle, each connected to a single lumen cannula placed in the central venous circulation for hemodialysis. One valve with attached cannula is for blood inflow and the other is for blood outflow (Beathard G A, Posen G A Initial clinical results with the LifeSite(copyright) hemodialysis access system. Kidney Int. 2000 Nov;58(5):2221-7). The devices share the advantages and disadvantages of both, subcutaneous and percutaneous blood accesses for hemodialysis.
Complications of Intravenous Catheters
There are two major complications of intravenous catheters: infection and thrombosis. Both are at least partly related to the catheter design.
Infections
There may be exit site/tunnel infection, sepsis, and septic thrombophlebitis.
Measures Preventing Infections
Infection rates may be decreased by catheter design, implantation technique and postimplantation care. Here I will concentrate on catheter features decreasing complications.
Material
Silicone rubber is a preferred material, because of its softness and hydrophobic (water repellant) properties.
Tunnel Length
The length of the tunnel is dependent on the catheter length outside of the vein. The longer the tunnel the less likely it is for the microorganism to penetrate into the blood stream, but in a randomized prospective study, tunneling alone of uncuffed catheters was not found to decrease sepsis rates (von Meyenfeldt M M. Stapert J. de Jong P C. Soeters P B. Wesdorp R I. Greep J M. TPN catheter sepsis: lack of effect of subcutaneous tunneling of PVC catheters on sepsis rate. Jpen: J Parenter Enteral Nutr 1980; 4:514-7). On the other hand the tunnel cannot be too long, so that the exit would not be too low on the chest.
Cuffs
The cuff constitutes a significant barrier for periluminal bacterial penetration and the infection rates with the cuffed catheters are markedly lower than that with uncuffed catheters. There is no question that catheters without cuffs, both intravenous and peritoneal, are associated with very high infection rates and are not suitable for chronic use. Catheter related sepsis was found to be more than ten times higher with uncuffed catheters as compared to cuffed catheters in pediatric population (Rovner M S, Brouhard B H, Cunningham J, Firor H: Comparison of cuffed vs. uncuffed catheters for extracorporeal therapy in pediatric patients. Dialysis and Transplantation 1992; 21: 513-522) Although there are no data on the relationship between the number of cuffs and periluminal infection rates with intravenous catheter, such data exist for peritoneal catheters. A recent publication of the United States Renal Data System reported that compared to double-cuff catheter the risk of peritonitis was 16 and 31% higher for single deep-cuff and single superficial-cuff catheters respectively. (U. S. Renal Data System, USRDS 1992 Annual Data Report, VI. Catheter-Related Factors and Peritonitis Risk in CAPD Patients. Am J Kidney Dis 1992; 5 (Suppl 2): 48-54). Our own study found that the peritonitis rates were lower with triple cuffed catheters compared to the double cuffed catheters (Twardowski Z J, Prowant B F, Nichols W K, Nolph K D, Khanna R: Six-year experience with swan neck catheter. Perit Dial Int 1992; 12:384-389). Exit site infections were also found to be lower with cuffed catheters. Rovner et al. (Rovner M S, Brouhard B H, Cunningham J, Firor H: Comparison of cuffed vs. uncuffed catheters for extracorporeal therapy in pediatric patients. Dial Transplant 1992; 21: 513-522) reported an exit infection rate of 1.26/1000 days, with cuffed catheters compared with a rate of 4.85/1000 days with uncuffed catheters. The reason for higher infection rates with the absence of a cuff is poor immobilization of the catheter that permits catheter movement outside the sinus where it collects contaminants and transfers them deep into the sinus after retraction. Also, catheter movement to and fro in the subcutaneous tunnel causes microtraumas predisposing further to infections.
