A power transmitting shaft includes a coupling member, a cylindrical intermediate member, a tube member and an increased diameter portion. The coupling member connects to a counterpart. The cylindrical intermediate member is on a side of one end of the coupling member and has a mechanical strength larger than that of the coupling member. The tube member has one end portion connected to either one of an inner circumferential portion of the intermediate member and an outer circumferential portion of the intermediate member. The increased diameter portion is on one end portion of the intermediate member which is opposed to the one end of the coupling member in an axial direction of the power transmitting shaft. The increased diameter portion is connected with the one end of the coupling member in the axial direction.

The present invention relates to a power transmission shaft, for instance, adapted to transmit a power from a gear shifter to driving wheels of a vehicle, and relates to a vehicular propeller shaft.
Conventionally, there has been proposed an elongated propeller shaft for a vehicle which transmits power from a transmission (or a change-speed gearbox) to a differential gear. The propeller shaft is constituted of two or three parts, and include a tube made of a fiber-reinforced plastic material and Cardan joints coupled to opposite end portions of the tube.
One of the joints includes a yoke that is press-fitted to one of the end portions of the tube, and a sleeve yoke that has one end attached to the side of the transmission and an opposed end connected to the yoke. The other of the joints includes a yoke that is press-fitted to the other of the end portions of the tube, and a flanged yoke that has one end attached to the side of the differential gear and an opposed end connected to the yoke.
The respective yokes include generally fork-shaped yoke bodies and cylindrical intermediate portions that has serrations on an outer circumferential surface thereof. The intermediate portions are connected with end portions of the yoke bodies which are located on a side of the tube. The yoke bodies and the intermediate portions are made of an iron-based metal and integrally formed with each other.
The tube is coupled to the yokes through the serrations by press-fitting the opposite end portions of the tube onto the outer circumferential surfaces of the intermediate portions.
Japanese Patent Application First Publication No. 2003-184853 discloses such a vehicular propeller shaft.

Power transmission shaft and propeller shaft for vehicle


A process for simultaneously coating and forming a body. The process includes moving two mold halves into contact with one another; introducing an injection-molding material into the mold halves so that a molding is formed; evacuating the molding; admitting a gas into the molding; igniting a plasma in the molding so that a coating is deposited on the inner side of the molding; and moving the mold halves apart so that the molding drops out.

1. Field of the Invention
The invention relates to a process and an apparatus for coating and forming a body and to a body produced thereby.
2. Description of Related Art
To reduce the permeation of gases and liquids in the field of plastic packaging and to protect the plastic material from chemical attack or UV radiation, it is advantageous for substrate materials, in particular three-dimensional hollow bodies, to be provided with a coating, in particular a barrier coating. Coatings allow the same property to be achieved with inexpensive bulk plastics as with expensive specialty plastics and make it possible to replace glass, for example, in the field of pharmaceutical packaging materials with bulk plastics of this type. Applications of coatings to a plastic substrate have been disclosed by the following applications:
U.S. Pat. No. 5,798,139
U.S. Pat. No. 5,833,752
U.S. Pat. No. 6,001,429
U.S. Pat. No. 5,798,139 describes the production of plastic containers with a carbon film coating. The carbon film is intended to form a gas barrier and to solve the problem of sorption from the plastic material.
U.S. Pat. No. 5,833,752 has disclosed a system in which the barrier coating is applied from a plasma. The energy used to maintain the plasma is applied by devices which are distinguished by the fact that the energy is introduced into the interior of the containers to be coated via an outer electrode.
is U.S. Pat. No. 6,001,429 again discloses the application of a barrier layer to the inner surface of a plastic substrate, with HMDSO as monomer gas together with an oxygen carrier gas being passed into the interior of the item which is to be coated.
WO 99/17334 has disclosed a process for internal or external coating, in which a coating apparatus for coating a plastic container has been combined with a stretch blow molding device. A drawback of the apparatus which is known from WO 99/17334 is that it is in each case only possible to produce one hollow body per coating station. A further drawback is that the apparatus which is known from WO 99/17334 cannot be used to produce bodies of any desired shape.

Method and device for the simultaneous coating and moulding of a body


There is provided a water-based liquid tooth cleaning gel with a viscosity below 50 Paxc2x7s (20xc2x0 C.), comprising

This invention relates to liquid tooth cleaning preparations containing polishes, humectants, tartar-inhibiting antimicrobial agents and water which are substantially transparent or clear and which show favorable rheological behavior for dispensing from small flexible plastic bottles.
Liquid tooth cleaning preparations which can be dispensed under light pressure from small flexible plastic bottles are already known, for example from WO 94/01080 A1. These products are white or opaque in appearance. DE 2033678 B2 describes toothpastes which contain a silica polish and a humectant combination containing polyethylene glycols with molecular weights in the range from 800 to 2,000. These products are clear or transparent in appearance. EP 0 754 027 B2 describes liquid tooth cleaning preparations containing a silica polish and a humectant combination of sorbitol and a low molecular weight polyethylene glycol.
The problem addressed by the present invention was to provide water-based liquid tooth cleaning gels having high transparency and a content of antimicrobial agents for controlling tartar. It has been found that both the liquid consistency and high transparency can be achieved if the products contain less than 50% by weight of sorbitol and 0.1 to 5% by weight of a polyethylene glycol with an average molecular weight of 800 to 10,000 and 0.1 to 1% by weight of an antimicrobial agent selected from triclosan, hexetidine and mixtures thereof.
Accordingly, the present invention relates to a water-based liquid tooth cleaning gel with a viscosity below 50 Paxc2x7s (20xc2x0 C.), characterized by a content of
Liquid in the context of the present invention means a viscosity of less than 50 Paxc2x7s (as measured at 20xc2x0 C. with a Brookfield RVF rotational viscosimeter, spindle xc2xe at 4 r.p.m. corresponding to a shear rate D of 4 Sxe2x88x921) which provides for dispensing from a small flexible bottle by light pressure and ensures that the gel sinks slowly into the bristles of the toothbrush.
The transparency of the tooth cleaning gel should be at least so high that text with a letter height of ca. 4 mm and a letter width of 3 mm is still easy to read through a ca. 1 cm thick layer of the tooth gel (for example in a clear glass cell with an edge length of 1xc3x971xc3x974 cm). The viscosity and transparency according to the invention are achieved through the choice and quantity of the polishing components, thickeners and humectants used.
Suitable silica polishing components are any silica gels, silica hydrogels and precipitated silicas known as polishes. Silica gels are obtained by reacting sodium silicate solutions with strong aqueous mineral acids to form a hydrosol, ageing to form the hydrogel, washing and drying. If drying is carried out under moderate conditions to a water content of 15 to 35% by weight, the so-called silica hydrogels known, for example, from U.S. Pat. No. 4,153,680 are obtained.
Drying to water contents below 15% by weight results in irreversible shrinkage of the previously loose structure of the hydrogel to the dense structure of the so-called xerogel. Silica xerogels are described, for example, in U.S. Pat. No. 3,538,230.
A second particularly suitable group of silica polishing agents are the precipitated silicas. Precipitated silicas are obtained by precipitation of silica from dilute alkali metal silicate solutions by addition of strong acids under conditions which preclude aggregation to the sol and gel. Suitable processes for the production of precipitated silicas are described, for example, in DE-OS 25 22 486 and in DE-OS 31 14 493. A particularly suitable precipitated silica is that produced in accordance with DE-OS 31 14 493 which has a BET surface of 15 to 110 m2/g, a particle size of 0.5 to 20 xcexcm (at least 80% by weight of the primary particles should be below 5 xcexcm in size) and a viscosity in the form of a 30% glycerol/water (1:1) dispersion of 30 to 60 Paxc2x7s (20xc2x0 C.) and which is used in a quantity of 10 to 20% by weight, based on the tooth gel. In addition, particularly suitable precipitated silicas of this type have rounded corners and edges and are commercially obtainable under the name of Sident(copyright)12 DS (DEGUSSA). Another suitable silica is Zeodent 113 (Huber Corp.) with a BET surface of 150 to 250 m2/g.
Other precipitated silicas of this type are Sident 8 (DEGUSSA) and Sorbosil AC 39 (Crosfield Chemicals). These silicas are distinguished by a weaker thickening effect and a slightly larger mean particle size of 8 to 14 xcexcm for a specific BET surface of 40 to 75 m2/g and are particularly suitable for liquid tooth gels according to the present invention.
Other polishes, particularly those with a refractive index differing from 1.45 xcexcm by more than 0.1, are preferably not present at all or are present at most in quantities of less than 2% by weight. Such polishes are, for example, pumice, zirconium silicate or gamma-aluminium oxide.
Of crucial importance to the rheology and transparency of the liquid tooth cleaning gels according to the invention is the composition of the liquid carrier phase of water and humectants. The total quantity of 40 to 60% by weight of the humectant combination is based on the tooth cleaning gel as a whole and consists essentially of sorbitol and polyethylene glycol. However, the quantity of sorbitol should be below 50% by weight. Glycerol may optionally be present in quantities of less than 10% by weight. Suitable polyethylene glycols are the relatively high molecular weight types with average molecular weights of 800 to 10,000 and preferably in the range from 1,000 to 40,000. The water content of the tooth gels according to the invention is in the range from 25 to 35% by weight and is the sum of the quantities of water introduced by the raw materials, such as 70% sorbitol or 86% glycerol for example, and the quantities separately added. The quantities of sorbitol and glycerol mentioned are based on water-free active substances.
Particularly suitable antimicrobial agents for inhibiting the formation of plaque are 2,2,4xe2x80x2-trichloro-2xe2x80x2-hydroxydiphenylether (triclosan) and 1,3-bis-(2-ethylhexyl)-5-mthyl-5-aminohexahydropyrimidine (hexetidine) and mixtures of these antimicrobial components. The hexetidine may also be present in the form of a water-soluble salt, for example the benzoate, terephthalate or salicylate. These selected antimicrobial agents can be incorporated particularly clearly and stably in the tooth gels according to the invention.
In addition to the compulsory components mentioned, the tooth cleaning gels according to the invention may contain 1 to 10% by weight of other toothpaste ingredients which, in type and quantity, do not adversely affect transparency. Such ingredients are, for example, binders, surfactants, flavors and sweeteners, scale inhibitors, fluorine compounds, vitamins, panthenol and other active substances.
Suitable binders are, for example, natural and/or synthetic water-soluble polymers, such as alginates, carrageenates, tragacanth, starch and starch ethers, cellulose ethers such as, for example, carboxymethyl cellulose (Na salt), hydroxyethyl cellulose, methyl hydroxypropyl cellulose, guar, acacia gum, agar agar, xanthan gum, succinoglycan gum, locust bean gum, pectins, water-soluble carboxyvinyl polymers (for example Carbopol(copyright) types), polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycols, more particularly those with molecular weights of 1,500 to 1,000,000.
Particularly suitable binders are xanthan gum, carboxymethyl cellulose, polyvinyl pyrrolidone and mixtures of these water-soluble polymers which may be present in a quantity of up to 1.0% by weight.
Suitable surfactants are, for example, sodium alkyl sulfates containing 12 to 18 carbon atoms in the alkyl group. These compounds also have an enzyme-inhibiting effect on the bacterial metabolism of tartar. Other suitable surfactants are alkali metal salts, preferably sodium salts of alkyl polyglycol ether sulfate containing 12 to 16 carbon atoms in the linear alkyl group and 2 to 6 glycol ether groups in the molecule, of linear alkane (C12-18) sulfonate, of sulfosuccinic acid monoalkyl (C12-18) esters, of sulfated fatty acid monoglycerides, sulfated fatty acid alkanolamides, sulfoacetic acid alkyl (C12-16) esters, acyl sarcosines, acyl taurides and acyl isethionates containing 8 to 18 carbon atoms in the acyl group.
Ampholytic and zwitterionic surfactants, more particularly betaine surfactants, for example cocoalkyl betaine or cocoacylamidopropyl betaine, are also suitable. Finally, nonionic surfactants, for example ethoxylates of fatty acid mono- and diglycerides, of fatty acid sorbitan esters and alkyl (oligo)glucosides, may also be used.
In a preferred embodiment, the tooth cleaning gels according to the invention contain a water-soluble binder and a surfactant combination of anionic, zwitterionic and nonionic surfactants as further ingredients. The surfactants are preferably present in a quantity of 0.5 to 3% by weight, the quantity ratio of anionic to zwitterionic and nonionic surfactants preferably being 1:(0.2-1).
Flavors and sweeteners are normally used for flavoring. Suitable flavors are, for example, peppermint oil, spearmint oil, eucalyptus oil, aniseed oil, fennel oil, caraway oil, methyl acetate, cinnamaldehyde, anethol, vanillin, thymol and other natural or nature-identical essential oils or even synthetic flavors.
Suitable sweeteners are, for example, saccharin sodium, acesulfam, aspartame, sodium cyclamate, steviosides, thaumatine, sucrose, lactose, maltose or fructose, glycyrrhizin, etc.
Suitable scale inhibitors are, for example, organic phosphonates, such as azacycloheptane-2,2-diphosphonic acid disodium salt or 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt. Suitable fluorine compounds are, for example, sodium fluoride and sodium monofluorophosphate (Na2PO3F).
The vitamins present may be selected, for example, from retinol, panthenol or a salt of pantothenic acid, ascorbic acid or mixtures thereof. In a preferred embodiment, a combination of panthenol and retinol is present for improving the inflammation-inhibiting properties.
In addition, a content of certain dissolved divalent metal salts, more particularly salts of magnesium and zinc, has proved to be valuable for the remineralizing properties of the tooth cleaning gels according to the invention. Suitable metal salts are, for example, the sulfates, fluorides, citrates or acetates of these metals. A preferred embodiment is characterized by the presence of dissolved salts of magnesium or zinc or a mixture of both salts in a quantity of 0.02 to 0.2% by weight Mg++ and/or Zn++.
The tooth cleaning gels according to the invention may additionally contain, for example,
buffering agents, for example primary, secondary or tertiary alkali metal phosphates, citric acid/Na citrate,
wound-healing and anti-inflammatory agents such as, for example, urea, allantoin, camomile-based active principles, such as azulene, alkali metal thiocyanate, acetylsalicylic acid derivatives,
lower alcohols, for example ethanol, isopropanol, and
dyes and pigments.
The following Examples are intended to illustrate the invention.

