This invention provides non-immunosuppressive rapamycin dialdehydes, which are useful as neurotrophic agents, in the treatment of solid tumors, and vascular disease.

This invention relates to non-immunosuppressive rapamycin dialdehydes, which are useful as neurotrophic agents, in the treatment of solid tumors, and hyperproliferative vascular disease.
Rapamycin is a macrocyclic triene antibiotic produced by Streptomyces hygroscopicus, which was found to have antifungal activity, particularly against Candida albicans, both in vitro and in vivo [C. Vezina et al., J. Antibiot. 28, 721 (1975); S. N. Sehgal et al., J. Antibiot. 28, 727 (1975); H. A. Baker et al., J. Antibiot. 31, 539 (1978); U.S. Pat. No. 3,929,992; and U.S. Pat. No. 3,993,749]. Additionally, rapamycin alone (U.S. Pat. No. 4,885,171) or in combination with picibanil (U.S. Pat. No. 4,401,653) has been shown to have antitumor activity.
The immunosuppressive effects of rapamycin have been disclosed in FASEB 3, 3411 (1989). Cyclosporin A and FK-506, other macrocyclic molecules, also have been shown to be effective as immunosuppressive agents, therefore useful in preventing transplant rejection [FASEB 3, 3411 (1989); FASEB 3, 5256 (1989); R. Y. Calne et al, Lancet 1183 (1978); and U.S. Pat. No. 5,100,899]. R. Martel et al. [Can. J. Physiol. Pharmacol. 55, 48 (1977)] disclosed that rapamycin is effective in the experimental allergic encephalomyelitis model, a model for multiple sclerosis; in the adjuvant arthritis model, a model for rheumatoid arthritis; and effectively inhibited the formation of IgE-like antibodies. FK-506 and some synthetic FKBP-12 binding ligands have been shown to be neuroprotective and neuroregenerative [U.S. Pat. No. 5,696,135, U.S. Pat. No. 5,721,256, U.S. Pat. No. 5,780,484, U.S. Pat. No. 5,811,434 and U.S. Pat. No. 5,840,736].
Rapamycin is also useful in preventing or treating systemic lupus erythematosus [U.S. Pat. No. 5,078,999], pulmonary inflammation [U.S. Pat. No. 5,080,899], insulin dependent diabetes mellitus [U.S. Pat. No. 5,321,009], skin disorders, such as psoriasis [U.S. Pat. No. 5,286,730], bowel disorders [U.S. Pat. No. 5,286,731], smooth muscle cell proliferation and intimal thickening following vascular injury [U.S. Pat. Nos. 5,288,711 and 5,516,781], adult T-cell leukemia/lymphoma [European Patent Application 525,960 A1], ocular inflammation [U.S. Pat. No. 5,387,589], malignant carcinomas [U.S. Pat. No. 5,206,018], cardiac inflammatory disease [U.S. Pat. No. 5,496,832], anemia [U.S. Pat. No. 5,561,138] and increase neurite outgrowth [Parker, E. M. et al, Neuropharmacology 39, 1913-1919, 2000].
A rapamycin ester, rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid [disclosed in U.S. Pat. No. 5,362,718], also known as CCI-779, has been shown to have antitumor activity against a variety of tumor cell lines, in in vivo animal tumor models, and in Phase I clinical trials. [Gibbons, J., Proc. Am. Assoc. Can. Res. 40: 301 (1999); Geoerger, B., Proc. Am. Assoc. Can. Res. 40: 603 (1999); Alexandre, J., Proc. Am. Assoc. Can. Res. 40: 613 (1999); and Alexandre, J., Clin. Cancer. Res. 5 (November Supp.): Abstr. 7 (1999)].
This invention provides non-immunosuppressive rapamycin dialdehydes, and methods of using them that are described herein. As defined herein, the term xe2x80x9ca rapamycin dialdehydexe2x80x9d defines a class of neurotrophic compounds which contain the basic rapamycin dialdehyde nucleus (shown below). These compounds lack the immunosuppressive properties associated with an intact rapamycin nucleus. The rapamycin dialdehydes of this invention include compounds which may be chemically or biologically modified as derivatives of the rapamycin dialdehyde nucleus, while still retaining neutrophic properties. Accordingly, the term xe2x80x9ca rapamycin dialdehydexe2x80x9d includes esters, ethers, oximes, hydrazones, and hydroxylamines of rapamycin, as well as rapamycin dialdehydes in which functional groups on the rapamycin dialdehyde nucleus have been modified, for example through reduction or oxidation. The term xe2x80x9ca rapamycin dialdehydexe2x80x9d also includes pharmaceutically acceptable salts of rapamycin dialdehydes, which are capable of forming such salts, either by virtue of containing an acidic or basic moiety.
It is preferred that the esters and ethers of rapamycin dialdehyde are of the hydroxyl groups at the 42- and/or 31-positions of the rapamycin dialdehyde nucleus, esters and ethers of a hydroxyl group at the 27-position (following chemical reduction of the 27-ketone), and that the oximes, hydrazones, and hydroxylamines are of a ketone at the 42-position (following oxidation of the 42-hydroxyl group) and of 27-ketone of the rapamycin dialdehyde nucleus.
Preferred 42- and/or 31-esters and ethers of rapamycin, which serve as starting materials for the corresponding rapamycin dialdehydes, are disclosed in the following patents, which are all hereby incorporated by reference: alkyl esters (U.S. Pat. No. 4,316,885); aminoalkyl esters (U.S. Pat. No. 4,650,803); fluorinated esters (U.S. Pat. No. 5,100,883); amide esters (U.S. Pat. No. 5,118,677); carbamate esters (U.S. Pat. No. 5,118,678); silyl ethers (U.S. Pat. No. 5,120,842); aminoesters (U.S. Pat. No. 5,130,307); acetals (U.S. Pat. No. 5,51,413); aminodiesters (U.S. Pat. No. 5,162,333); sulfonate and sulfate esters (U.S. Pat. No. 5,177,203); esters (U.S. Pat. No. 5,221,670); alkoxyesters (U.S. Pat. No. 5,233,036); O-aryl, -alkyl, -alkenyl, and -alkynyl ethers (U.S. Pat. No. 5,258,389); carbonate esters (U.S. Pat. No. 5,260,300); arylcarbonyl and alkoxycarbonyl carbamates (U.S. Pat. No. 5,262,423); carbamates (U.S. Pat. No. 5,302,584); hydroxyesters (U.S. Pat. No. 5,362,718); hindered esters (U.S. Pat. No. 5,385,908); heterocyclic esters (U.S. Pat. No. 5,385,909); gem-disubstituted esters (U.S. Pat. No. 5,385,910); amino alkanoic esters (U.S. Pat. No. 5,389,639); phosphorylcarbamate esters (U.S. Pat. No. 5,391,730); carbamate esters (U.S. Pat. No. 5,411,967); carbamate esters (U.S. Pat. No. 5,434,260); amidino carbamate esters (U.S. Pat. No. 5,463,048); carbamate esters (U.S. Pat. No. 5,480,988); carbamate esters (U.S. Pat. No. 5,480,989); carbamate esters (U.S. Pat. No. 5,489,680); hindered N-oxide esters (U.S. Pat. No. 5,491,231); biotin esters (U.S. Pat. No. 5,504,091); O-alkyl ethers (U.S. Pat. No. 5,665,772); and PEG esters of rapamycin (U.S. Pat. No. 5,780,462). The preparation of these esters and ethers are disclosed in the patents listed above. The preparation of the corresponding esters and ethers of rapamycin dialdehyde can be accomplished using the methodology described in these patents, starting with rapamycin, followed by the ring opening reactions described herein. An improved synthesis of 42-esters and ethers of rapamycin is disclosed in U.S. Pat. No. 6,277,539, which is hereby incorporated by reference.