Lumen Lock
Between hemodialysis sessions, it is customary to lock catheter lumens with anticoagulant to prevent clot formation. Four anticoagulants have been used: heparin, urokinase, tissue plasminogen activator, and sodium citrate. Recently the locking solution has been provided also with antibacterial properties. For this purpose an anticoagulant has been mixed with the antibiotic (Boorgu R, Dubrow A J, Levin N W, My H, Canaud B J, Lentino J R, Wentworth D W, Hatch D A, Megerman J, Prosl F R, Gandhi V C, Ing T S. Adjunctive antibiotic/anticoagulant lock therapy in the treatment of bacteremia associated with the use of a subcutaneously implanted hemodialysis access device. ASAIO J. 2000;46(6):767-70.) No incompatibility was found in tests in vitro if heparin in final concentration of 5,000 U/mL was mixed with vancomycin, ceftazidime, cefazolin, or gentamicin (Vercaigne L M, Sitar D S, Penner S B, Bernstein K, Wang G Q, Burczynski F J. Antibiotic-heparin lock: in vitro antibiotic stability combined with heparin in a central venous catheter. Pharmacotherapy 2000;20(4):394-9.) If this method is used concomitantly with systemic antibiotics for treatment of catheter related bacteremia, the method gives positive results without catheter removal in the majority of cases (Capdevila J A. Catheter-related infection: an update on diagnosis, treatment, and prevention. Int J Infect Dis. 2(4):230-6, 1998. xe2x80x94Sodemann K, Lubrich-Birkner I, Berger O, Baumert J, Feldmer B, von Hodenberg E. Gentamicin/sodium-citrate mixture as antibiotic-lock technique for salvage and prevention of catheter-related infectionsxe2x80x94A four year trial (abstract). J Am Soc Nephrol 8:173A, 1997.
Thrombosis
As early as in the mid 19th century, Rudolf Virchow postulated that three factors predispose to phlebothrombosis (clot formation in the vein): hypercoagulable state, vein wall damage, and blood stasis. These three factors are still judged to be the most important, and have to be considered in planning preventive measures. With a foreign body in the blood vessel, an additional factor becomes important: the material from which this foreign body is made.
Measures Preventing Thrombosis
Thrombosis probably cannot be completely eliminated, but its incidence may be reduced by catheter design and appropriate anticoagulation. Only catheter design features decreasing thrombosis rates will be discussed here. These are: material, catheter shape and size, tip configuration, and number of lumens.
Material
Thrombogenicity of material is crucial in the speed of thrombus formation. Due to high thrombogenicity, prolonged catheterization was impossible with glass, polyethylene and polyvinyl cannulae. Polyurethane is claimed to be less thrombogenic than tetrafluoroethylene. In animal studies, silicone rubber catheters showed the lowest thrombogenicity compared to catheters made of other materials (Welch G W, McKell D W, Silverstein P, Walker H L: The role of catheter composition in the development of thrombophlebitis. Surg Gynecol Obstet 1974; 138: 421-442). Silicone rubber is a preferred material to prevent catheter-related thrombosis.
Insertion Site
The repeated damage to the intima seems to be crucial in thrombosis of cannulated veins. A strong argument for this mechanism is more frequent and massive thrombosis seen with left sided cannulation where the vein path is more tortuous (Ratcliffe P J, Oliver D O: Massive thrombosis around subclavian cannulas used for haemodialysis (Letter). Lancet 1982; 1: 1472-1473). In the series of Hoshal et al. (Hoshal V L Jr, Ause R G, Hoskins P A: Fibrin sleeve formation on indwelling subclavian central venous catheters. Arch Surg 1971; 102: 353-358) mural thrombi usually formed at the points where the catheter pressed on the vessel wall, particularly where the tip touched on the intima. In choosing the insertion site these factors should be borne in mind. The jugular route, particularly on the right side, is advantageous since the course of catheter to the right atrium is almost a straight line, minimizing trauma to the intima. The path from the left jugular vein is more tortuous. Subclavian veins are least favorable because of tortuous course, particularly on the left side. Besides, the narrow space between the first rib and the clavicle, where the subclavian vein passes, predisposes to vein wall trauma when movement of the upper extremities squeezes the catheter. Cimochowski et al (Cimochowski G E, Worley E, Rutherford W E, Sartain J, Blondin J, Harter H: Superiority of the internal jugular over the subclavian access for temporary dialysis. Nephron, 1990; 54: 154-161) stressed that vein stenosis is least likely if the stiff catheter is inserted through the right jugular vein. Schillinger et al. (Schillinger F, Schillinger D, Montagnac R, Milcent T: Post catheterisation vein stenosis inhaemodialysis: Comparative angiographic study of 50 subclavian and 50 internal jugular accesses. Nephrol Dial Transplant, 1991; 6: 722-724) evaluated phlebographically the rate of stenosis of the subclavian and/or brachiocephalic vein in cases cannulated previously through the subclavian route or through the jugular route. They found a stenosis in 42% of the subclavian group and in 10% of the jugular group. The right side was cannulated in 58% of cases in the subclavian group and 78% in the jugular group. The rate of stenosis on the left side was higher, particularly in the jugular group (7.7% on the right and 18.2% on the left). It is worth stressing that the authors described the complications with use of stiff catheters.