Plaque-controlling liquid tooth cleaning agent


A network device is presented comprising a filtering database, a link state database and a controller, coupled to each of the filtering database and the link state database, to process data received from remote network devices based, at least in part, on distance vector information stored in the filtering database, link state information stored in the link state database, and content of the received data.

A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise expressly reserves all rights whatsoever in said copyright works.
1. Field
The present invention relates to the field of networking and,in particular, to a method and apparatus for dynamically managing the topology of a data network.
2. Background Information
As computer technology has evolved, so too has the use of data networks to communicatively couple computer systems together, enabling them to communicate with one another. Data networks come in many different sizes and network topologies. From small peer-to-peer networks enabling multiple users of a small office to share data, to more formal local area networks (LAN), wide-area and global data networks (e.g., the Internet). Those skilled in the art will appreciate that the management of such data networks has become a mission critical function for many enterprises.
One commonly used measure of network performance and manageability is the time required by network core devices to identify optimal routing paths (or, re-routing in the event of failure) between network elements, a measure colloquially referred to as a network""s xe2x80x9cconvergence timexe2x80x9d. Those skilled in the art will appreciate that convergence is not an easy task, as there often exists a number of alternate paths to each network element, often resulting in undesirable physical loops. Accordingly, many network devices utilize routing protocols with convergence algorithms that are designed to identify and eliminate unwanted physical loops. The complexity of the routing protocol and, consequently, the convergence algorithm is often dictated by the processing power of the network devices populating the network and the network layer of interest.
The processing power of network devices varies between devices and, quite often, on which xe2x80x9clayerxe2x80x9d of the network the device is to operate. Those skilled in the art will appreciate that use of the term xe2x80x9cnetwork layerxe2x80x9d refers to the layers defined in the Open System Interconnection (OSI) network model. Routers operating at the network layer (layer 3), for example, are typically configured with more processing power and memory than bridges (or switches, which are really just multiport bridges) operating at the link or Media Access Control (MAC) layer (layer 2). Accordingly, the protocols employed by network devices vary depending upon which network layer is being discussed.
In general, there are two types of convergence protocols: link state protocols and distance vector protocols. Link state protocols are typically used by routers in layer 3 of the network to identify optimal network routing paths by flooding routing information to all of the network devices resident within that layer of the data network. In accordance with the link state protocol, each network device sends only that portion of the routing table that describes the state of its own links. One popular example of a link state protocol is the Open Shortest Path First (OSPF) protocol developed and standardized by the Internet Engineering Task Force (IETF).
In contrast, distance vector algorithms are typically utilized by bridges to identify the optimal network routing paths at the link layer (e.g., layer 2) of the OSI network model. A popular prior art distance vector algorithm utilized in layer 2 convergence protocols is the Spanning Tree Protocol (STP), developed by Radia Perlman and standardized in IEEE 801.2d. STP is a protocol designed to allow bridges to map a network topology (e.g., the active topology) while eliminating loops which could lead to broadcast storms essentially crippling network performance. Those skilled in the art will appreciate, however, that as network traffic has increased, the popularity of the STP as a network management protocol has diminished due to the inherent latency required to establish new routing paths once a fault has been detected. In some instances, it may take several minutes to reconnect a network device that has been isolated due to a fault in the network. Due to the relatively lengthy convergence times associated with STP, networking administrators have been pressuring device manufacturers for an improved layer 2 networking device that reduces or eliminates the reliance on distance vector algorithms to control the network topology of a data network.
Several solutions have been proposed and implemented in switching products by various vendors, most of which come in the form of a proprietary enhancement to the STP standard protocol. One example of just such a solution is the UplinkFast(trademark) technology from Cisco Systems Inc. of San Jose, Calif. The Spanning Tree UplinkFast(trademark) protocol is designed to improve convergence time, while still adhering to the basic STP standard. Simplistically, the UplinkFast(trademark) solution creates virtual groups of ports into uplink groups wherein the STP configures ports an uplink group at a time. One of the limitations of the UplinkFast(trademark) solution, however, is that it physically turns links off when potential loops are identified. Those skilled in the art will appreciate that turning off a link, as done in the UplinkFast(trademark) solution, eliminates the possibility for redundancy, thereby increasing the convergence time should a link fail. In addition, although the UplinkFast(trademark) approach has, indeed, reduced the time required for basic STP convergence, it is an incremental improvement at best.
Another drawback of the STP is its inability to accommodate load balancing, and other more advanced network services such as Quality of Service (QoS). That is, insofar as the STP establishes an active topology void of redundant paths and loops, it forecloses any opportunity for load sharing among multiple links leading to the same point insofar as those multiple links may well represent a broadcast loop. To date, this limitation of the distance vector protocols have not been addressed by device manufacturers.
Thus, it would be desirable to provide an innovative solution that improves convergence time while providing for load sharing and other advanced network services, without negatively affecting network reliability attributes. More specifically, a method and apparatus for dynamically managing the topology of a data network that is unencumbered by the inherent deficiencies and limitations commonly associated with the spanning tree protocol and other prior art solutions.
In accordance with the teachings of the present invention, a method and apparatus for dynamically managing the topology of a data network is provided. In particular, in accordance with one embodiment of the present invention, the apparatus comprises a filtering database, a link-state database, and a controller. Coupled to each of the filtering database and the link-state database, the controller processes data received from remote network devices based, at least in part, on distance vector information stored in the filtering database, link state information stored in the link state database, and content of the received data.
Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments of the invention in conjunction with accompanying figures.

Dynamically managing the topology of a data network


The present invention relates to methods of cleansing and moisturizing skin using multiphase extruded soap bar achieving hardness of a discontinuous phase is at least two times the hardness of a continuous phase in which it is found.