Preferred 27-esters and ethers of rapamycin, which serve as starting materials for the corresponding rapamycin dialdehydes, are disclosed in U.S. Pat. No. 5,256,790, which is hereby incorporated by reference. The preparation of these esters and ethers are disclosed in the patents listed above. The preparation of the corresponding esters and ethers of rapamycin dialdehyde can be accomplished using the methodology described in these patents, starting with rapamycin, followed by the ring opening reactions described herein.
Preferred oximes, hydrazones, and hydroxylamines of rapamycin are disclosed in U.S. Pat. Nos. 5,373,014, 5,378,836, 5,023,263, 5,023,264, and 5,563,145, which are hereby incorporated by reference. The preparation of these oximes, hydrazones, and hydroxylamines, which serve as starting materials for the corresponding rapamycin dialdehydes, are disclosed in the above listed patents. The preparation of the corresponding oximes, hydrazones, and hydroxylamines of rapamycin dialdehyde can be accomplished using the methodology described in these patents, starting with rapamycin, followed by the ring opening reactions described herein.
Particularly preferred rapamycin dialdehydes include rapamycin dialdehyde, rapamycin dialdehyde 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid [see U.S. Pat. Nos. 5,362,718 and 6,277,539 for the preparation of rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid], and 42-O-(2-hydroxy)ethyl rapamycin dialdehyde [see U.S. Pat. No. 5,665,772 for the preparation of 42-O-(2-hydroxy)ethyl rapamycin].
When applicable, pharmaceutically acceptable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable aids when the rapamycin contains a suitable basic moiety. Salts may also be formed from organic and inorganic bases, such as alkali metal salts (for example, sodium, lithium, or potassium) alkaline earth metal salts, ammonium salts, alkylammonium salts containing 1-6 carbon atoms or dialkylammonium salts containing 1-6 carbon atoms in each alkyl group, and trialkylammonium salts containing 1-6 carbon atoms in each alkyl group, when the rapamycin contains a suitable acidic moiety.
As used in accordance with this invention, the term xe2x80x9cproviding,xe2x80x9d with respect to providing a compound or substance covered by this invention, means either directly administering such a compound or substance, or administering a prodrug, derivative, or analog which will form the equivalent amount of the compound or substance within the body.
The compounds of this invention can be made from a rapamycin using commercially available starting materials or from starting materials that can be prepared according to literature procedures. The desired rapamycin dialdehyde can be prepared by the treatment of the rapamycin with an oxidizing agent such as OsO4/sodium periodate or ozone by monitoring the progress of the reaction, until the desired product has formed. In addition to the production of the rapamycin dialdehyde, corresponding rapamycin 29-enols are also produced during the ozonolysis oxidation. The structure of rapamycin 29-enol is provided below.
Additionally, during the ozonolysis of the rapamycin, (2E,4S,6R)-6-[(5S,6R)-5-hydroxy-6-methoxy-4-methyl-2,3,7-trioxabicyclo[2.2.1]hept-1-yl]-4-methylhept-2-enal, having the structure shown below was produced (Example 3).
The neuroregeneration activity for the compounds of this invention was confirmed in a standard pharmacological test procedure by evaluating rapamycin dialdehyde (Example 1) and rapamycin 29-enol (Example 2), as representative compounds of this invention, against SH-SY5Y cells in vitro [Gold et al., Exp Neurol 147: 269-278, 1997]. Briefly, SH-SY5Y cells were placed in 6-well plate treated with aphidicolin for 5 days followed by the test compounds using 6-well plates. For controls, wells were untreated, or treated with nerve growth factor (NGF) alone. Test wells were treated with NGF plus Example 1 and Example 2, or rapamycin. Cells were photographed at 168 hours. Analysis of neuritic lengths was performed on photographic prints using a Houston Instrument HI-PAD digitizing tablet connected to an IBM XT computer with appropriate software (Bioquant IV, RandM Biometrics, Nashville, Tenn.). Mean values for axonal areas were compared using by ANOVA (STATVIEW, Abacus Concepts, Inc., Berkeley, Calif.). The following table summarizes the results that were obtained.
The results obtained in the standard pharmacological test procedure demonstrated that the compounds of this invention are useful as neurotrophic agents, and are particularly useful in promoting promote neuronal regeneration and functional recovery and to stimulate neurite outgrowth and thereby to treat various neuropathological states, including damage to peripheral nerves and the central nervous system caused by physical injury (e.g., spinal cord injury and trauma, sciatic or facial nerve lesion or injury), disease (e.g., diabetic neuropathy), cancer chemotherapy (e.g., by vinca alkaloids and doxorubicin), brain damage associated with stroke and ischemia associated with stroke, and neurological disorders including, but not limited to, various peripheral neuropathic and neurological disorders related to neurodegeneration including, but not limited to: trigeminal neuralgia, glossopharyngeal neuralgia, Bell""s palsy, myasthenia gravis, muscular dystrophy, amyotrophic lateral sclerosis, progressive muscular atrophy, progressive bulbar inherited muscular atrophy, herniated, ruptured or prolapsed vertebral disk syndromes, cervical spondylosis, plexus disorders, thoracic outlet destruction syndromes, peripheral neuropathies such as those caused by lead, acrylamides, gamma-diketones (glue-sniffer""s neuropathy), carbon disulfide, dapsone, ticks, porphyria, Gullain-Barre syndrome, dimentia, Alzheimer""s disease, Parkinson""s disease, and Huntington""s chorea.
Antineoplastic activity for the compounds of this invention was confirmed by evaluating the antineoplastic activity of representative compounds of this invention (Examples 1-5) against six tumor cell lines in vitro. Briefly, tumor cells from six cell lines were placed in wells of a 96 well microtiter plate. The following tumor cell lines were used: 3T3 (ovarian), 3T3/H2N (ovarianxe2x80x94resistant to cis-platin), A431 (vulva epidermoid origin), SW620 (colon), SKBR3 (breast), and MDA-435 (breast). The tumors cells were grown in the presence of serial dilutions of the compound to be evaluated for 48 hours, and cell growth determined using a colorimetric procedure (sulforhrodamine B). The inhibition of growth was calculated compared to the number of cells at the time of test compound addition. Results are expressed as an IC50 (xcexcg/ml); and are provided in Table 2.