Side Holes at the Distal End
All catheters for acute hemodialysis are provided with side holes at the distal end. This is supposed to prolong catheter life, assuming that even if the distal bore is occluded by a clot, a few side holes may remain opened providing sufficient blood flow. Most catheters for chronic dialysis, both single and dual lumen, are also provided with side holes. There are no data in support of the notion that side holes prolong the life of chronic catheters. In my opinion the opposite may be true. Firstly, many times, while removing chronic catheters, either electively or because of catheter obstruction, a clot is found attached to the tip of the catheter and anchored in the side hole of the inflow lumen. Such a clot is difficult to remove or dissolve while in situ. Secondly, intraluminal clot is usually easily removed or dissolved (Twardowski Z J: High-dose intradialytic urokinase to restore the patency of permanent central vein hemodialysis catheters. AJKD 1998; 31 (5): 841-847). The clot, which is difficult to remove is formed on the outer surface of the catheter and extends to the inside lumen. If so, the holes have no role in extending the life of the catheter. Thirdly, the heparin solution, which is instilled to the catheter lumen at the end of dialysis, may not reach the catheter tip and/or be leached out in the period between dialyses, thus, predisposing to clot formation at the tip of the inflow lumen. Finally, if the inflow bore is occluded and the blood flows through the side holes, it is likely that the vein intima is sucked into the holes, becomes damaged and causes formation of the clot in the vessel lumen. In such a case these holes would not be beneficial for the catheter life, but maybe even precluding the possibility of inserting another catheter into the same vein at a later time. (Twardowski Z J, Moore H L Side holes at the tip of chronic hemodialysis catheters are harmful. Journal of Vascular Access 2001; 2(1): 8-16).
Shape of the Catheter
It is very likely that the major reason of these complications is pressure of the straight catheter on the vein intima at the xe2x80x9cpressure pointsxe2x80x9d where venous path takes a rapid turn. This led us to design a so-called xe2x80x9cvein shape cathetersxe2x80x9d, which has been patented (U.S. Pat. Nos. 5,209,723; 5,405,320; 5,509,897; 5,569,182; and 5,685,867). The idea of these catheters is to make the shape of the catheter as similar as possible to the shape of vein where the catheter is located; however, it is difficult to choose the catheter with the shape similar to that of the vein.
Size of the Catheter
Companies manufacturing catheters make them in a few sizes. For instance, Kendall Healthcare (Mansfield, Mass.) makes three sizes of PermCath straight catheters: 36 cm, 40 cm, and 45 cm. The length of the catheter is a total length, from the tip to the luer lock end. BARD (Salt Lake City, Utah) makes three sizes of permanently bent catheters: 19 cm, 23 cm, and 27 cm. The length of the catheter is from the tip to the cuff. The catheters of the same type have the same internal diameter, regardless of their length. This practice causes that the shorter catheters have higher blood flow at the same inflow pressure than the longer catheters.