The invention relates to multiphase personal washing bars having an artisan-crafted appearance that can be made by a high throughput extrusion process and is suitable for everyday use. The bars comprise a discontinuous phase having its longest dimension between about 3 and about 75 mm that is dispersed in a continuous phase containing a cleansing base. By ensuring the hardness of the continuous phase is within certain limits, and that the ratio of the hardness of the two phases measured at specific temperatures is greater than a critical value, it is possible to extrude the composition at high speed (e.g., at least about 200 bars/minute, preferably in excess of 300 bars/minute) while maintaining spatially distinct regions at the surface of the bar as measured by a visual discrimination panel test. Plasticizing and hardening agents that can be used to alter the rheology of the phases in order to meet these constraints are described.
The invention further relates to methods of cleansing, moisturizing, and/or refreshing the skin using bars as noted comprising various skin nutrients, skin conditioners and/or skin benefit agents.
Multicolor or multiphase soaps have been described by various terms that include variegated, marbled, striated, and striped. Prior art has mainly focused on routes to reproducibly achieve spatial variation in dye or pigment concentration as the primary means of generating bars that appear as comprising multiple phases.
Key technical problems that were recognized early in the commercial exploitation of such bars were: efficient manufacture with consistent patterns; distinctive contrast between the different colors especially at the bar surface; and the elimination of cracking, fissuring, and color migration (xe2x80x9cbleedingxe2x80x9d) during storage and use. Commercial processes and machines are now available to produce multicolor soaps that have highly consistent appearance.
The multicolor nature of the prior art bars gives the impression that the bars comprise distinct phases that have different ingredients or function. However, the vast majority of multicolored bars disclosed in the art and sold in the mass market have virtually homogeneous composition and few different properties apart from gradients in coloring agents. Incomplete mixing during manufacture of the bar essentially produces these dye gradients.
With the resurgence in the specialty soap market, consumers are being offered multicolor/multiphase bars that have a much more hand crafted (i.e., xe2x80x9cartisan craftedxe2x80x9d) xe2x80x9cone-of a kindxe2x80x9d appearance. Technically such bars have at least the following three characteristics that contribute to their distinctive appearance: i) The sharpness of the boundary between the phases; ii) an easily recognizable difference in optical texture and/or pattern that goes beyond color, and iii) a certain degree of bar to bar non-uniformity. Differences in optical texture and pattern are especially important to convey a collection of sensory expectations associated with that phase. Examples include translucency, shine, and sharp edges to convey a gel; circular dark patterns or repeating textures to convey fruit, etc.
Artisan soaps are predominantly made by cast melt processesxe2x80x94either single casting or sequential multiple casts. Because these cast melt processes are slow and labor intensive, multiphase artisan soaps are relatively expensive and confined to upscale specialty shops and outlets. Furthermore, cast melt soaps are known to have high wear rates and mushing characteristics that make them less preferred for everyday use.
One objective of the present invention is a multiphase bar soap that has an artisan-crafted appearance yet can be produced by a conventional high speed (e.g., at least about 200 bars/minute) extrusion process with only minor equipment modifications and requires minimum (preferably no), trimming.
A second objective is an extruded multiphase soap wherein the phases have sharp boundaries, recognizable differences in optical texture and pattern, and different composition.
A third objective is a multiphase soap having an artisan-crafted appearance that has in-use properties and unit-cost that will make it suitable for the mass market.
A still further objective is the production of extruded multiphase soap bars that will have adequate bar to bar variability to convey distinctiveness.
Another objective of this invention is to provide methods for cleansing, moisturizing and/or refreshing the skin using bars of the invention comprising skin nutrients, skin conditioners and/or skin benefit agents.
As will be shown, these and other objectives can be met by following the teachings of the present invention.
U.S. Pat. No. 3,673,294 to Matthaei et al, teach a process to form multicolored bars by extruding a mixture of two noodles which are required to have the same viscosity and essentially the same hardness (penetration value).
U.S. Pat. No. 3,940,220 to D""Arcangeli teaches the extrusion of a mixture of two noodles in which it is required that the discontinuous phase be softer (lower penetration value) than the main soap. In the subject invention, the discontinuous phase is harder.
U.S. Pat. No. 3,993,722, to Borcher et al and U.S. Pat. No. 4,092,388 to Lewis teach processes of combining different colored noodles to formed marbled soap. The two noodles have essentially the same composition (e.g., hardness) apart from colorant and the two different color noodles have essentially the same temperature at the time of extrusion.
U.S. Pat. No. 4,310,479 to Ooms et al teaches a process for combining a minor amount of opaque noodles with transparent noodles to form a transparent marbled bar. The noodles should differ in water content by no more than 3% and are at the same temperature during extrusion. Accordingly, hardness of the noodles and bar is about the same.
U.S. Pat. No. 6,390,797 to Meyers teaches a process for making marbleized or speckled soap by addition of a second stream of colored soap pellets into the interior of the final stage plodder at a specific point. No mention is made about the hardness of the two phases or their required properties or of processes of making, or methods of using, bars of the invention.
U.S. Pat. No. 3,884,605 to Grelon teaches an apparatus for making striated soap made by coextrusion where it is desirable that the two soaps have identical material properties, e.g., hardness, apart from color.
U.S. Pat. No. 6,383,999 to Coyle et al teach a coextruded multiphase bar in which the phases differ in the level of emollient but must have similar flow properties under extrusion process conditions.
U.S. Pat. No. 5,935,917 to Farrell et al, U.S. Pat. No. 5,972,859 to Farrell et al and U.S. Pat. No. 5,981,464 to He et al teach bar compositions comprised of surfactant chips mixed with a second chip comprised predominantly of polyether and containing an emulsified benefit agent. The polyether chips are friable by design so that they disperse when mixed with the soap chips.
None of these patents teach that the discontinuous phase of a multiphase bar should be at least twice as hard as the soap mass that will become the continuous phase of the bar when these two phases first come into contact prior to the final extrusion. For example many patents teach the combining of different color noodles in the vacuum chamber of a two stage refiner-plodder. However none of these patents teach that one noodle should be at least twice as hard as the other colored noodle when these noodles are initially combined.
Further the art does not teach appropriate plasticizers and hardening agents that enable these rheological requirements to be met. In fact the large majority of the prior art emphasize engineering approaches (apparatus and different processes) to overcome problems in making acceptable multicolor soaps using soaps of uniform composition apart from coloring agents.
The subject invention describes multiphase personal washing bars that have a artisan-crafted appearance that can be made in a high speed extrusion process by ensuring that the hardness of the discontinuous phase is sufficiently greater than the continuous phase so that it does not excessively deform during extrusion.
More specifically, the invention comprises:
a) a continuous solid phase covering about 65% to 99% by wt final bar composition and comprising 25-90% of the continuous phase composition of a surfactant base suitable for cleansing the skin,
b) a discontinuous phase (present as one or more xe2x80x9cdomainsxe2x80x9d of discontinuous phase within the continuous phase) comprising about 1 to about 35% of final bar composition and that comprises a water soluble or water dispersible solid matrix comprising at least 1 wt % surfactant wherein said discontinuous phase has its longest dimension between about 3 and about 75 mm,
wherein the hardness of the continuous phase is in the range of 1.9 to 2.5 bar. (1 bar equals 100,000 Pascals) when measured at a temperature between 33 and 50xc2x0 C., preferably 33 and 42xc2x0 C.; wherein the ratio, xcex, defined as the hardness of the discontinuous phase measured at a temperature of 25xc2x0 C. divided by the hardness of the continuous phase measured at a temperature of 33xc2x0 C. is greater than 2.0; and wherein said hardness values are measured by the Cylinder Impaction Test;
wherein the discontinuous phase comprises 1 to about 25 wt % of the bar, and
wherein the bar has a descriptive visual grading score of at least 3.0 when measured by Visual Discrimination Panel Test.
The temperature noted above approximately reflects the thermal conditions of each phase during the time of extrusion and, without wishing to be bound by theory, when these conditions are met, the discontinuous phase is believed to not deform excessively, under shear, and therefore, is believed to allow formation of the artisan-type bars.
A second embodiment of the invention, comprises a process for making a bars having an artisan crafted appearance by extrusion wherein said process comprises:
1. adding to noodles comprising the continuous phase of a toilet bar mass that is at a temperature about 33 to 50xc2x0 C., a second solid mass that is in the form of discrete particles having at least one dimension greater than 3 mm to form a mixture, wherein at the time of addition, the hardness of the said second solid mass is at least twice the hardness of the noodles forming the continuous phase toilet bar mass, said hardness values measured by the Cylinder Impaction Test;
2. extruding the mixture so formed in step 1) to form an extruded composite mass comprising a continuous toilet bar mass and a discontinuous phase of the second solid mass;
3. cutting forming the extruded mass into a bar
wherein the discontinuous phase comprises 1 to about 25 wt % of the bar, and
wherein the bar has a descriptive visual grading score of at least 3.0 when measured by Visual Discrimination Panel Test.
In a third embodiment, the invention comprises methods of cleansing and moisturizing the skin wherein said method comprises
a) washing the skin with a multiphase, extruded soap bar wherein the bar has continuous and discontinuous phases as noted and additionally comprises skin benefit agents selected from the group consisting of skin nutrients (e.g., vitamins, liposomes) and skin conditioners (e.g., silk proteins). The methods may also comprise using bars comprising deep cleansing skin benefit agents such as anti-acne agents, oil control agents, and/or antimicrobials, for example; and
b) rinsing the skin with water