The results of this standard pharmacological test procedure demonstrate that the compounds of this invention are useful as antineoplastic agents. In particular, the compounds of this invention are useful against solid tumors, including sarcomas and carcinomas; and more particularly against astrocytomas, prostate cancer, breast cancer, colon cancer, small cell lung cancer, and ovarian cancer; and adult T-cell leukemia/lymphoma.
The compounds of this invention are also useful in the treatment or inhibition of hyperproliferative vascular diseases such as restenosis
When used for restenosis, it is preferred that the compounds of this invention are used to treat restenosis that occurs following an angioplasty procedure. When used for this treating restenosis following an angioplasty, the compounds of this invention can be administered prior to the procedure, during the procedure, subsequent to the procedure, or any combination of the above.
It is understood that the effective dosage of a rapamycin dialdehyde may vary depending upon the particular compound utilized, the mode of administration, the condition, and severity thereof, of the condition being treated, as well as the various physical factors related to the individual being treated. As used in accordance with invention, satisfactory results may be obtained when the rapamycin dialdehyde is administered in a daily oral dosage of from about projected daily dosages of active compound would be 0.1 xcexcg/kg-100 mg/kg, preferably between 0.001-25 mg/kg, and more preferably between 0.01-5 mg/kg. The projected daily dosages are expected to vary with route of administration.
When the rapamycin dialdehyde is used as part of a combination regimen, dosages of each of the components of the combination are administered during a desired treatment period. The components of the combination may administered at the same time; either as a unitary dosage form containing both components, or as separate dosage units; the components of the combination can also be administered at different times during a treatment period, or one may be administered as a pretreatment for the other.
Such doses may be administered in any manner useful in directing the active compounds herein to the recipient""s bloodstream, including orally, via implants, parenterally (including intravenous, intraperitoneal and subcutaneous injections), rectally, intranasally, vaginally, and transdermally. For the purposes of this disclosure, transdermal administrations are understood to include all administrations across the surface of the body and the inner linings of bodily passages including epithelial and mucosal tissues. Such administrations may be carried out using the present compounds, or pharmaceutically acceptable salts thereof, in lotions, creams, foams, patches, suspensions, solutions, and suppositories (rectal and vaginal).
Oral formulations containing the active compounds of this invention may comprise any conventionally used oral forms, including tablets, capsules, buccal forms, troches, lozenges and oral liquids, suspensions or solutions. Capsules may contain mixtures of the active compound(s) with inert fillers and/or diluents such as the pharmaceutically acceptable starches (e.g. corn, potato or tapioca starch), sugars, artificial sweetening agents, powdered celluloses, such as crystalline and microcrystalline celluloses, flours, gelatins, gums, etc. Useful tablet formulations may be made by conventional compression, wet granulation or dry granulation methods and utilize pharmaceutically acceptable diluents, binding agents, lubricants, disintegrants, surface modifying agents (including surfactants), suspending or stabilizing agents, including, but not limited to, magnesium stearate, stearic acid, talc, sodium lauryl sulfate, microcrystalline cellulose, carboxymethylcellulose calcium, polyvinylpyrrolidone, gelatin, alginic acid, acacia gum, xanthan gum, sodium citrate, complex silicates, calcium carbonate, glycine, dextrin, sucrose, sorbitol, dicalcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, talc, dry starches and powdered sugar. Preferred surface modifying agents include nonionic and anionic surface modifying agents. Representative examples of surface modifying agents include, but are not limited to, poloxamer 188, benzalkonium chloride, calcium stearate, cetostearl alcohol, cetomacrogol emulsifying wax, sorbitan esters, colloidol silicon dioxide, phosphates, sodium dodecylsulfate, magnesium aluminum silicate, and triethanolamine. It is more preferred that poloxamer 188 is used as the surface modifying agent. Oral formulations herein may utilize standard delay or time release formulations to alter the absorption of the active compound(s). Preferred oral formulations of rapamycin is disclosed in U.S. Pat. Nos. 5,559,121; 5,536,729; 5,989,591; and 5,985,325, which are hereby incorporated by reference.
In some cases it may be desirable to administer the compounds directly to the airways in the form of an aerosol.
The compounds of this invention may also be administered parenterally or intraperitoneally. Solutions or suspensions of these active compounds as a free base or pharmacologically acceptable salt can be prepared in water suitably mixed with a surfactant such as hydroxy-propylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols and mixtures thereof in oils. Under ordinary conditions of storage and use, these preparation contain a preservative to prevent the growth of microorganisms.
The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils. Preferred parenteral formulations for administering rapamycin are disclosed in U.S. Pat. Nos. 5,530,006; 5,516,770; and 5,616,588, which are hereby incorporated by reference.
Suppository formulations may be made from traditional materials, including cocoa butter, with or without the addition of waxes to alter the suppository""s melting point, and glycerin. Water soluble suppository bases, such as polyethylene glycols of various molecular weights, may also be used.
When the rapamycin dialdehyde is used to treat or inhibit a hyperproliferative vascular disorder, such as restenosis, it is preferable that the rapamycin dialdehyde is provided via a vascular stent or shunt which has been coated or impregnated with the rapamycin dialdehyde.
The following provides procedures for the preparation of representative compounds of this invention.