This approach has disadvantage, as longer catheters, inserted in patients with larger body build, should have higher blood flow to achieve a desired efficiency of dialysis. According to the Dialysis Outcome Quality Initiative (DOQI) recommendations, all patients should have delivered Kt/V of 1.2-1.3. (NKF-DOQI clinical practice guidelines for hemodialysis adequacy. National Kidney Foundation. Am J Kidney Dis. 1997; 30(3 Suppl 2):S15-66.) Kt/V is a product of dialyzer clearance multiplied by time of dialysis and divided by volume of distribution of urea or total body water. Total body water is roughly proportional to the body height and weight (Watson P E, Watson I D, Batt R D. Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr. 1980;33(1):27-39.) and clearance is proportional to the blood flow within certain limits depending on the dialyzer mass transfer area coefficient. Thus, to satisfy DOQI requirements, longer catheters, inserted into larger patients, should have higher, not lower, blood flow.
Poiseuille""s equation predicts that, in circular tubes, at the same pressure difference and catheter length, the laminar flow is proportional to the 4th power of the radius. On the other hand, the catheter diameter cannot be too large to fill the vein too tightly as it predisposes to the damage of vein wall, vein thrombosis and stenosis [Dixit A, Ram S, Zaman F, Pervez A, Torres C, Work J. Does the Ash split catheter have a better survival than the Mahurkar catheter? J Am Soc Nephrol 10: abstract A1042, 1999, Davenport A. Central venous catheters for hemodialysis: How to overcome the problems. Hemodial Int 4:78-82, 2000.] The availability of only a few sizes of the catheters create a problem of locating the catheter tip in an appropriate point in patients of different body builds. Most catheters have internal diameter of 2 mm (PermCathxe2x80x94Kendall Healthcare, Opti-flow (BARD), Tesioxe2x80x94MedComp, Harleysville, Pa.) or 2.2 mm (Dialockxe2x80x94Biolink Corporation, LifeSitexe2x80x94VascA) regardless of catheter length.
For the best performance the tip of a central vein catheter for hemodialysis should be located in the right cardiac cavities [Jean G, Chazot C, Vanel T, Charra B, Terrat J C, Calemard E, Laurent G. Central venous catheters for hemodialysis: looking for optimal blood flow. Nephrol Dial Transplant 12(8):1689-91, 1997]. Schwab and Beathard recommend catheter tip localization in the middle of the right atrium, while the patient is supine, so it will move no higher than to the lower superior vena cava while the patient is upright [Schwab S J, Beathard G. The Hemodialysis Catheter Conundrum: Hate Living with Them, But Can""t Live Without Them.] (Kidney Int. 1999; 56: 1-17). Both too high and too low positions of the catheter tip are unfavorable. The heart moves down in the upright position and up in the supine position. Because the catheter length is fixed, the catheter moves deeper into the right atrium, while the patient is supine, and closer to the brachial veins, while the patient is upright. Breathing also influences catheter position. During deep inspiration the diaphragm and the heart move down so the catheter tip moves up; during expiration the movements are in opposite directions. Finally, the chest wall subcutaneous tissue moves down when the supine person assumes the erect posture (Schwab S J, Beathard G. ibid) The catheter cuff, which is anchored in this tissue, pulls the catheter tip upward.