The bars of this invention comprise a continuous phase and a discontinuous phase. A critical aspect of the invention is that the hardness of these phases meet specific requirements. In a second embodiment, the invention comprises preparing a continuous phase and discontinuous phase solid mass (defined by difference in hardness, adding together in a mixer at defined temperature range, extruding, and cutting to form final bars. The bars and component phases are discussed in greater detail below
Continuous Solid Soap Phase
The continuous phase comprises 65 wt % to about 99 wt % of the bar composition, preferably 75 wt % to 95 wt % and most preferably 80 to 90 wt %. A key requirement is that the hardness as measured by the Cylinder Impaction Test described below has a value falling in the range of 1.9 to 2.5 bars when measured at a temperature between 33 and 42xc2x0 C. It has been found from experience that when the hardness of the continuous phase falls within this range, it is possible to form bars by extrusion at a high rate. By high rate is meant in excess of 200 bars per minute and preferably greater than 300 bars per minute.
The continuous phase comprises a surfactant or detergent base suitable for cleaning the skin and optionally a plasticizing agent used to control its consistency.
It has also been found preferable for the continuous phase to have a certain degree of plasticity so that it adheres well to the discontinuous phase. The plastic zone size, r, as measured by Three-Point Bend Test described in the Test Methodology section provides a relevant measure of plasticity or brittleness. The continuous phase should have a plastic zone radius greater than 2.0 mm and preferably greater than 2.5 mm. A lower value of the plastic zone size represents a continuous phase sample that is more brittle, a greater value represents a more plastic sample.
It has been found that when the plastic zone radius of the continuous phase is greater than 2.0 mm, a cohesive bar junction between the continuous and discontinuous phase is favored, i.e., the bars don""t crack
Surfactant Base
The primary component of the continuous phase is a surfactant base suitable for cleansing the skin. Generally the surfactant base comprises 25-90 wt % of the continuous phase, preferably between 50 and 80 wt %.
One useful surfactant base comprises fatty acid soaps. The term xe2x80x9csoapxe2x80x9d is used herein in its popular sense, i.e., the alkali metal or alkanol ammonium salts of aliphatic, alkane-, or alkene monocarboxylic acids. Sodium, potassium, magnesium, mono-, di- and tri-ethanol ammonium cations, or combinations thereof, are suitable for purposes of this invention. In general, sodium soaps are used in the compositions of this invention, but from about 1 % to about 25% of the soap may be potassium or magnesium soaps. The soaps useful herein are the well known alkali metal salts of natural of synthetic aliphatic (alkanoic or alkenoic) acids having about 8 to 22 carbon atoms, preferably about 8 to about 18 carbon atoms. They may be described as alkali metal carboxylates of acrylic hydrocarbons having about 8 to about 22 carbon atoms.
Soaps having the fatty acid distribution of coconut oil may provide the lower end of the broad molecular weight range. Those soaps having the fatty acid distribution of peanut or rapeseed oil, or their hydrogenated derivatives, may provide the upper end of the broad molecular weight range.
It is preferred to use soaps having the fatty acid distribution of coconut oil or tallow, or mixtures thereof, since these are among the more readily available fats. The proportion of fatty acids having at least 12 carbon atoms in coconut oil soap is about 85%. This proportion will be greater when mixtures of coconut oil and fats such as tallow, palm oil, or non-tropical nut oils or fats are used, wherein the principle chain lengths are C16 and higher. Preferred soap for use in the compositions of this invention has at least about 85% fatty acids having about 12 to 18 carbon atoms.
Coconut oil employed for the soap may be substituted in whole or in part by other xe2x80x9chigh-lauricxe2x80x9d oils, that is, oils or fats wherein at least 50% of the total fatty acids are composed of lauric or myristic acids and mixtures thereof. These oils are generally exemplified by the tropical nut oils of the coconut oil class. For instance, they include: palm kernel oil, babassu oil, ouricuri oil, tucum oil, cohune nut oil, murumuru oil, jaboty kernel oil, khakan kernel oil, dika nut oil, and ucuhuba butter.
A preferred soap is a mixture of about 30% to about 40% coconut oil and about 60% to about 70% tallow. Mixtures may also contain higher amounts of tallow, for example, 15% to 20% coconut and 80 to 85% tallow.
The soaps may contain unsaturation in accordance with commercially acceptable standards. Excessive unsaturation is normally avoided.
Soaps may be made by the classic kettle boiling process or modern continuous soap manufacturing processes wherein natural fats and oils such as tallow or coconut oil or their equivalents are saponified with an alkali metal hydroxide using procedures well known to those skilled in the art. Alternatively, the soaps may be made by neutralizing fatty acids, such as lauric (C12), myristic (C14), palmitic (C16), or stearic (C18) acids with an alkali metal hydroxide or carbonate.
A second type of surfactant base useful in the practice of this invention comprises non-soap synthetic type detergentsxe2x80x94so called syndet bases.
Anionic Surfactants
The anionic surfactant may be, for example, an aliphatic sulfonate, such as a primary alkane (e.g., C8-C22) sulfonate, primary alkane (e.g., C8-C22) disulfonate, C8-C22 alkene sulfonate, C8-C22 hydroxyalkane sulfonate or alkyl glyceryl ether sulfonate (AGS); or an aromatic sulfonate such as alkyl benzene sulfonate.
The anionic may also be an alkyl sulfate (e.g., C12-C18 alkyl sulfate) or alkyl ether sulfate (including alkyl glyceryl ether sulfates). Among the alkyl ether sulfates are those having the formula:
RO(CH2CH2O)nSO3M
wherein R is an alkyl or alkenyl having 8 to 18 carbons, preferably 12 to 18 carbons, n has an average value of greater than 1.0, preferably between 2 and 3; and M is a solubilizing cation such as sodium, potassium, ammonium or substituted ammonium. Ammonium and sodium lauryl ether sulfates are preferred.
The anionic may also be alkyl sulfosuccinates (including mono- and dialkyl, e.g., C6-C22 sulfosuccinates); alkyl and acyl taurates, alkyl and acyl sarcosinates, sulfoacetates, C8-C22 alkyl phosphates and phosphates, alkyl phosphate esters and alkoxyl alkyl phosphate esters, acyl lactates, C8-C22 monoalkyl succinates and maleates, sulphoacetates, and acyl isethionates.
Sulfosuccinates may be monoalkyl sulfosuccinates having the formula:
R4O2CCH2CH(SO3M)CO2M;
amido-MEA sulfosuccinates of the formula
R4CONHCH2CH2O2CCH2CH(SO3M)CO2M
wherein R4 ranges from C8-C22 alkyl and M is a solubilizing cation; and amido-MIPA sulfosuccinates of formula
RCONH(CH2)CH(CH3)(SO3M)CO2M
where M is as defined above.
Also included are the alkoxylated sulfosuccinates;
wherein n=1 to 20; and M is as defined above.
Sarcosinates are generally indicated by the formula RCON(CH3)CH2CO2M, wherein R ranges from C8 to C20 alkyl and M is a solubilizing cation.
Taurates are generally identified by formula
R2CONR3CH2CH2SO3M wherein R2 ranges from C8-C20 alkyl, R3 ranges from C1-C4 alkyl and M is a solubilizing cation.
Another class of anionics are carboxylates such as follows:
Rxe2x80x94(CH2CH2O)nCO2M
wherein R is C8 to C20 alkyl; n is 0 to 20; and M is as defined above.
Another carboxylate which can be used is amido alkyl polypeptide carboxylates such as, for example, Monteine LCQ(copyright) by Seppic.
Another surfactant which may be used are the C8-C18 acyl isethionates. These esters are prepared by reaction between alkali metal isethionate with mixed aliphatic fatty acids having from 6 to 18 carbon atoms and an iodine value of less than 20. At least 75% of the mixed fatty acids have from 12 to 18 carbon atoms and up to 25% have from 6 to 10 carbon atoms.
Acyl isethionates, when present, will generally range from about 0.5-15% by weight of the total composition. Preferably, this component is present from about 1 to about 10%.
The acyl isethionate may be an alkoxylated isethionate such as is described in Ilardi et al., U.S. Pat. No. 5,393,466, hereby incorporated by reference into the subject application.
Another surfactant which may be used are C8 to C22 neutralized fatty acids (soap). Preferably, the soap used are straight chain, saturated C12 to C18 neutralized fatty acids.
In general the anionic component will comprise from about 1 to 20% by weight of the composition, preferably 2 to 15%, most preferably 5 to 12% by weight of the composition.
Zwitterionic and Amphoteric Surfactants
Zwitterionic surfactants are exemplified by those which can be broadly described as derivatives of aliphatic quaternary ammonium, phosphonium, and sulfonium compounds, in which the aliphatic radicals can be straight or branched chain, and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate. A general formula for these compounds is:
wherein R2 contains an alkyl, alkenyl, or hydroxy alkyl radical of from about 8 to about 18 carbon atoms, from 0 to about 10 ethylene oxide moieties and from 0 to about 1 glyceryl moiety; Y is selected from the group consisting of nitrogen, phosphorus, and sulfur atoms; R3 is an alkyl or monohydroxyalkyl group containing about 1 to about 3 carbon atoms; X is 1 when Y is a sulfur atom, and 2 when Y is a nitrogen or phosphorus atom; R4 is an alkylene or hydroxyalkylene of from about 1 to about 4 carbon atoms and Z is a radical selected from the group consisting of carboxylate, sulfonate, sulfate, phosphonate, and phosphate groups.
Examples of such surfactants include:
4-[N,N-di(2-hydroxyethyl)-N-octadecylammonio]-butane-1-carboxylate;
5-[S-3-hydroxypropyl-S-hexadecylsulfonio]-3-hydroxypentane-1-sulfate;
3-[P,P-diethyl-P-3,6,9-trioxatetradexocylphosphonio]-2-hydroxypropane-1-phosphate;
3-[N,N-dipropyl-N-3-dodecoxy-2-hydroxypropylammonio]-propane-1-phosphonate;
3-(N,N-dimethyl-N-hexadecylammonio)propane-1-sulfonate;
3-(N,N-dimethyl-N-hexadecylammonio)-2-hydroxypropane-1-sulfonate;
4-[N,N-di(2-hydroxyethyl)-N-(2-hydroxydodecyl )ammonio]-butane-1-carboxylate;
3-[S-ethyl-S-(3-dodecoxy-2-hydroxypropyl)sulfonio]-propane-1-phosphate;
3-[P,P-dimethyl-P-dodecylphosphonio]-propane-1-phosphonate; and
5-[N,N-di(3-hydroxypropyl)-N-hexadecylammonio]-2-hydroxy-pentane-1-sulfate.
Amphoteric detergents which may be used in this invention include at least one acid group. This may be a carboxylic or a sulphonic acid group. They include quaternary nitrogen and therefore are quaternary amido acids. They should generally include an alkyl or alkenyl group of 7 to 18 carbon atoms. They will usually comply with an overall structural formula:
where R1 is alkyl or alkenyl of 7 to 18 carbon atoms;
R2 and R3 are each independently alkyl, hydroxyalkyl or carboxyalkyl of 1 to 3 carbon atoms;
n is 2 to 4;
m is 0 to 1;
X is alkylene of 1 to 3 carbon atoms optionally substituted with hydroxyl, and
Y is xe2x80x94CO2xe2x80x94 or xe2x80x94SO3xe2x80x94
Suitable amphoteric detergents within the above general formula include simple betaines of formula:
and amido betaines of formula:
where m is 2 or 3.
In both formulae R1, R2 and R3 are as defined previously. R1 may in particular be a mixture of C12 and C14 alkyl groups derived from coconut so that at least half, preferably at least three quarters of the groups R1 have 10 to 14 carbon atoms. R2 and R3 are preferably methyl.