A method and system for generating a hologram include a computer (104) connected to a printer (108). A mathematical description (102) of an object, including for example the physical dimensions of the object, is provided to the computer (104). The computer (104) computes a holographic interference pattern based on the mathematical description (102) of the object, and than transmits the computed holographic interference pattern data (106) to the printer (108). The printer (108) prints or otherwise fixes the holographic interference pattern to a print medium (107) to produce a holograph (110). A holographic (three-dimensional) image (114) of the object can then be produced by directing a light beam (118) from a light source (112) onto a surface of the hologram (110), so that the light will interfere with the pattern to generate the holographic image (114).

1. Field of the Invention
The invention relates to the field of holography.
2. Background Information
Holograms are typically created by directing laser light toward a three-dimensional physical object. More particularly, light from a visible spectrum laser is split into two beams, a first of which is directed onto a photosensitive medium, and the second of which is directed toward the object. The photosensitive medium is placed near the object, so that light from the second beam that is reflected by the object will strike the medium. The direct light from the first beam and the reflected light from the second beam combine and interfere to produce an interference pattern on the photosensitive medium.
After the exposure process is complete, the photosensitive medium is developed to fix the interference pattern on and/or in the photosensitive medium. The developed medium can then be used to generate a three dimensional image of the object by directing a beam of coherent light onto the medium so that the interference pattern fixed in the medium can alter the beam to generate the image. This beam is preferably a) coherent and b) has a wavelength that is the same or similar to the wavelength of the coherent light used to initially generate the interference pattern. The interference pattern may have lines that are separated only by several wavelengths of the light used to generate the interference pattern.
The resolution and technical limitations of available photosensitive media, can result in a relatively long exposure time to capture the holographic interference pattern. The average exposure necessary to capture a holographic interference pattern with a photosensitive medium can range, for example, from about a second to about a minute. This long exposure time, coupled with the fine resolution of the interference pattern means that the process of capturing a holographic interference pattern with a photosensitive medium is sensitive to vibration. Thus, intricate and massive arrangements are often used to capture a holographic interference pattern with a high degree of quality. For example, the object to be holographed, a laser and beam splitting mechanism, and the photosensitive medium are often placed together on an isolation table such as a granite slab weighing hundreds or thousands of pounds.
In sum, the process of a) generating a holographic interference pattern using a first portion of coherent light that is reflected from an object and a second portion of the coherent light provided as an off-axis beam, and then b) accurately capturing and then fixing the pattern in a photosensitive medium suitable for later generating a holographic image of an object upon exposure to an appropriate light source, is often cumbersome, resource-intensive and expensive.
However, the three dimensional nature of holographic images can be very useful in a variety of contexts. For example, in a scientific, engineering or business presentation a holographic three dimensional model can be advantageously used to quickly and clearly convey information and understanding to an audience.
Accordingly, a need exists for a method and apparatus that can easily, accurately and inexpensively generate and capture holographic interference patterns and generate corresponding holographic images.
In accordance with exemplary embodiments of the invention, a method and apparatus are provided for accurately and inexpensively generating a holographic interference pattern based on a mathematical description of an object, fixing the interference pattern in a medium, such that a three dimensional holographic image of the object can be generated using the medium. In accordance with an exemplary embodiment of the invention, a method for storing a holographic interference pattern includes the steps of a) computing the holographic interference pattern based on a mathematical description of an object, and b) forming a medium including the interference pattern. The interference pattern modifies incident light so that the modified light includes a holographic image of the object.
For example, the holographic image can be generated by directing at least one beam of light onto a surface of the medium to modify the beam of light with the interference pattern, the modified beam comprising the holographic image. The incident light or at least one beam of light directed onto the surface of the medium can be coherent light. The step of computing can use quantum electrodynamics. In accordance with an exemplary embodiment of the invention, the computed interference pattern can be partitioned and each partition can be represented as a weighted sum of basis interference patterns. A suitable means such as a digital computer or any other appropriate processing device can be provided for computing the interference pattern based on the mathematical description of the object. A suitable means for forming the medium including the interference pattern is provided, and can include a printer having a sufficiently high resolution to print the computed interference pattern onto a suitable medium, for example a transparent medium. A means for generating the image using the medium including the interference pattern is provided, and can include at least one light source, for example a laser device emitting coherent light.

Method and apparatus for generating a hologram

Hewlett-Packard Development Company, L.P.


A multiple effect diffusion distillation system includes a plurality of parallel plates for continuous recovery of heat having opposed evaporation and condensation faces for alternately evaporating and condensing phases of a liquid fed on to the upper end of the plates in a thin film for gravity flow along the evaporator face of the plates with vapor condensing on the condensation faces and with means for collecting and recovering the condensed product from the system. Alternate embodiments including a solar heat input system and others include multiple modular systems.

The present invention relates to distillation systems and pertains particularly to multiple effect distillation systems.
The use of a distillation process, that is evaporation and condensation of the vapors, for the separation of binary phase and multiple phase liquids have been known for some time. Most commercial distillation systems utilize a simple boiler for bringing the liquid to its boiling point to vaporize the liquid and draw off the vapor into a condenser where it is condensed and recovered. Such systems are satisfactory for many applications where the cost of energy is not a factor. Such systems, however, require a considerable amount of energy in order to properly function.
Other commonly known distillation systems are discussed and described in the background of U.S. Pat. No. 3,788,954 issued Jan. 20, 1974 to Mr. C. M. Cantrell, co-inventor hereof. The aforementioned patent covers a novel additional approach to the separation of liquid phases. That patent discloses and is directed to an interphase mass transfer process from laminer flowing thin films.
Many areas of the world and even areas of the United States have inadequate supplies of fresh or potable water. Although salt water is available in many of these areas, economical and effective means of converting it to fresh water is not available. Distillation is one method available for recovering fresh water from salt water. The prior art distillation systems are not sufficiently effective and economical to solve this problem.
We have conceived and developed a multiple effect diffusion distillation process that is easily adaptable to many different sources of energy. The broad aspects of a solar multiple effect distillation system were disclosed in my article dated June, 1976, appearing in volume 6, No. 6 of Solar Energy Digest, published by CWO-4, William B. Edmonson, San Diego, California. Since that time we have developed the system as well as numerous improvements which enhance the efficiency of that system as well as other applications of the multiple effect distillation system.
The multiple effect distillation system of the present invention has been found to be highly energy efficient as well as compact and simple to manufacture and operate.