If the catheter tip is located high in the superior vena cava it may translocate to one of the brachiocephalic veins where the blood flow is insufficient to secure adequate blood flow through the dialyzer. If the catheter tip is too low it may move to a cusp of the thebesian or eustachian valve, or migrate to the inferior vena cava or to the right ventricle. All this positions are unfavorable for catheter function. The catheter tip in the inferior vena cava gives apparently paradoxical low recirculation values with reversed lines (Twardowski Z J, Nichols W K, Van Stone J C, Haynie J: All currently used measurements of recirculation in blood access by chemical methods are flawed due to intradialytic disequilibrium or recirculation at low flow. Am J Kidney Dis 32 (6): 1046-1058, 1998.) and provides high recirculation values with standard direction of lines. If catheter migrates to the right ventricle, it may become entangled in the papillary muscles and become obstructed (Twardowski Z J: Nichols W K: Opti-flow catheter tip translocation from the right atrium to the right ventricle. Journal of Vascular Access 2001; 2(1): 17-19. Too low position of the catheter tip in the right atrium predisposes to formation of the right atrial thrombus ([Gilon D, Schechter D, Rein A J, Gimmon Z, Or R, Rozenman Y, Slavin S, Gotsman M S, Nagler A. Right atrial thrombi are related to indwelling central venous catheter position: insights into time course and possible mechanism of formation. Am Heart J. 135(3):457-62, 1998. Korones D N, Buzzard C J, Asselin B L, Harris J P. Right atrial thrombi in children with cancer and indwelling catheters. J Pediatr 128(6):841-6, 1996). All these problems require that a catheter length be precisely selected for a patient. I believe that the best compromise between conflicting requirements is to locate the catheter tip in the upper right atrium (URA).
Optimal Lengths and Diameters of Catheters
A study in 31 volunteers of large upper body veins using magnetic resonance imaging showed a great variability in vein dimensions and shapes even in persons with the same body build. (Twardowski, Z J and Seger R M: Dimensions of central venous structures in humans measured in vivo using magnetic resonance imaging: Implications for central vein catheter dimensions The International Journal of Artificial Organs, Vol. 25, 2, 2002, pp. 107-123). In this study, the shapes and distances from the insertion sites in jugular and subclavian veins to the right atrium were determined and correlated with the height, acromion-distance, weight, body surface area, and combinations thereof.
The tip of the dual lumen, straight catheters such as VasCath(trademark) (BARD, Salt Lake City, Utah, USA) or PermCath(copyright) (Kendall Healthcare, Mansfield, Mass., USA) may be properly positioned, if x-ray is used during catheter implantation. Because straight catheters are prone to kinking after implantation, the manufacturers supplemented these catheters with permanently bent catheters: Opti-Flow(trademark) (BARD, Salt Lake City, Utah) or Swan Neck(trademark) PermCath(trademark) (Kendall Healthcare, Mansfield, Mass.). If these catheters are inserted through an internal jugular vein, the bend is located over the clavicle. Although insertion through the internal jugular vein is preferred, the catheters may be inserted through the subclavian veins. In these cases the bend is located below the clavicle. The length from the bend to the tip is essentially fixed; therefore the catheter length should be selected for the patient. If there is no guidance as to the appropriate length of the bent catheter, the catheter tip maybe located too high or too low. For this purpose, the exact dimensions of the venous system in vivo should be known; otherwise the catheter selection would be based on guessing and the tip may translocate later to the improper position (Twardowski Z J: Nichols, W K: Opti-flow catheter tip translocation from the right atrium to the right ventricle. Ibid.
A perfect position of the tip of the bent catheter could be achieved if magnetic resonance image were performed in a patient before catheter implantation and the precise measurements were performed as described in the methods section of the magnetic resonance imaging study [Twardowski Z J and Seger R M: Dimensions of central venous structures in humans measured in vivo using magnetic resonance imaging: Implications for central vein catheter dimensionsxe2x80x94unpublished, manuscript attached]. Another approach would be to implant a catheter basing the selection on guessing and replace for another if the guess was wrong. Both approaches, however, would be costly and impractical. It is much more convenient for the operator to know the optimal choice of the catheter length before the procedure. The ranges of vein dimensions with the same body size are considerable. Fortunately the acceptable position of the catheter tip ranges from the middle of the right atrium to the lower superior vena cava and the selection of a catheter guided by our study will usually be adequate. The most practical and effective approach to the selection of the appropriate catheter length is to take into account body surface area of the patient.