A further possibility is that the amphoteric detergent is a sulphobetaine of formula
where m is 2 or 3, or variants of these in which xe2x80x94(CH2)3SOxe2x88x923 is replaced by
In these formulae R1, R2 and R3 are as discussed previously.
Amphoacetates and diamphoacetates are also intended to be covered in possible zwitterionic and/or amphoteric compounds which may be used.
The amphoteric/zwitterionic surfactant, when used, generally comprises 0% to 25%, preferably 0.1 to 20% by weight, more preferably 5% to 15% of the composition.
In addition to one or more anionic and optional amphoteric and/or zwitterionic, the surfactant system may optionally comprise a nonionic surfactant.
Nonionic Surfactants
The nonionic which may be used includes in particular the reaction products of compounds having a hydrophobic group and a reactive hydrogen atom, for example aliphatic alcohols, acids, amides or alkyl phenols with alkylene oxides, especially ethylene oxide either alone or with propylene oxide. Specific nonionic detergent compounds are alkyl (C6-C22) phenols-ethylene oxide condensates, the condensation products of aliphatic (C8-C18) primary or secondary linear or branched alcohols with ethylene oxide, and products made by condensation of ethylene oxide with the reaction products of propylene oxide and ethylenediamine. Other so-called nonionic detergent compounds include long chain tertiary amine oxides, long chain tertiary phosphine oxides and dialkyl sulphoxides.
The nonionic may also be a sugar amide, such as a polysaccharide amide. Specifically, the surfactant may be one of the lactobionamides described in U.S. Pat. No. 5,389,279 to Au et al. which is hereby incorporated by reference or it may be one of the sugar amides described in U.S. Pat. No. 5,009,814 to Kelkenberg, hereby incorporated into the subject application by reference.
Other surfactants which may be used are described in U.S. Pat. No. 3,723,325 to Parran Jr. and alkyl polysaccharide nonionic surfactants as disclosed in U.S. Pat. No. 4,565,647 to Llenado, both of which are also incorporated into the subject application by reference.
Preferred alkyl polysaccharides are alkylpolyglycosides of the formula
R2O(CnH2nO)t(glycosyl)x
wherein R2 is selected from the group consisting of alkyl, alkylphenyl, hydroxyalkyl, hydroxyalkylphenyl, and mixtures thereof in which alkyl groups contain from about 10 to about 18, preferably from about 12 to about 14, carbon atoms; n is 0 to 3, preferably 2; t is from 0 to about 10, preferably 0; and x is from 1.3 to about 10, preferably from 1.3 to about 2.7. The glycosyl is preferably derived from glucose. To prepare these compounds, the alcohol or alkylpolyethoxy alcohol is formed first and then reacted with glucose, or a source of glucose, to form the glucoside (attachment at the 1-position). The additional glycosyl units can then be attached between their 1-position and the preceding glycosyl units 2-, 3-, 4- and/or 6-position, preferably predominantly the 2-position.
Examples of cationic detergents are the quaternary ammonium compounds such as alkyldimethylammonium halogenides.
Other surfactants which may be used are described in U.S. Pat. No. 3,723,325 to Parran Jr. and xe2x80x9cSurface Active Agents and Detergentsxe2x80x9d (Vol. I and II) by Schwartz, Perry and Berch, both of which is also incorporated into the subject application by reference.
Although the surfactant may be a pure soap base or a pure syndet base it is in some cases preferable to uses a combination of soaps with synthetic detergents. Examples of combination bases are disclosed in U.S. Pat. No. 4,695,395 to Caswell, et al.
Plasticizing agents (e.g., in continuous phase)
It is may be possible to tailor the surfactant base so that its hardness is in the required range, e.g., by adjusting the titre of the fat charge (softening) in the case of soap or the water content. However, this can often compromise user properties and impact cost. Consequently a second very useful component of the continuous phase is a plasticizing agent. Here we define plasticizing agent as a material that may alter both the hardness and the consistency (e.g., the plastic radius) of the continuous phase, especially at temperatures at which the multiphase bar is extruded and stamped. Without being bound by theory, these materials are thought to facilitate the flow of the continuous semi-solid mass around the dispersed phase during final extrusion and compaction so that a strong bond between these phases is formed. These agents also help reduce the debonding of the two phases that can lead to cracking or pitting during use.
A variety of materials can be used as a plasticizer: the key property is that they alter the consistency of the continuous phase mass, when it is combined with the discontinuous phase.
Oils are particularly useful plasticizers. One useful class of oils is ester oils: oils having at least one ester group in the molecule, especially fatty acid mono and polyesters such as cetyl octanoate, octyl isonanoanate, myristyl lactate, cetyl lactate, isopropyl myristate, myristyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, decyl oleate, cholesterol isostearate, glycerol monostearate, glycerol distearate, glycerol tristearate, alkyl lactate, alkyl citrate and alkyl tartrate; sucrose ester, sorbitol ester, and the like.
Triglycerides and modified triglycerides are particularly useful ester oils. These include vegetable oils such as jojoba, soybean, canola, sunflower, palm, safflower, rice bran, avocado, almond, olive, sesame, persic, castor, coconut, and mink oils. These oils can also be hardened to remove unsaturation and alter their melting points. Synthetic triglycerides can also be. Some modified triglycerides include materials such as ethoxylated and maleated triglyceride derivatives provided. Proprietary ester blends such as those sold by Finetex as Finsolv(copyright) are also suitable, as is ethylhexanoic acid glycerides.
Another type of useful ester oil is liquid polyester formed from the reaction of a dicarboxylic acid and a diol. An example of polyesters suitable for the present invention is the polyesters marketed by ExxonMobil under the trade name PURESYN ESTER(copyright).
A second class of oils suitable for the present invention is hydrocarbon oil. This includes linear and branched oils such as liquid paraffin, squalene, squalane, mineral oil, low viscosity synthetic hydrocarbons such as polyalphaolefin sold by ExxonMobil under the trade name of PureSyn PAO(copyright) and polybutene under the trade name PANALANE(copyright) or INDOPOL(copyright). Highly branched hydrocarbon oils may also be suitable. Although more properly classified as a grease, petrolatum can also serve as a useful plasticizer.
Some natural and synthetic waxes can also be used as plasticers providing they have the correct melting point and solubility properties with the continuous phase.
A third type of material that can function as a plasticizer are C8-C22 fatty acids, preferably C12-C18, preferably saturated, straight-chain fatty acids. However, some unsaturated fatty acids can also be employed. Of course the free fatty acids can be mixtures of shorter (e.g., C10-C14) and longer (e.g., C16-C18) chain fatty acids although it is preferred that longer chain fatty acids predominate over the shorter chain fatty acids.
The fatty acid can be incorporated directly or be generated in-situ by the addition of protic acid. Examples of suitable protic acids include: HCL, adipic acid, citric acid, glycolic acid, acetic acid, formic acid, fumaric acid, lactic acid, malic acid, maleic acid, succinic acid, tartaric acid and polyacrylic acid. Other protic acids are mineral acids such as hydrochloric acids, phosphoric acid, sulfuric acid and the like.
Nonionic surfactants can also serve as plasticizers for the continuous phase. Nonionic surfactant in the context of instant invention are amphiphilic materials in which the polar groups are uncharged. Examples of suitable nonionic surfactants include: ethoxylates (6-25 moles ethylene oxide) of long chain (12-22 carbon atoms) fatty alcohol (ether ethoxylates) and fatty acids; alkyl polyhydroxy amides such as alkyl glucamides; alkyl polyglycosides; esters of fatty acids with polyhydroxy compounds such as glycerol and sorbitol; ethoxylated mon-di-and triglycerides, especially those that have lower melting points; and fatty amides.
Organic bases, especially alkoxy amines like triethanolamine are also useful plasticizers when the surfactant base is soap.
In addition to modulating hardness, the plasticizing agent also helps reduces the consistency of the continuous mass at the extrusion and compaction steps in the process thereby improving the bonding to the discontinuous phase as well as flow around the discontinuous phase at the surface.
Discontinuous Phase
The discontinuous phase comprises from 1 to about 35% of the bar, preferably from 5 to 25%, and most preferably from 10 to 20%. It is generally the shape, distribution and surface quality (e.g., how visually distinctive) of the discontinuous phase that gives the bar an artisan-crafted quality.
The discontinuous phase forms discrete domains in the bar and comprises a water-soluble or water-dispersible matrix and optionally a hardening agent. By water-soluble or water-dispersible is meant the ability of the matrix to disintegrate and disperse when the bar is rubbed against the skin in the presence of water during use. A convenient measure of this property is the intrinsic wear rate the matrix material exhibits under controlled rubbing conditions as described in the Test Methodology section. A suitable matrix should have an intrinsic wear rate between 0.012 and 0.05 gm/cm2, preferably 0.02 to 0.03 gm/cm2, when measured by the Controlled Rubbing Test. Thus, for example material like polyethylene could be used a component of the matrix, e.g., as small beads, but is not suitable by itself as the matrix because its intrinsic wear rate is essentially zero.
The discontinuous phase domains can have a variety of shapes. For example, the domains can appear in cross section to approximate oblate or prolate spheroids, disks, cylinders, prisms, rhomboids, cubes or crescents. They can also have irregular shapes. However, a unifying feature is that their longest dimension be between about 3 and about 75 millimeters in length, preferably 5 to 50 and most preferably between 5 and 35 millimeters.
A key requirement is that the ratio, A, defined as   λ  =            Hardness                    xe2x80x83                  of                    xe2x80x83                  Discontinuous                    xe2x80x83                          Phase                          xe2x80x83                @                  xe2x80x83                                  25          ∘                                  xe2x80x83                          C        .                    Hardness                    xe2x80x83                  of                    xe2x80x83                  Continuous                    xe2x80x83                          Phase                          xe2x80x83                @                  xe2x80x83                                  33          ∘                                  xe2x80x83                          C        .