Multiple effect thin film distillation system


The present invention refers to a method for treating wood in order to prevent or control the occurrence of stains such as sapwood stains, the method comprising a step of heating green wood in a moisture-saturated environment until the wood core temperature is in a range of about 60 degrees C. to 95 degrees C., followed by a step of gradually cooling the wood, wherein the wood is maintained in an environment with moisture contents ranging from 95% to 100% during said cooling step.

The present invention refers to a method for treating wood in order to prevent or to control the occurrence of stains thereon. The invention is particularly directed to a treatment for preventing the occurrence of sapwood stains.
After wood has been cut from the trees it remains exposed to a process of decomposition and deterioration. For the industry, and especially for the furniture and civil construction industries, one of the most relevant and undesirable consequences of wood deterioration is the occurrence of stains and cracks that, together with the presence of knots and other visible defects, impair its occurrence and, as a result, makes it difficult to use that wood for those specific purposes.
There are many factors responsible for wood deterioration, namely: physical, chemical and biological factors. Among the biological factors one can mention the bacteria or fungi challenges that may be prevented or treated by impregnating the wood with biocides. But there is also the biological deterioration caused by non-microbial factors such as enzymatic reactions and that also leads to the occurrence of stains on wood.
For example, wood that comes from many species of trees develops ash-colored stains, caused by enzymatic reactions and that are called xe2x80x9csapwood stainsxe2x80x9d. Although the origin of such stains is not accurately understood, it is known that as the cells of the wood parenchyma die, they produce enzymes that oxidizes and generally become ash-colored. The stain intensity and extension vary according to each different specie of wood (tree). This kind of stain is described in the technical literature with respect to species such as red oak, sugar hackberry (Celtis laevigata), flowering ash (Fraxinus spp.), yellow-poplar (Liriodentron tuipifera L.), among others. In the case of the eucalyptus species, for example, by effecting a cross section on the wood it is possible to observe the occurrence of a sapwood stain which develops from the transition region between the core and the sapwood (also called xe2x80x9calburnumxe2x80x9d) until it spreads all over the sapwood portion. Usually, after eucalyptus wood boards have been cut and planed, they present ash-colored stains which makes it very difficult and inappropriate to use them for end products that are supposed to be later used with an apparent finishing.
Various methods have been developed to prevent the occurrence of enzymatic origin stains on wood. For example, methods according to which wood is subjected to thermal treatment are already known, which methods may be carried out by means of vapors (steaming), microwaves or by dipping the wood into hot water. In this regard, article xe2x80x9cOxidizing Enzymes and their Relation to Sap Stain in Lumberxe2x80x9d, published in the xe2x80x9cBotanical Gazette of 1910, already described a preventive treatment that comprises dipping wood into boiling water (100xc2x0 C.) for a few minutes. According to that document, the immersion in water prevents the occurrence of stains, However, in order to ensure that no stain would occur the thus treated wood should be cooled under covering so as to avoid its exposition to light.
The use of chemical compounds for treating wood in an attempt to avoid the occurrence of unwanted stains is also known from prior art. Chemical compounds such as sodium methabisulfite, bromide, ammonia, among others, are described as being suitable for killing the cells of the parenchyma in a controlled way or for preventing the oxidation process, thus avoiding the formation of stains. An example of a process using chemical compounds for this purpose is described in U.S. Pat. No. 5,480,679.
Other methods described for preventing stains on logs comprise the application of mechanical force, like the method described in U.S. Pat. No. 5,858,484, according to which a mechanical force such as compression and vibration is to the wood for some time and with an intensity sufficient to produce or eliminate the stain.
However, all methods already known from the prior art present undesirable side effects such as, for example, the formation of dark stripes as the ones that result from the sodium methabisulfite treatment, or the occurrence of surface cracks on wood that is treated by steaming or by merely dipping it into hot water, which equally disqualifies that wood for determined and specific end uses, apart from involving considerable high costs.
In addition, methods that comprise treating wood with chemical compounds have the further disadvantage that many of those compounds are toxic or, at least, generate very bad smell, which causes a serious discomfort to the technicians involved and to the persons who work close to the wood treatment station.
Therefore, the objective of the present invention is to provide an efficient and inexpensive method for the treatment of wood with a view to preventing or controlling the occurrence of stains thereon and that will integrally preserve its structure, without causing cracks or any other defects on the wood.
The present invention refers to a method for treating wood to prevent or control the occurrence of stains, which comprises a step of heating the green wood in a moisture-saturated environment until the temperature of the wood core is in a range of about 60xc2x0 C.-95xc2x0 C., followed by a step of gradually cooling the wood. During the cooling step, the wood is maintained in an environment having a moisture content in the range from 95% to 100%.
The inventors have found that it is possible to avoid or decrease considerably the occurrence of stains on wood, mainly enzyme-originated stains (sapwood stains), by a thermal treatment comprising the steps of controlled heating and cooling wood in an atmosphere with specific moisture contents, which provides the conditions required to prevent the formation of cracks and other undesirable side-effects on the wood.
According to the method of the invention, green wood, which may be cut into logs or boards, is subjected to a heating step in a moisture-saturated atmosphere. The saturation during the heating should be total, that is to say, the moisture contents in the environment in which the wood is heated should be of 100%. According a preferred embodiment of the invention, the heating step is carried out by dipping the wood into a hat water bath, which ensures the required moisture environment.
The high heating temperature causes the death of the wood parenchyma cells, thus preventing the activity of these cells and the consequent process of enzymatic oxidation that would form the stains, while the saturation of the environment prevents the formation of surface cracks.
The heating temperature should be sufficient for the wood core to reach a range of about 60 to 95xc2x0 C., preferably about 85xc2x0 C. For this reason, and as it can be promptly verified by any person skilled in the art, the temperature in the heating environment as well as the necessary time for the wood to be maintained therein will depend upon various factors, such as the thickness of the logs or boards to be treated, their density, among others. The essential aspect, however, is that the temperature and the time are established in such a way that the heating of the core region can reach the above-mentioned temperature range.
After the heating step, wood is then left to cool in an environment that preserves its moisture contents within a range of from 95 to 100%. It is necessary that the cooling step is carried out in this way in order to achieve the desired results, so that the moisture on the wood surface will not be lost after the heating; otherwise, the possibility of occurrence of surface cracks increases due to the internal and superficial moisture gradient that is generated. It must be observed that that occurrence of cracks may be potentialized in function of numberless other factors such as the predisposition of the material to form cracks caused by growth stress, inadequate cutting of the logs into planks, among others. However, even in these cases the formation of cracks is substantially reduced by the process of the invention.
Preferably, the cooling step is carried out by covering the heated material with a moisture-impermeable material. This is a simple way of ensuring that the cooling takes place by maintaining the required level of moisture. However, the cooling may be carried out in any way that guarantees the maintenance of the moisture within the desired range, that is to say, that prevents the rapid loss of moisture from the wood surface to the environment. Examples of means and procedures suitable to be used in the cooling step include, for instance, cooling tunnels or dipping wood into water. In a preferred way, the treated wood is only exposed to the ambient air after it has been cooled until the wood core temperature reaches a value of about 45xc2x0 C. or is within a range of from 10xc2x0 C. to 20xc2x0 C. above room temperature, which will depend upon the treated species and the place (environment), in order to prevent a thermal shock and its consequences.
The presently claimed method also presents additional advantages, since it can be used in association with other methods in which preservatives such as borates are employed, besides alleviating the growth stress in the treated boards or logs.
The method of the present invention is suitable for preventing or controlling the occurrence of stains of enzymatic origin on various species of wood, such as species of the genus Eucalyptus, the use of which has recently been increasing on the market of furniture production as well as for other applications where an xe2x80x9capparentxe2x80x9d (visual) form is required, in which case the prevention of wood discoloration and deterioration is of extreme relevance.