Accordingly, there is a need to determine for an individual patient a precise optimum catheter length and inner diameter that would best suit the patient as a permanent, implantable catheter. When optimum catheter dimensions are provided to the patient, the tip of the catheter will more reliably stay in the upper right atrium, so that the catheter will function better. Also, thrombosis rates can be decreased, and the overall catheter survival increased, by the selection and provision of a properly sized catheter for the patient. Surprisingly, the desired length, and consequently the desired internal diameter of catheters, strongly correlate with the body surface area of the patient. In other words, a short, stocky patient and a tall, thin patient may have similar body surface areas, and, surprisingly, may have optimum catheter lengths for a particular implantation that are similar.
In accordance with this invention, a method is provided for selecting and implanting a permanent, venous catheter into a patient for use in chronic extracorporeal blood treatment procedures. The steps of the method comprise:
1. Determining the body surface area (BSA) of the patient. This is a known medical procedure, and it maybe determined in customary manner, to preferably obtain the body surface area in square meters.
2. One then selects a permanent venous catheter having an actual length from the catheter distal tip to its integral, proximal end which is within 10% of a desired length, typically in cm, as indicated in Table I below for the body surface area (BSA) of the particular patient, and a particular vein through which the catheter is to extend: namely the right internal jugular vein (RIJV); the right subclavian vein (RSCV); the left internal jugular vein (LIJV); or the left subclavian vein (LSCV):
3. As a final step, the venous catheter is implanted in the desired venous system of the patient, with the distal tip of the catheter being in or adjacent to the upper right atrium of the heart.
Alternatively, a similar method for selecting and implanting a permanent venous catheter into the patient may comprise the similar steps of: (1) determining the body surface area (BSA) of the patient; (2) selecting a permanent venous catheter having an actual length from the catheter distal tip to the point on the catheter where it is to penetrate the wall of the desired vein into which it is to be implanted, said actual length of the catheter being within 10% of a desired length as indicated in Table 2 below for the body surface area (BSA) of the particular patient and the particular vein through which the catheter is to extend (RJIV; RSCV; LIJV; or LSCV.)
3. As a third step, one implants the selected venous catheter in the desired venous system of the patient with the distal tip of the catheter being in or adjacent to the upper right atrium of the heart.
As a further optional step, after selecting the desired actual catheter length and the particular vein for implantation, one selects a desired flow rate for the catheter, to obtain a catheter having an actual length within 10% of the desired length and an actual inner diameter within 3% of a desired inner diameter as indicated in Table 3 below, correlated with the actual length.
Desired tubing internal diameter in relation to tubing length at constant flow/pressure relationship.
By way of clarification, the term xe2x80x9cdesired lengthxe2x80x9d is a theoretical, perfect length for the catheter under the selected circumstances. However, in view of practicalities, the actual length of the catheter is of course the length of the actual catheter selected, which is preferably within 10% of the desired length, and preferably within 5% thereof.
If desired, a catheter of known length maybe selected without recourse to body surface area, following which a desired catheter inner diameter maybe selected correlating with the actual length, depending upon the expected flow rate through the catheter, in accordance with this invention.
Thus, a properly sized permanent, venous catheter may be selected and used for a particular patient and a particular site of implantation by a system which correlates with the body surface area (BSA) of the patient to obtain an optimum catheter length, either a length that extends from the catheter distal tip to its integral proximal end or a length of that portion of the catheter which is actually implanted in the particular vein. It should be added that the integral, proximal end of the catheter represents the end of the catheter without any detachable extension tubes or the like, and which integral proximal end of the catheter typically extends out through the skin of the patient after implantation by a short distance, for example, two to six cm. Then, as disclosed in my previous U.S. Pat. No. 5,405,320 and others, an extension tube may be attached to the catheter proximal end, so that the regular and frequent catheter connection and disconnection to hemodialysis sets can be made against the extension tube. Then, when the extension tube wears out, it maybe replaced, so that wear on the actual catheter itself is minimized.