is greater than 2.0, preferably greater than 2.5, and most preferably greater than 3.0. Here the hardness is measured by the Cylinder Impaction Test described in the Test Methodology section below. There are several methods known in the art to measure the hardness of material like soaps. The Cylinder Impaction Test is a convenient measure in a manufacturing context. However, other measures like the Penetrometer Test described in the Methodology Section can also be employed and the values correlated to the Cylinder Impaction Test. The key point is that the hardness ratio of the two phases measured at temperatures approximating the temperatures of each of the respective phases when they are first brought into contact during the manufacture of the bar be greater than 2. For example, if the discontinuous phase particles and noodles of the continuous phase soap mass are combined in the vacuum chamber of a two stage plodder prior to final extrusion, the hardness of the two phases should differ by at least a factor of two.
It has been found that when this requirement is met, the discontinuous phase can be added as a sufficiently hard solid during high speed extrusion so that it does not undergo excessive deformation and homogenization. It has also been found that this requirement of xcex greater than 2.0, also helps the discontinuous phase to remain prominent at the surface of the bar after stamping without the need for wasteful trimming.
Water-soluble or Water-dispersible Matrix
A key component of the discontinuous phase is a surfactant that is solid at room temperature. The surfactant may be any of those described above in connection with the continuous phase. The surfactant is present in the discontinuous phase at a level between 1 and about 85 Wt %, preferably between 30 and 75 wt %, more preferably 50 and 75%.
A number of surfactants are suitable as a component of the dispersed phase matrix and, as noted above, most of the surfactants described above for the continuous phase can be employed here as well.
Particularly useful matrix surfactants are the sodium, potassium and triethanolamine soaps of long chain (C10-C18) fatty acids, acyl isethionate especially cocoyl isethionate, alkyl taurates, alkyl suflates and sulfonates, alkyl ethoxy sulfates, long chain alkyl ethoxylates, alkylglycosides, fatty acid esters of glycerol and sorbitol, and mixtures thereof.
Another useful matrix forming material is polyalkylene glycol having a melting point above 30xc2x0 C. Preferably, the polyalkylene glycol should have a molecular weight greater than 4,000 to about 100,000, preferably 4000 to 20,000, most preferably 4000-10,000. Minimum MW of about 4000 is believed required so that carrier is solid at room temperature. An especially preferred carrier is polyethylene glycol, for example Carbowax PEG 8000, RTM(copyright) from Union Carbide.
Hydrophobically modified polyalkylene glycol (HMPAG) having broad molecular weight 4,000 to 25,000, preferably 4,000 to 15,000 can also be employed. Generally, the polymers will be selected from polyalkylene glycols chemically and terminally attached by hydrophobic moieties, wherein the hydrophobic moiety can be derivatives of linear or branched alkyl, aryl, alkylaryl, alkylene, acyl (e.g., preferably C8 to C40; fat and oil derivatives of alkylglyceryl, glyceryl, sorbitol, lanolin oil, coconut oil, jojoba oil, castor oil, almond oil, peanut oil, wheat germ oil, rice bran oil, linseed oil, apricot pits oil, walnuts, palm nuts, pistachio nuts, sesame seeds, rapeseed, cade oil, corn oil, peach pit oil, poppyseed oil, pine oil, soybean oil, avocado oil, sunflower seed oil, hazelnut oil, olive oil, grapeseed oil, and safflower oil, Shea butter, babassu oil, etc. The total content of the hydrophobic moiety is preferably 3% wt. to 15% wt. per mole of the defined HMPAG.
Fatty acids, fatty acid esters, and fatty alcohols can be incorporated as part of the matrix forming the discontinuous phase as long as the matrix remains water soluble or water dispersible. Generally, the fatty group has a chainlength between 12 and 22 carbon atoms. Particularly suitable fatty acid esters is glycerol monolaurate.
Still other useful matrix materials in the invention are derived from polysaccarides especially starch. These include unmodified starch; starch modified to alter its water solubility, dispersability, and swelling, and hydrolyzed starch such as maltodextran.
Hardening Agents
As with the continuous phase It is may be possible to tailor the surfactant base of the discontinuous phase so that its hardness falls in the range required to mass-produce by high speed extrusion a multi-phase bar with an artisan crafted appearance. This can be done, for example, by adjusting the titre of the fat charge to achieve a harder mass, e.g., by hydrogenation or by manipulating the water content. However, this can compromise user properties and/or impact cost. Consequently, it is often beneficial to employ a hardening agent in the discontinuous phase.
Polyols and inorganic electrolytes are useful hardening agents when the discontinuous phase is comprised predominantly of fatty acid soaps. Polyols are defined here are molecules having multiple hydroxyl groups. Preferred polyols include glycerol, propylene glycol, sorbitol, and polyvinyl alcohol.
Preferred inorganic electrolytes include monovalent chloride salts, especially sodium chloride; monovalent and divalent sulfate salts like sodium sulfate; sodium carbonate; monovalent aluminate salts, monovalent phosphates, phosphonates, polyphosphate salts; and mixtures thereof. Further, the bar composition of the invention may include 0 to 25% by weight of crystalline or amorphous aluminium hydroxide. The said aluminium hydroxide can be generated in-situ by reacting fatty acids and/or non-fatty mono- or polycarboxylic acids with sodium aluminate, or can be prepared separately by reacting fatty acids and/or non-fatty mono- or polycarboxylic acids with sodium aluminate and adding the reaction product to the soap.
Another class of hardening agents are insoluble inorganic or mineral solids that can structure the discontinuous phase by network formation or space-filling. These include fumed, precipitated or modified silica, alumina, calcium carbonate, kaolin, and talc. Alumino-silicate clays especially synthetic or natural hectorites can also be used.
Optional Ingredients
In addition to the ingredients described above, the bar can also contain a variety of optional ingredients used to increase its shelf life, aesthetics or functionality. The ingredients can be found in continuous or discontinuous phase. These include chelating agents such as EDTA, preservatives like dimethyloldimethylhydantoin (Glydant XL1000), parabens, sorbic acid antioxidants such as, for example, butylated hydroxytoluene (BHT) and a variety of natural and synthetic perfume components. Particularly useful optional ingredients are skin benefit agents used to deliver some useful end benefit to the skin and optical modifies used to confer a unique appearance to the bar.
Skin Benefit Agents
The first class of ingredients are nutrients used to moisturize and strengthen the skin. These include:
a) vitamins such as vitamin A and E, and vitamin alkyl esters such as vitamin C alkyl esters;
b) lipids such as cholesterol, cholesterol esters, lanolin, cerimees, sucrose esters, and pseudo-ceramides;
c) Liposome forming materials such as phospholipids, and suitable amphiphilic molecules having two long hydrocarbon chains;
d) essential fatty acids, poly unsaturated fatty acids, and sources of these materials;
e) triglygerides of unsaturated fatty acids such as sunflower oil, primrose oil avocado oil, almond oil;
f) vegetable butters formed from mixtures of saturated and unsaturared fatty acids such as Shea butter;
g) mineral such as sources of zinc, magnesium, and iron;
A second type of skin benefit agent is a skin condition used to provide a moisturized feel to the skin. Suitable skin conditioners include:
a) silicone oils, gums and modifications thereof such as linear and cyclic polydimethylsiloxanes, amino, alkyl, and alkylaryl silicone oils;
b) hydrocarbons such as liquid paraffins, petrolatum, vaseline, microsrystalline wax, ceresin, squalene, pristan, paraffin wax and mineral oil;
c) conditioning proteins such as milk proteins, silk proteins and glutens;
d) cationic polymers as conditioners which may be used include Quatrisoft LM-200 Polyquatemium-24, Merquat Plus 3330xe2x80x94Polyquaternium 39; and Jaguar(copyright) type conditioners.
e) Humectants such as glycerol, sorbitol, and urea
f) Emmolients such as esters of long chain fatty acids, such as isopropyl palmitate and certyl lactate;
A third type of benefit agent is deep cleansing agents. These are defined here as ingredients that can either increase the sense of refreshment immediately after cleansing or can provide a sustained effect on skin problems that are associated with incomplete cleansing. Deep cleansing agents include:
a) antimicrobials such as 2-hydrozy4,2xe2x80x2,4xe2x80x2-trichlorodiphenylether (DP300) 2,6-dimethyl-4-hydroxychlorobenzene (PCMX), 3,4,4xe2x80x2-trichlorocarbanilide (TCC), 3-trifluoromethyl-4,4xe2x80x2-dichlorocarbanilide (TFC), benzoyl peroxide, zinc salts, tea tree oil,
b) anti-acne agents such as salicylic acid, lactic acid, glycolic acid, and citric acid, and benzoyl peroxide (also an antimicrobial agent),
c) oil control agents including sebum suppressants, mattifiers such as silica, titanium dioxide, oil absorbers, such as microsponges,
d) astringents including tannins, zinc and aluminum salts, plant extracts such as from green tea and Witchhazel (Hammailes),
e) scrub and exfoliating particles, such as polyethylene spheres, agglomerated silica, sugar, ground pits, seeds, and husks such as from walnuts, peach, avocado, and oats, salts,
f) cooling agents such as menthol and its various derivatives and lower alcohols
g) fruit and herbal extracts
h) skin calming agents such as aloe vera
i) essential oils such as mentha, jasmine, camphor, white cedar, bitter orange peel, ryu, turpentine, cinnamon, bergamot, citrus unshiu, calamus, pine, lavender, bay, clove, hiba, eucalyptus, lemon, starflower, thyme, peppermint, rose, sage, methol, cineole, sugenol, citral, citronelle, borneol, linalol, geranoil, evening primrose, camphor, tymol, spirantol, penene, linonene and terpenoid oils;
Other benefit agents that can be employed include antiageing compounds, sunscreens, and skin lightening agents.
When the benefit agent is oil, especially low viscosity oil, it may be advantageous to pre-thicken it to enhance its delivery. In such cases, hydrophobic polymers of the type described in U.S. Pat. No. 5,817,609 to He et al may be employed, which is incorporated by reference into the subject application.
The benefit agent generally comprises about 0-25% by wt. of the composition, preferably 5-20%, and most preferably between 2 and 10%. Although the benefit agent can be added to either phase of the bar, in some cases it is especially desired to add the benefit agent to the discontinuous phase.
A final group of optional ingredients is optical modifiers which are defined as materials that modify the optical texture or transparency of the phases or introduce a pattern to increase the distinctiveness of one or both of the phases. Examples of suitable optical modifiers include:
a) transparency enhancing solvents such as glycerol, propylene glycol, sorbitol, or triethanolamine,
b) speckles/bits such as ground fruit pits, seeds, polyethylene beads, mineral agglomerates, and loofha,
c) reflective plate-like particles such as mica,
d) pearlizing agents such as coated micas, and certain waxes
e) wax/plastic slivers that resemble for example fruits slices,
f) Vegetable or fruit slivers
g) mattefiers such as TiO2
h) mixtures of the above
Further, either the continuous or phase can be made multicolored, e.g., striped, through the judicious use of dye as is well known in the art.