Method for preventing or controlling the occurrence of stains on wood


An apparatus and method for supplying multi-color powder paint material to an applicator in which at least one canister is used. This invention can be utilized with multiple or with a single color of powder paint material. The preferred system includes two canisters that alternate in supplying powder to the applicator. While one canister supplies powder to the applicator, the other canister is purged of the previous material and filled with the next material to be sprayed. The canister has an interior sized to store a predetermined quantity of powder material. During operation, a powder transfer pump and a color changer transfer powder material from a storage container/hopper to the canister interior. A venturi pump then supplies the applicator with powder. After the object is painted, purge air is opened and the canister is purged of the previous material. The canister is then ready to start another cycle.

The present invention relates in general to powder paint transfer and distribution systems for use with powder coating applicators and, in particular, to a canister powder paint delivery apparatus and method for applying both multi-color powder (i.e. color key and or color specific) and single color powder.
In prior art systems, the powder paint is unloaded from a tote bulk storage system by a vacuum transport directly to a receiver. Alternatively, the powder paint is gravity fed from a bag bulk storage system into a vacuum stream. The unloaded powder in the receiver is then conditioned utilizing a sieve and gravity fed to a primary fluidized hopper. The powder paint is transferred from the primary hopper to a secondary fluidized hopper located approximately 25 feet from the point of application. The powder paint is fed from the secondary hopper or hoppers to the applicators. Disadvantageously, one complete distribution system that includes the bulk storage, sieve, primary hopper and secondary hopper is needed for each color of powder to be sprayed. Typically, one secondary hopper can supply six applicators, also a third level of hoppers is added for cut-ins and supplemental robotic application. Typically, there is one hopper per color of powder connected to each robot. This system requires that each color of powder have a series of hoppers, so that each color added to the system increases the number of primary, secondary, and robot hoppers required in the system. A venturi pumping system is used to transfer the powder paint material between the hoppers and the applicator. For example, a three color color-keyed and ten color color-specific system requires ten to thirteen primary hoppers, fifty to sixty secondary and/or robot hoppers, over one hundred fifty venturi pumps, and over twenty color changers.
It is desirable, therefore, to provide a simple, inexpensive, and efficient apparatus for supplying multi-color powder paint material to an applicator in a powder paint delivery system.

Canister powder paint delivery apparatus and method


This invention is directed to a surfactant comprising a heterocyclic group that results in superior cleaning in a dry cleaning system. The surfactant can have one or more heteroatom and can result in reverse micelle formation in a densified gas like densified carbon dioxide.