With a properly selected catheter length for the particular patient and the chosen site of venous implantation, one may select a desired flow rate through the catheter, and from that, one may select a desired inner diameter dependent upon the actual length of the catheter, which inner diameter optimally balances the desired flow rate through the catheter with a minimum catheter diameter, to minimize interference with blood flow in the vein by the implanted catheter, while providing adequate, desired blood flow through the catheter. In particular, longer catheters may, with the inner diameters proposed herein, have equal and proper blood flow rates at normal pressures of hemodialysis when compared with shorter catheters.
In accordance with this invention, to select a catheter for one of the permanent venous implantations as illustrated in FIGS. 1 and 2, one may first determine the body surface area of the patient, for example by the well-known method of DuBois et al.; Arch. Int. Med. 17: 863-871 (1916).
From the body surface area and the desired vein in which implantation is to be made (RIJV, RSCV, LIJV, or LSCV), one can determine the desired length in cm. in accordance with Table 1 or Table 2, depending upon which length of the catheter is desired to be used for catheter selection. Then, an optimum tubing inner diameter for the catheter may be determined from the length of the catheter determined in the previous step in accordance with Table 3. Based on this, an actual catheter may be selected which is within 10% of the desired length and 3% of the desired inner diameter. Such a catheter may be implanted, and will exhibit improvements with that particular patient over catheters of differing dimensions. These improvements may comprise a decreased probability of atrial thrombosis, coupled with improved probability of appropriate blood flow, optimization of blood flow, less vein thrombosis and stenosis, increased probability of adequate dialysis, improved catheter survival, and decreased patient morbidity.
If desired, one may correlate a catheter""s length to its desired inner diameter without regard to the body surface area of the patient. This in itself can provide significant advantages of flow optimization.
Straight line interpolation from the various Tables may be used when needed.
Advantages and Disadvantages of Dual Lumen Catheters
The main advantage of dual lumen catheters is convenience of insertion. Instead of two punctures only one puncture is required. This decreases the insertion time considerably and may decrease complication rates related to the insertion procedure itself. This feature was very important when stiff catheters for acute dialysis were used because the catheter was inserted for only a few days. For chronic dialysis this feature is less relevant, because the catheters are used for several months or years and decrease of thrombotic and infectious complications takes precedence over convenience and complication rates during insertion. Besides, complication rates during insertion of soft catheters are very low.
The main disadvantage of dual catheters is their large diameter. The larger diameter the more damage to the vessel wall and the higher exit-site infection rates. As mentioned above, compared to single lumen catheter, dual lumen catheter is stiffer at the same durameter (hardness) of material. Consequently the damage to the pressure points (see above) is more pronounced.
Disadvantages of Single Lumen (Canaud and Tesio) Catheters
The major advantages of single lumen catheters are their smaller diameter and better flexibility. This decreases damage to the vessel wall, vein intima, and decreases exit site infection rates. If both catheters are implanted into the same vein, then the total diameter of two catheters is bigger than that of dual lumen catheter. The advantage of smaller lumen shows only if the catheters are implanted through two veins, e.g., jugulars on each side or jugular and subclavian on the same side. It is worth stressing that the diameter of brachiocephalic veins is bigger than diameter of either jugular or subclavian veins (Table 2).
In this invention, the catheters for long-term hemodialysis access are intended to be inserted into the upper right atrium through one of the following veins:
1. Right internal or external jugular vein
2. Left internal or external jugular vein
3. Right subclavian vein
4. Left subclavian vein
The intravenous catheter of this invention comprises a flexible catheter body, which may be made of medical grade polyurethane, silicone rubber or equivalent material. The catheter may have either single lumen or two lumens. The distal end portion defines flow tubing for blood communication between the lumen and the vein. The tip of the catheter may be provided with side hole(s), although preferably the holes should be absent. The proximal end portion defines a flow tubing for communication with the extension set, which may be coupled with any blood withdrawal and/or intravenous fluid delivery system, such as hemodialyzer, hemofilter, plasmapheresis apparatus, etc. The catheter is preferably provided also with one or two cuffs (subcutaneous or external and deep or internal), which are the bands of fabric affixed to the catheter body (tubing) for fibrous tissue ingrowth in the catheter tunnel.