Bar Properties
In addition to the ratio of hardness of continuous phase to discontinuous phase, xcex, described about, it is also critical to the invention that the bar have a descriptive visual scoring of at least 3.0 measured by a visual discrimination panel test as defined below:
The bars of the invention also preferably should have a certain plasticity. This is defined such that the continuous phase has a plastic radius measured in a three-point test for plasticity or brittleness also described below. The plastic radius of the continuous phase should be greater than 2 mm, preferably greater than 2.5 when measured at temperature of 40xc2x0 C. in this test.
Test Methodology
Bar Hardness
A variety of methods are known in the art to measure the hardness of soft solids such as toilet soaps. Two techniques have been used here, the Cylinder Impaction Test which measures the maximum force before yielding and the Penetration Test which measures the penetration of a needle under a constant load. Although the invention is described by parameters that measured by the Cylinder Impaction Test, this was done for convenience from a manufacturing perspective. The various hardness tests can obviously be inter-correlated.
Cylinder Inpaction Test for Hardness
The hardness of the continuous and dispersed phase was measured on extruded and compacted samples using the Cylinder Impaction Test employing a modified Crush-Test protocol that is used for measuring carton strength. A Regmed Crush Tester was employed.
Samples (typically 8xc3x975xc3x972 cm) at the desired temperature were placed on the lower plate of the tester fitted with a pressure gauge and a temperature probe inserted in the sample approximately 4 cm from the test area. An 89 gm inox metalic cylander (2.2 cm in diameter (0.784 in) and 3 cm in length (1.18 in)) was placed at a central location on the top of the sample. The upper plate was then lowered to just touch cylinder.
The top plate was then lowered at a programmed rate of 0.635xc2x10.13 mm/s (0.025xc2x10.005 in/s). At a certain strain, the sample will yield, bend or fracture and the maximum force expressed as PSI (lbs/inch2) and average sample temperature are recorded. The water content of the sample was measured immediately after the test by microwave analysis. The hardness measurement was repeated a total of 3 times with fresh samples and an average taken. It is important to control the temperature and water content of the sample since hardness is sensitive to both these variables.
Penetration Test
A model PNR 10 penetrometer manufactured by FUR Berlin was employed. Three standard cones (needles) are available: 2.5 g (18-0063), diameter: 0.9-3.5 mm, length: 79 mm. The measurement was carried out as follows: The cone is moved nearer to the surface of the test mass at the desired temperature with the coarse cone adjustment knob then moved to just touch the surface of the test material with the fine cone adjustment knob. The start button is then pressed, releasing the conexe2x80x94weighing 100 g for a time period of 60 sec at which time the penetration distance the cone travels in the sample is measured and shown on a displacement gauge display. The reset button is pressed and the cone is lifted back to its zero position.
Three-Point Bend Test for Plasticity or Brittleness
The plastic zone radius or plasticity (brittleness) of the continuous and dispersed phase was measured using the standard Three-Point Bend Test. The Instron 5567 Material testing machine with the three-point bend rig attachment was used to obtain force and displacement data. The three-point bend test rig, mounted on the Instron 5567 machine, consisted of a hemispherical indenter and two static hemispherical supports. The span distance between the support was 6 inches.
Three types of three-point bend test measurements were needed for each sample in order to obtain the plasticity: un-notched bar, notched bar, and indentation tests.
Extruded soap samples were wrapped in plastic and equilibrated at 40xc2x0 C. in an oven overnight. They were then placed one by one upon the static supports. For the un-notched test, the indenter was set in a position above the sample and then set automatically in motion at a 5 mm/min speed.
The notched test was carried out the same way, except that a notch was cut in the underside of the sample opposite to the indenter. For the indentation test, the soap sample was placed on a flat surface and the indentation bar was lowered at a 1 mm/min speed. The test was stopped when the force exceeded the peak force obtained from the un-notched test. Force and displacement data for the three tests were recorded in triplicates on a PC for further analysis and parameter computation. The plastic zone radius, r, provides the desired measure of plasticity and was calculated using Irwin""s analysis. This may be found in T. L. Anderson""s treatise xe2x80x9cFracture Mechanics Fundamentals and Applicationxe2x80x9d, pages 72-99, CRC Press (Boca Raton, Fla., 1995) and a copy of this is being incorporated by reference into the subject application
It is desirable that the plastic radius of the continuous phase be greater than 2.0 cm, preferably greater than 2.5 cm, and most preferable greater than 3 cm.
Controlled Rubbing Test
The intrinsic wear rate of the discontinuous phase is measured by the following procedure.
a) Prepare a sample of discontinuous phase of the approximate dimensions: 7.5 cm longxc3x975.5 cm widexc3x972.3 cm thick
b) Measure and record the surface area of the face of each sample in square cm.
c) Record the weight of each bar prior to being washed.
d) Adjust the faucet water to 105xc2x0 F. (40xc2x0 C.) and keep it running into a vessle.
e) Immerse the bar and hands into the vessle.
f) Remove the bar from the water and rotate twenty (20) half turns.
g) Repeat steps d-f.
h) Immerse the bar for a third time and place into a soap dish.
i) Add 7.5 ml of water to the soap dish.
j) Repeat the wash procedure (steps c-g) three additional times during the first day. The washes should be spaced evenly throughout the work day.
k) After the last wash of the day, add 7.5 ml of water to the soap dish and let the bar sit overnight.
l) The following morning repeat the wash procedure (steps ii through vi) then place the bar sideways on a drying rack.
m) Allow the bar to sit for 24 hours then weigh the bar to the nearest 0.01 gm.
The results are expressed as the accumulated weight loss divided by the surface area of the face.
Soap Transparency Test
The degree of transparency was measured using a light transmission tester model EVT 150 manufactured by DMSxe2x80x94Instrumentacao Cientifica Ltd. The instrument consists of a light source providing a 1.5 cm circular beam, a detector fitted to an analog meter, and a sample holder. The measurement procedure is as follows.
The instrument is first set to 100% transmission in air (i.e., without a test sample). The test sample of the bar material, approximately 90 g, having a thickness of 3 cm is placed in the sample chamber and the % transmission relative to air is measured. Normal opaque soap bars have 0% transmission, while translucent bars have a transmission ranging from about 5 to about 40%. Highly transparent bars such as those made by melt-cast processes have a transmission generally greater than 45%.
It has been found that discontinuous phase compositions having a % transmission difference relative to the continuous phase of greater than about 5% are perceived as visually distinctive. Preferably, the difference in light transmission between the phases should be greater than 10%.
Visual Discrimination Panel Test
Five bar samples taken at different times in a single test run are placed on a neutral gray background in a conventional viewing box. Above the test samples are placed high quality color photographs of xe2x80x9cstandard barsxe2x80x9d that are agreed by a panel of five experts represent each xe2x80x9cgradexe2x80x9d in the following 5-point descriptive visual grading scale:
Descriptive Visual Grading Scale
1xe2x80x94poor: 2 phases not discernable
2xe2x80x94ordinary: smeared non-distinct boundary, some fine striations
3xe2x80x94above average: 2 phases evident but some smearing and loss of contrast
4xe2x80x94very good: 2 phases evident, sharp contrast but slight smearing at phase boundary
5xe2x80x94excellent: 2 phases evident, sharp contrast with little or no smearing
10 panelists (mix of expert and naive) evaluated the set of five samples and assigned a forced choice integer grade. They were instructed to mentally integrate overall surface appearance, quality and distinctiveness of the set in assigning a single grade. For each set of 5 bars, the average value across panelists is taken.
Bar Manufacture
The continuous soap phase is produced in standard toilet soaps finishing line using processing techniques and equipment well known in the art.
The first step of this process involves the mixing of dried soap noodles from the storage silos with the minor ingredients in a batch mixer. The objective of this operation is to generate a good distribution of the minor ingredients throughout the bulk of the soap batch until uniform coating of the noodles has occurred.
After mixing, the soap mass is generally passed through a refiner followed by a roll mill to achieve micro-mixing and improve composition uniformity.
Finally the soap will be further refined and plodded, usually under vacuum in a two-stage operation with a single or twin worm configuration with an intermediate vacuum chamber, and extruded as a bar for cutting and stamping. Both the final refiner and plodder stages play a part in completing the total mixing process by providing additional micro-mixing.
The discontinuous phase can also be produced as noodles in a conventional toilet bar making equipment but with a different composition than the continuous phase adequate to meet the hardness requirements.
The discontinuous phase is typically stored in for example, a buffer hopper, generally at 25xc2x0 C. After suitable tempering it is combined with (e.g., added onto) the continuous soap phase which is at a temperature between 33xc2x0 and 50xc2x0 C., preferably 33xc2x0 and 42xc2x0 C., typically, in the vacuum chamber, between the refining and extrusion stages, by means of dosing equipment which controls its rate of delivery. For this purpose, the vacuum chamber is modified to receive the discontinuous soap phase stream.
The composite mass, (i.e., combining of continuous and discontinuous phase masses) is then compacted and extruded into billets which are then cut and stamped into the desired shape.
If done under vacuum, the vacuum is typically applied during mixing and refining, until the combined masses are extruded through, for example, a nosecone. Typically, the vacuum is at 500 to 600 mm pressure (measured as mercury or Hg pressure).
Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts or ratios of materials or conditions or reaction, physical properties of materials and or use are to be understood as modified by the word xe2x80x9caboutxe2x80x9d.
Where used in the specification, the term xe2x80x9ccomprisingxe2x80x9d is intended to include the presence of stated features, integers, steps, components, but not to preclude the presence or addition of one or more features, integers, steps, components or groups thereof.
The following examples are intended to further illustrate the invention and are not intended to limit the invention in any way.
All percentage used, unless indicated otherwise, are intended to be percentages by weight.