This invention is directed to a surfactant comprising a heterocyclic group. More particularly, the invention is directed to a surfactant comprising a heterocyclic group that results in superior cleaning properties in a dry cleaning system.
In many cleaning applications, it is desirable to remove contaminants (e.g., stains) from substrates, like metal, ceramic, polymeric, composite, glass and textile comprising substrates. Particularly, it is highly desirable to remove contaminants from clothing whereby such contaminants include dirt, salts, food stains, oils, greases and the like.
Typically, dry-cleaning systems use organic solvents, like chlorofluorocarbons, perchloroethylene and branched hydrocarbons to remove contaminants from substrates. In response to environmental concerns, other dry-cleaning systems have been developed that use inorganic solvents, such as densified carbon dioxide, to remove contaminants from substrates. The systems that use carbon dioxide to remove contaminants from substrates generally employ a surfactant and a polar co-solvent so that a reverse micelle may be formed to trap the contaminant targeted for removal.
In view of the environmental concerns associated with dry cleaning in, for example, halogenated hydrocarbons, many cleaning establishments have expressed their interests in cleaning with continuous phase solvents that comprise densified gases such as densified carbon dioxide as well as a biodegradable functionalized hydrocarbon or a silicon comprising surfactant. Unfortunately, however, cleaning with such solvents is not made easy because only very few surfactants are compatible with such continuous phases.
It is of increasing interest to develop surfactants that enhance cleaning in a system that uses a densified gas, functionalized biodegradable hydrocarbon and/or a silicon comprising solvent. This invention, therefore, is directed to a surfactant comprising a heterocyclic group that unexpectedly results in superior cleaning properties in a dry cleaning system that utilizes a densified gas, a functionalized biodegradable hydrocarbon and/or silicon comprising solvent.
Efforts have been disclosed for dry cleaning with carbon dioxide. In U.S. Pat. No. 5,676,705, a superior dry cleaning method which employs densified carbon dioxide is described.
Other efforts have been disclosed for dry cleaning with carbon dioxide. In U.S. Pat. No. 5,683,473, a superior method for dry cleaning fabrics with a surfactant having a polysiloxane, branched polyalkylene oxide or halocarbon group is described.
Still further, U.S. Pat. No. 5,683,977 discloses a superior dry cleaning system with carbon dioxide and a surfactant adjunct.
Finally, in U.S. Pat. No. 5,866,005, a cleaning process using carbon dioxide as a solvent along with molecularly engineered surfactants is described.
In a first embodiment, the present invention is directed to a dry cleaning system comprising a surfactant having the formula:
A-Z
wherein A is a portion of the surfactant that is soluble in carbon dioxide and Z is a portion of the surfactant that is not soluble in carbon dioxide and Z comprises a heterocyclic group, with the provisos that:
(i) when Z is pyrrolidone, nitrogen is not substituted with a hydrocarbon having less than five carbon atoms;
(ii) when Z is a polymeric vinyl pyrrolidone, the dry cleaning system is a system for removing soil from fabrics;
(iii) when A is a polysiloxane, Z is not a beta carboxylic acid substituted pyrrolidone having the polysiloxane joined to nitrogen with a bridging radical; and
(iv) when A is not a hydrocarbon, Z is not a carbohydrate.
In a second embodiment, the present invention is directed to a method for dry cleaning using the dry cleaning system of the first embodiment.
There generally is no limitation with respect to the surfactant used in this invention as long as the surfactant will enhance cleaning in a system which utilizes a continuous phase solvent comprising a densified gas, biodegradable functionalized hydrocarbon or a silicon comprising solvent, and the surfactant meets the criteria set forth in the above-described provisos (i)-(iv).
Often, the surfactants which may be used in this invention are selected from the group consisting of
wherein each R and T are independently a hydrogen, C5 to C18 hydrocarbon, polysiloxane, CO2 soluble polyalkylene oxide or halocarbon, with the proviso that at least T or one R group is not hydrogen, L is C(R2) or y-(T)t, x is an integer from about 1 to about 6, each y is independently N, P, S, B or O and t is 0 or 1 with the proviso that t is 0 when y is oxygen.
In a preferred embodiment the hydrocarbon is a C6 to C12 hydrocarbon, the polysiloxane is polydimethysiloxane with or without polypropylene oxide substituents and having a weight average molecular weight of about 200 to about 200,000, the polyalkylene oxide is polypropylene oxide having a weight average molecular weight of about 100 to about 100,000, and the halocarbon is a C2 to C8 fluoroalkylene or fluoroalkenylene, x is an integer from about 2 to about 4 and the heteroatom is N. The preferred polysiloxanes and halocarbons are derived from those described in U.S. Pat. Nos. 5,676,705, 5,683,473 and 5,683,977, the disclosures of which are incorporated herein by reference. The preferred polysiloxanes are often bridged to the heterocyclic group with a C1 to C20 hydrocarbon bridging radical, and preferably, a C3 hydrocarbon bridging radical.
In a most preferred embodiment, structure I represents the surfactant comprising a heterocyclic group and each R is hydrogen, y is N, T is a C8 or C12 hydrocarbon, L is C(R2), x is 2 and t is 1. When T is a C8 hydrocarbon, such a surfactant is sold under the name Surfadone LP-100 and when T is a C12 hydrocarbon, such a surfactant is sold under the name Surfadone LP-300, both of which are made commercially available by International Specialty Products. Still another most preferred embodiment results when at least one R is a C5 to C18 group, L is oxygen, y is oxygen and x is 2.
The surfactant comprising the heterocyclic group which may be used in this invention can be prepared via numerous well known processes which include the condensation of butyrolactone with methylamine. Such reactions are disclosed in The Kirk-Othmer Encyclopedia of Chemical Technology, Volume 20, 4th Edition, pages 697-720 (1996), the disclosure of which is incorporated herein by reference.
Other surfactants comprising heterocyclic groups which may be used in this invention (as defined by the formulas above) include those made and described in Introduction to Organic chemistry, Second Edition, Streitwieser, Jr. et al., Chapter 32 (1981), the disclosure of which is incorporated herein by reference.
Still other surfactants that may be used in this invention (as defined by the formulas above) include those prepared by a conventional hydrosilation reaction wherein at least one reactant comprises a heterocyclic group.
If desired, the surfactants which can be employed in this invention may be purchased from suppliers such as BASF, Arco and, again, International Specialty Products.
There generally is no limitation with respect to the continuous phase solvent (i.e., fluid) which may be employed with the surfactants comprising a heterocyclic group of this invention other than that the solvent is a densified gas (e.g., fluid which is a gas at standard temperature and pressure), a biodegradable hydrocarbon or a silicon comprising solvent, and capable of being a continuous phase in a dry cleaning application. Illustrative examples of the types of solvents which may be employed in this invention include a C2-C4 substituted or unsubstituted alkane, carbon dioxide, silicone oil, and an azeotropic solvent.