Implantation of the catheter may be performed either surgically in an operating room or in a procedure room under sterile conditions. After anesthetizing the skin over the intended insertion site, a small, 1-3 cm skin incision is made and dissected bluntly closer toward the vein. The Seldinger method of catheter insertion, already described above, is a preferred method of catheter insertion into the vein. The catheter length and diameter is chosen according to the body size as shown in the table below. A proximal end portion is then used as a gauge to mark the positions of the external cuff and the exit. Using a small hemostat or other suitable instrument a tunnel is made from the incision to the level where the external cuff will lodge. A trocar with the external diameter identical to the catheter tubing is attached to the external end of the catheter, passed through the exit site and the catheter is pulled through the exit. An extension set is then attached to the catheter, and the catheter is covered with immobilizing dressing. Because the external cuff is bigger then the last portion of the subcutaneous tunnel, the catheter cannot dislodge outside, thus no anchoring suture is needed at the exit site.
Relative to the human body after the implantation the catheter consists of three segments: 1) intravenous catheter segment is the part of the catheter located intravenously; the length of this part in relation to body surface area is given in table 2; 2) intramural catheter segment is the part of the catheter contained within the tunnel; and 3) external catheter segment is the part of the catheter outside the skin exit. The catheter tunnel is the passageway through the thoracic wall within which the catheter is contained. Internal tunnel exit is the inlet of the tunnel into the vein. Skin exit is the skin outlet of the tunnel. Subcutaneous or superficial or outer or external cuff is located close (1-3 cm) to the skin exit. The inner or deep cuff is located 2-6 cm from the external cuff, closer to the vein. The part of the tunnel between the skin exit and the outer cuff constitutes the sinus tract.
The catheter may be made radiopaque by addition of barium sulfate or other suitable material into the catheter body. This will facilitate visualization of the catheter on an X-ray.
Subcutaneous cuffs provide both bacteriological barrier against tunnel infection and anchoring means of the intramural and external catheter segments minimizing the movement of the catheter into and out of the tunnel. As mentioned above, such a movement predisposes to contamination of the tubing with introduction of contaminants into the sinus tract after its retraction. Downward directed skin exit for the catheter further decreases chances of sinus tract contamination with the down flowing sweat and bacteria laden water. Also, downward directed exit facilitates pus drainage should infection occur.
The external segment of the catheter typically protrudes about 2 to 6 cm., typically about three cm. out of the skin and may be attached to an extension set consisting of a connector having a flexible extension tube, approximately 8 centimeters in length and equipped with a female luer lock adapter and sealing cap. The extension set is attached to the catheter body after the catheter is inserted into the vein and the subcutaneous tunnel is created. If the extension set is attached to the catheter body before implantation, then the standard tunneling method must be used. During the connection procedure for fluid delivery and/or blood egress the extension tube is clamped, the cap is removed and an appropriate male A male luer adapter is coupled with the female luer lock adapter of the extension tube. After prolonged use, the extension tube may be damaged to the extent that it has to be replaced. The connector facilitates the replacement without the necessity of the catheter removal.
One single lumen catheter may be used for drug delivery, parenteral nutrition, and blood withdrawal for repeated laboratory tests. Although one catheter may be used for blood purification procedure (hemodialysis, plasmapheresis, hemofiltration, etc) two catheters are preferred, one for inflow and one for outflow. If two catheters are inserted, the tips of the catheters should preferentially be a few centimeters apart with the outflow closer to the right atrium. Two catheters may be inserted through the same vein or through two veins. From the convenience point of view it is better to insert both catheters through the same vein; however, to avoid damage of vein wall, vein thrombosis and stenosis the vein should not be filled too tightly, so it is better to insert the catheters through two veins. Any combination of insertion sites may be used, e.g., one catheter inserted through the right internal jugular vein and the other through the left subclavian vein. As mentioned above, dual lumen catheters are more convenient from the insertion point of view. The Tables above provide optimum lumen lengths for dual lumen catheters in the same manner as single lumen catheters.