Methods of cleansing, moisturizing and refreshing using multiphase bars having artisan-crafted appearance

Unilever Home and Personal Care USA, division of Conopco, Inc.


The invention relates to dendrimeric fullerene derivatives in which the fullerene is linked to at least one dendron, wherein the or each dendron has at least one protic group which imparts water solubility.

The invention relates to dendrimeric fullerene derivatives, that is fullerene derivatives which are substituted by one or more dendrons. Fullerenes are carbon compounds of the formula C2(10+m), where m is a natural number. They contain twelve five-membered and any desired number, i.e. m, but at least two, six-membered rings of carbon atoms.
The outwardly vaulted surface of fullerenes and the alignment of the xcfx80 electrons produced thereby cause a great reactivity to free radicals /1/ (The literature references are listed at the end of the description). Thus, it is known for C60 Buckminsterfullerene that it very easily adds radicals. The absorption of up to 34 methyl radicals is described and the name xe2x80x9cradical spongexe2x80x9d has been proposed therefor /1/.
It is known that hydroxyl and hydroperoxide radicals in biological systems preferably attack polyunsaturated fatty acids. This attack brings about crosslinking and polymerization of the fatty acid structures. Free radicals thus also bring about damage to biomembranes, in particular the membranes of nerve cells, which are distinguished by a particularly high proportion of unsaturated fatty acids in their lipids. As a result of the change in the lipid structure of such biomembranes, a change in the membrane permeabilities, a change in their transport functions, a change in their barrier mechanisms and changes in their receptor activities can occur and this can lead to the death of the nerve cells. Overstimulation of glutamate receptors likewise led to the formation of free oxygen radicals and nitric oxide radicals /2-6/ and as a result to damage to nerve cells and to the occurrence of specific syndromes /7-10/.
Radical scavengers provide for the removal of harmful free radicals, act as antioxidants and suppress the damage to the nerve cells and the loss of function of neuromembranes. Therefore, especially fullerenes with their excellent radical-scavenging properties should act as neuroprotectants and should be able to be employed for the protection of biological membranes against oxidative changes. C60 fullerene, however, is only soluble in very few organic solvents, such as benzene and toluene, and thus cannot also be administered to biological membranes. The addition of suitable functional groups on C60, however, should improve the water solubility and thus also make possible use as antioxidants in biological systems. The first positive results were achieved using polyhydroxylated C60/11/, and trisubstituted synthetic malonic acid derivatives C60[C(COOH)2]3, which had both in vitro and in vivo neuroprotective activities, afforded better results /12/. The preparation of the two isomers having C3 or D3 symmetry described in /12/ was carried out by the method of Hirsch /13/ by triple cyclopropanylation of C60 with diethyl malonate, hydrolysis and subsequent chromatographic purification. The two test compounds exhibited strong affinity for free radicals, as it was possible to show by EPR spectroscopy, and inhibited the excitotoxic death of cell cultures of cortical neurons which were induced by N-methyl-D-aspartate (NMDA) exposure, by xcex1-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) exposure or by oxygen/glucose withdrawal. The C3-symmetrical derivative moreover reduced apoptotic neural death which was induced either by serum withdrawal or exposure of Axcex21-42 protein. In all cases, the C3 regioisomer exhibited greater efficacy than the D3 isomer, which can be attributed to the greater polarity and thus improved ability of lipid membrane penetration /12/.
Relative to the polyhydroxy-substituted fullerenes, the malonic acid derivatives exhibited better activity as radical scavengers as it [lacuna] with the lower degree of addition and resulting from this an improved provision of a relatively large reactive surface with, at the same time, accompanying improved water solubility.
Furthermore, fullerenes are known from /17/ which are linked to poly(benzyl ether) dendrons. These fullerene derivatives, however, are insoluble in water. In /19/, dendrimeric fullerenes are likewise disclosed which are insoluble in water.
In relation to this prior art, the invention was based on the object of further improving the water solubility of fullerenes or fullerene derivatives without at the same time, as in the cases known to date, making smaller or screening off the reactive C60 surface and thus reducing the radical-scavenging properties.
This object is achieved according to the invention by dendrimeric fullerene derivatives in which the fullerene is linked to at least one dendron, wherein the or each dendron has at least one protic group which imparts water solubility.
Another object of the invention further relates to an agent comprising the inventive fullerene for thereapeutic purposes. The invention additionally relates to an agent comprising the inventive fullerene as neuroprotectant. The inventive fullerene derivates can be used in the production of pharmaceuticals for the treatment of diseases in which free radicals have a harmful effect on the organism to be treated.
Suitable protic groups are the hydrophilic groups known to the person skilled in the art, preferably xe2x80x94OH, xe2x80x94COOH, xe2x80x94NH2, xe2x80x94SO3H, xe2x80x94PO3H, NR4+, xe2x80x94NHOH, or xe2x80x94SO2NH2, where the four radicals R independently of one another can in each case identically or differently be xe2x80x94H, alkyl or aryl. xe2x80x94OH, xe2x80x94COOH and xe2x80x94NH2 are particularly preferred. The group xe2x80x94COH can also be employed.
The water solubility of the fullerene derivatives according to the invention can be greater than 1 mg/ml at 25xc2x0 C. and pH 7, preferably greater than 5 mg/ml, particularly preferably greater than 10 g/l and very particularly preferably greater than 20 mg/ml. At 25xc2x0 C. and pH 10 it can be greater than 10 mg/ml, preferably greater than 50 mg/ml, particularly preferably greater than 100 g/l and very particularly preferably greater than 200 mg/ml.
A dendron within the meaning of the invention is an addendum of the C60 nucleus unit which has a branching at the end as a structural unit. Again, in each case the same or another subunit, at whose other end a branching is likewise located in turn, can be linked to this. Depending on the degree of branching, the number of the nearest branchings and thus also the number of functional (and water-soluble) end groups is thus doubled, tripled or multiplied. Each radially symmetrical xe2x80x9cshellxe2x80x9d formed by repeated linkage of dendrons is designated as the next generation. In order to make available more reactive surface for radicals, it appears sensible to keep the dendrons necessary for the water solubility at as far a distance as possible from the C60 core in order to prevent its xe2x80x9ccoveringxe2x80x9d. This is possible by binding of the dendrons of the first generation via a so-called xe2x80x9cspacerxe2x80x9d, i.e. a carbon chain of length C1 up to about C100, preferably C2-C10, which serves the 1st generation as a xe2x80x9cseparatorxe2x80x9d.
Suitable branchings are especially trivalent or polyvalent elements such as, for example, N-, C-, P-, Si, or polyvalent molecular segments such as aryl-, heteroaryl. The degree of branching is preferably between two and three and the number of generations can be between 1 and 10 inclusive.
Preferred solutions to the object according to the invention follow from the subclaims. Individual features or a number of the features disclosed in the subclaims can also in each case represent solutions to the underlying object per se or in combination and the individual features can also be combined in any desired manner within the claim categories.
In relation to the examples mentioned further above, monoadducts of fullerenes should be an improvement if their water solubility is adequately high. The lower the degree of addition of the fullerenes, the greater their free reactive surface will be, which appears responsible for the radical-scavenging properties. Such monoadducts, however, should have a lower water solubility in relation to polyadducts, as the number of hydrophilic groups decreases correspondingly. This conflict is solved by the fullerenes according to the invention as they in turn arbitrarily increase in water solubility owing to the branchings of the higher generations lying further outside.
A preferred compound is shown in formula 1 (Scheme 1). What are concerned here are dendrimer-branched derivatives of C60-fullerenes. Monosubstituted dendrimers of this type offer the advantage that they retain their excellent water solubility independently of the degree of addition owing to the choice of suitable functional end groups. The number of the functions of the outermost dendrimer shell contributing to the solubility is additionally specified by the degree of branching and by the number of dendron generations (cf. section above). Branching elements of the individual molecular esters can inter alia preferably be xcex3-amino-triscarboxylic acids of the type shown in formula 1, xcex1-aminodicarboxylic acids, xcex1-xcfx89-diaminocarboxylic acids, hydroxycarboxylic acids, tartaric acid derivatives, polyphenols, carbohydrate components of the pentose and hexose type, glycerol derivatives and also generally polyfunctional compounds. The consecutive linkages of the individual dendrimer branches or of the individual generations then corresponds to acid amide compounds, peptide compounds, ester bonds, depsipeptide-like bonds according to the nature of the variable acid amide or ester linkage of amino acids and hydroxy acids, glyceride-like bonds and polyesters or polyethers, polyphenyl ethers and glycosides. An adverse effect of the free fullerene surface due to screening is only expected in the case of dendrimer shells of the third generation, screening on account of easy penetrability of small free radicals, nevertheless does not necessarily have to lead to a decrease in the antioxidant activity. Owing to the choice of suitable lengths of two up to six carbon atoms in the spacer chains, the availability of the fullerene surface can additionally be varied or guaranteed. The use of long fatty acid chains in the individual branches can additionally bring about an affinity for the fatty acid chains of the lipids within the membrane bilayer and thus improved intercalation in nerve membranes and improved radical-scavenging properties.
The preparation of the target compounds is carried out by convergent synthesis, i.e. the corresponding dendrimer branch is synthesized separately up to the first, second, third or nth generation and only finally bonded to C60 fullerene by means of a suitable linkage reaction, such as, for example, a cyclopropanylation, Diels-Alder reaction, [3+2] cycloaddition and the like. For the synthesis of the fullerene dendrimer of the first generation (cf. preparation example 8) according to Scheme 2, the O-benzyl-protected xcex3-hydroxybutyric acid 2 is condensed with the carboxy-protected xcex3-aminotriscarboxylic acid [Behera amine, di-t-butyl 4-amino4-(2-t-butyloxycarbonylethyl)heptanedioate 3 (/14/, /15/, /18/) by reaction with condensing agents and activators such as, for example, dicyclohexyl-carbodiimide [DCD], 1-hydroxybenzotriazole [1-OH-BT], but also other carbodiimides, N-hydroxy compounds, and the like. The acid amide [di-t-butyl 4-(4-benzyloxybutyrylamino)4-(2-t-butyloxycarbonylethyl)heptane-dioate 4] resulting therefrom can be deprotected by hydrogenolysis or specific, gentle hydrolysis to give the free hydroxy acid amide [di-t-butyl 4-(4-hydroxybutyrylamino)-4-(2-t-butyloxycarbonylethyl)heptanedioate 5] without affecting the protective groups of the carboxyl functions in the course of this. The following reaction of 5 with malonyl dichloride and pyridine or other nitrogen bases leads to the dendron 6 of the first generation [nomenclature for cascade polymers: 6-cascade:methane[2]:(2-aza-7-oxa-3,8-dioxooctylidyne):tert-butyl propanoate], which is a dialkyl malonate ester with amide-like dendron linkage and a C4-long spacer chain between the branching unit and the malonate residue. Correspondingly, by choice of other benzyl-protected xcfx89-hydroxycarboxylic acids 2 such as, for example, 3-hydroxypropionic acid, 5-hydroxyvaleric acid or 6-hydroxyhexanoic acid, the spacer chain can also be shortened or lengthened in any desired manner. According to a process described by us /16/, C60 can then be cyclopropanylated in the presence of CBr4 and DBU/methylene chloride using synthon 6. The tert-butyl protective groups ofthe resulting
dendrimer fullerene [6-cascade:methano-C60-fullerene[2]:(2-aza-7-oxa-3,8-dioxooctylidyne):tert-butyl propanoate 7] can be easily removed by hydrolysis, preferably using formic acid, so that the polycarboxy-functionalized dendrimer fullerene 8 which is water-soluble and can be employed as a neuroprotectant is formed. [6-Cascade:methano-C60-fullerene[2]:(2-aza-7-oxa-3,8-dioxooctylidyne):propanoic acid.
The dendrimer fullerene 1 of second generation [18-cascade:methano-C60-fullerene[2]:(2-aza-7-oxa-3,8-dioxooctylidyne):(2-aza-3-oxopentylidyne):propanoic acid] (cf. preparation example 1) is prepared (Scheme 3) analogously to the synthesis of the derivative of first generation 8 shown in Scheme 2. As in the first case, the tert-butyl-protected xcex3-aminotriscarboxylic acid 3 is reacted with the appropriate nitrotriscarboxylic acid 9, whose tert-butyl ester is the synthesis precursor of 3 (15, 16), using DCC in the presence of 1HO-BT and subsequent reduction with hydrogen to the dendron 10 of second generation [9-cascade:aminomethane[3]:(2-aza-3-oxopentylidyne):tert-butyl propanoate]. The analogous reactions as for the preparation of 8 lead to linkage with the spacer 2, formation of the corresponding malonic acid diester and cyclopropanylation to give a carboxyl-protected dendrimer fullerene derivative. The analogous removal of the protective groups leads to the dendrimer fullerene 1 of the second generation. The latter is already very readily soluble in water (pH  greater than 7), MeOH and other polar solvents. In water, a solubility of about 34 mg/ml at 25xc2x0 C. and pH 7 was measured for the compound mentioned. The solubility at pH 10 was about 250 mg/ml.
A third condensation reaction between the amino derivative 10 and the nitrotriscarboxylic acid 9 leads to a dendron 11 of the third generation [27-cascade:aminomethane[3]:(2-aza-3-oxopentylidyne)2:tert-butyl propanoate], which in turn can be converted by spacer lengthening into the cyclopropanylation reagent 12 of the third generation. Addition to fullerene C60 under the conditions already described yields a dendrimer 13 of the third generation having a C60 as core unit. Deprotection of the tert-butyl groups in turn yields a water-soluble dendrimer fullerene [54-cascade:methanofullerene[2]:(2-aza-7-oxa-3,8-dioxooctylidyne):(2-aza-3-oxopentylidyne)2:propanoic acid 14] (Scheme 4) of the third generation, which should be distinguished by radical-scavenging properties and should have membrane-protective and neuroprotective properties.

Dendrimeric fullerene derivatives, process for their preparation, and use as neuroprotectants