Regarding the solvent which is a densified gas, such a solvent may be, within the dry cleaning composition or process, a gas, liquid or supercritical fluid depending upon how densified the solvent is (how much pressure is applied at a given temperature) in the domestic or commercial cleaning application the solvent is used in. Propane and carbon dioxide tend to be the preferred solvents when the solvent selected is one which is a densified gas. Carbon dioxide, however, is especially preferred.
As to the silicon comprising solvent which may be used in this invention, such a solvent is typically a commercially available cyclic-siloxane based solvent made available from GreenEarth Cleaning, LLC. Such a solvent is generally one which has a flash point over about 65xc2x0 C., with octamethyl-cyclotetrasiloxane and decamethyl-cyclopentasiloxane being most preferred. A more detailed description of such conventional siloxane comprising solvents may be found in U.S. Pat. No. 5,942,007, the disclosure of which is incorporated herein by reference.
Especially preferred silicon comprising solvents are those having the formula:
wherein each R is independently a substituted or unsubstituted linear, branched or cyclic C1-10 alkyl, C1-10 alkoxy, substituted or unsubstituted aryl, aryloxy, trihaloalkyl, cyanoalkyl or vinyl group, and R1 is a hydrogen or a siloxyl group having the formula:
Si (R2)3xe2x80x83xe2x80x83V
and each R2 is independently a linear, branched or cyclic C1-10 substituted or unsubstituted alkyl, C1-10 alkoxy, substituted or unsubstituted aryl, trihaloalkyl, cyanoalkyl, vinyl group, amino, amido, ureido or oximo group, and R1* is an unsubstituted or substituted linear, branched or cyclic C1-10 alkyl or hydroxy, or OSi(R2)3 whereby R2 is as previously defined, and e is an integer from about 0 to about 20.
The most preferred linear siloxane solvent is one wherein each R is methyl, R1 is Si (R2)3, R2 is methyl and R1* is methyl. Preferably, e is an integer from about 0 to about 10, and most preferably, an integer from about 2 to about 5.
Such solvents are made commercially available by General Electric, and Dow Corning under the name Dow Corning 200(R) fluid. A description of the solvents may be found in U.S. Pat. Nos. 3,931,047 and 5,410,007, the disclosures of which are incorporated herein by reference.
The biodegradable functionalized hydrocarbon that may be used in this invention includes those generally classified as an azeotropic solvent. Such an azeotropic solvent often comprises alkylene glycol alkyl ethers, like propylene glycol tertiary-butyl ether, and is described in U.S. Pat. No. 5,888,250, the disclosure of which is incorporated herein by reference. Moreover, as used herein, biodegradable functionalized hydrocarbon is defined to mean a biodegradable hydrocarbon comprising at least one member selected from the group consisting of an aldehyde, ketone, alcohol, alkoxy, ester, ether, amine, amide and sulfur comprising group.
When dry cleaning, for example, fabrics, like clothing or garments, with a solvent that is a densified gas (and the surfactants of this invention), the machine which is employed for cleaning is well known in the art. Such a machine typically comprises a gas supply, cleaning tank and condenser. The machine may further comprise a means for agitation. The means for agitation may be, for example, a mechanical device like a mechanical tumbler, or a gas-jet agitator. The art recognized machines which may be used in this invention (e.g., when a densified gas is used) may be found in U.S. Pat. Nos. 6,012,307, 5,943,721, 5,925,192, 5,904,737, 5,412,958, 5,267,455 and 4,012,194, the disclosures of which are incorporated herein by reference.
When dry cleaning for example, fabrics, like clothing or garments, with the biodegradable functionalized hydrocarbons or silicon comprising solvents and the surfactants described in this invention, the type of machine that may be used for the dry cleaning process is the same or substantially the same as the commonly used dry cleaning machines used for dry cleaning with perchloroethylene. Such machines typically comprise a solvent tank or feed, a cleaning tank, distillation tanks, a filter and solvent exit. These commonly used machines are described, for example, in U.S. Pat. No. 4,712,392, the disclosure of which is incorporated herein by reference.
When the fabric is placed in the machine and the continuous phase solvent of choice is fed into the machine, the normal cleaning cycle is run (typically between ten (10) minutes and one (1) hour). Prior to or after the start of the cleaning cycle, the heterocyclic surfactant of this invention is introduced into the cleaning machine. Any of the surfactants represented by formulae I to III may be used, including any combination thereof. Often, the amount of surfactant employed is from about 0.001 to about 15.0%, and preferably, from about 0.01 to about 5.0%, and most preferably, from about 0.01 to about 3.0% by weight of surfactant, based on total weight of surfactant and continuous phase solvent, including all ranges subsumed therein.
In addition to continuous phase solvent and the surfactant described in this invention, it is especially preferred to add from about 0.01% to about 10.0%, and preferably, from about 0.03 to about 3.0%, and most preferably, from about 0.05 to about 0.3% by weight of a polar additive (e.g., C1-10 alcohol and preferably water) based on total weight of continuous phase solvent, surfactant and polar additive, including all ranges subsumed therein. The addition of polar additive to the continuous phase solvent and surfactant is often desired so that cleaning may be enhanced, for example, by the formation of reverse micelles.
When cleaning fabrics, for example, with the surfactants of this invention, the pressure and temperature of the dry cleaning system (e.g., the system comprising the fabric targeted for cleaning, the continuous phase solvent and the surfactant described in this invention) within the machine is limited only to the extent that the temperature and pressure allow for the fabric to be cleaned. The pressure is often from about 14.7 to about 10,000 psi, and preferably, from about 200 to about 5,000 psi, and most preferably, from about 250 to about 3,000 psi, including all ranges subsumed therein. The temperature is often from about xe2x88x9230.0 to about 100xc2x0 C., and preferably, from about xe2x88x925.0 to about 70.0xc2x0 C., and most preferably, from about 0.0 to about 45xc2x0 C., including all ranges subsumed therein.
It is also noted herein that optional additives may be employed when cleaning with the surfactants described in this invention. Such optional additives include an oxidizing agent, like hydrogen peroxide, and an organic bleach activator such as those represented by the formula:
wherein n is an integer from about 0 to about 20 and X is hydrogen or SO3M and M is hydrogen, an alkaline metal or an immodium cation. A more detailed description of such additives may be found in U.S. Pat. No. 5,431,843, the disclosure of which is incorporated herein by reference.
Other optional additives that may be employed to clean with the surfactants described in this invention include anti-static agents and deodorizing agents. Such anti-static agents typically include C8-C12 alcohol ethoxylates, C8-C12 alkaline glycols and glycol esters. The deodorizing agent, on the other hand, typically includes fragrances such as those described in U.S. Pat. No. 5,784,905, the disclosure of which is incorporated herein by reference.
Still other optional additives include viscosity modifiers like propylene glycol and sodium xylene sulphonate. As to the amount of optional additives used with the surfactants of the present invention, such an amount is limited only to the extent that the additive does not interfere with the cleaning process.

Heterocyclic dry-cleaning surfactant and method for using the same

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