An estimated forty percent of women experience sexual difficulties at some period during their life. Female sexual dysfunction includes complications with arousal, desire, orgasms and/or painful intercourse. Studies have shown that women only achieve an orgasm 25% of the time via sexual intercourse alone. In many cases the physiological factors can be attributed to decrease in blood flow to genital region, particularly to the clitoris.
Prescription and over-the counter medications, illicit drugs and alcohol abuse contribute to sexual dysfunction. There are separate lists of drugs or medications that cause disorder of desire, medications that cause disorder of arousal and medications that cause orgasmic dysfunction.
Estimates of the number of women who have sexual dysfunction range from 19 to 50% in “normal” outpatient populations and increase to 68 to 75% when sexual dysfunction or problems that are not dysfunctional in nature are included.
A decline in desire, arousal, and frequency of intercourse and an increase in dyspareunia or painful intercourse have also been associated with menopause.
However, there is also a large population of women who have sexual dissatisfaction that is not truly medically dysfunctional in nature or associated with menopause. This general population of women wishes to achieve sexual satisfaction or improve their sexual performance by achieving and/or enhancing the orgasm.
Products are currently on the market that claim to be invigorating lubricants or are intended to aid in stimulating the clitoris to increase the duration and intensity of climax. Most of these ingredients are claimed to be vasodilators that act to increase sensitivity. For example, niacin-containing products include Climatique, distributed by Climatique International, Inc., Ioxora, distributed by Ioxora Bio-Medical Co New York, N.Y. 10175, Emerita Response, Manufactured by Emerita®, Portland Oreg., OR 97205, and Vibrel® manufactured for GlycoBiosciences, Inc, Campbellville, Canada. These niacin-containing products, however, are aqueous compositions and when applied to the skin, result in irritation, itching and/or redness of the skin also known as a “flushing” response, which lasts for considerably long duration.
Accordingly, there remains a need for women, and men, who wish to achieve or enhance sexual satisfaction or improve their sexual performance by achieving and/or enhancing the orgasm in a manner that is free from side effects. Also, there is a need for a test that can qualitatively and quantitatively determine the actual blood flow on the area of human skin and can also monitor changes in this blood flow. The methods and compositions of the present invention answer this need.
It has been discovered that anhydrous compositions comprising a vasodilator result in an increase in blood flow but do not cause flushing or redness of the skin. Specifically, the vasodilatation caused by the compositions of this invention is controlled because the anhydrous base is responsible for penetration of the niacin and/or other effective vasodilators to the deeper layers of the tissue, which we theorize penetrates at least through the stratum corneum and preferably the epidermis. This results in a desired increase in blood flow without the undesired side effect of flushing.
Accordingly, the invention relates to an anhydrous composition comprising a vasodilator and an acceptable carrier wherein the vasodilator is present in an amount effective to increase the blood flow when the composition is applied to human tissue. The anhydrous compositions according to the invention preferably contain less than 20% water, more preferably less than about 5% water and most preferably, less than about 3% water.
In another embodiment, the invention relates to a method of attaining enhanced sexual response or sexual wellness of an individual comprising administering to the genital areas of the individual, an anhydrous composition comprising an effective amount of a vasodilator.
In yet another embodiment, the invention relates to a method for measuring the efficacy of a composition for improving sexual wellness comprising:
A more particular description of the invention, briefly summarized above may be had by reference to the embodiments thereof that are illustrated in the appended figures. It is to be so noted, however, that the appended figures illustrate only typical embodiments of the invention and, therefore, are not to be considered limiting of its scope, for the invention may admit to other equally effective embodiments.
It is believed that one skilled in the art can, based upon the description herein, utilize the present invention to its fullest extent. The following specific embodiments are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Any percentage (%) concentration of a component is weight by weight (w/w) unless otherwise indicated.
This invention relates to sexual enhancement compositions for use by both the male and the female. These sexual enhancement compositions work by increasing the blood flow to the sexual areas of both the male and female. Since the target area of these compositions is local, these compositions do not cause side effects from systemically-administered erectile dysfunction medications such as VIAGRA® or other medications that are similar in mechanism in the males and undesirable side effects of other active ingredients in the compositions used for FSD (Female Sexual Dysfunction), such as topically-administered testosterone or other hormone-containing medications that are topically or systemically administered. Such undesirable side effects include, for example, decrease in blood pressure, formation of blood clots, heart attacks and cancer.
The main objects of the sexual enhancement compositions of this invention are as follows:
These objects are accomplished through the administration of the anhydrous compositions of the invention comprising, consisting essentially of, and consisting of a vasodilator and an acceptable carrier. Suitable vasodilators include niacin derivatives such as nicotinic acid also called Niacin or Vitamin B3, nicotinates, such as, methyl nicotinate, benzyl nicotinate, nicotinamide, methyl niconate and niacinamide. We believe that other vasodilators, in particular, vasodilators capable of penetration to the deeper layers of the tissue at least through the stratum corneum and preferably the epidermis but do not cause flushing would be useful to achieve the desired results in the compositions and methods of this invention. Vasodilators may be categorized as being endogenous (i.e., normally produced within the body) or exogenous (i.e., normally produced outside of the body). Endogenous vasodilators preferably include nitric oxide, histamine, prostaglandin D2, adenosine, L-arginine, bradykinin as well as niacin and the like. Exogenous vasodilators include nitric oxide inducers and PDE5 inhibitors. Nitric oxide inducers include glyceryl nitrate (commonly known as nitroglycerin), isosorbide mononitrate, isosorbide dinitrate, pentaerythrotol tetranitrate and sodium nitroprusside. PDE5 Inhibitors include sildenafil, tadalafil, vardenafil, theobromine and papaverine and the like.
In one embodiment, a preferred vasodilator is one that normally causes flushing in aqueous compositions but does not cause flushing in the compositions according to the invention. In yet another embodiment, the compositions according to the invention do not contain a niacin derivative or contain, for example less than 0.1%, of a niacin derivative.
In one embodiment nicotinic acid or niacin is the preferred derivative as methyl nicotinate has been found to have a strong undesirable odor. Generally, the niacin derivative is present in the anhydrous composition in an amount effective to increase the blood flow to human tissue. In one embodiment the vasodilator is present in an amount ranging from about 0.1 to about 0.5% by weight, for example from about 0.1 to about 0.2% by weight. Depending upon their potency, other exogenous and endogenous vasodilator ingredients may be present in the compositions of this invention in smaller ranges, i.e., preferably from about 0.05 to about 0.15% by weight, more preferably from about 0.08 to about 0.12% by weight and most preferably, about 0.1% by weight.
The anhydrous compositions of the invention comprise an acceptable carrier. By “acceptable carrier” it is meant any non-aqueous carrier that will not interfere with the object of this invention. Suitable acceptable carriers include polyhydric alcohols as described in copending U.S. patent application Ser. No. 11/403,592, filed Apr. 13, 2006, the disclosure of which is hereby incorporated by reference. Examples include polyethylene glycol (hereinafter, “PEG”). Polyethylene glycol ethers may also be used, including PEG ethers of propylene glycol, propylene glycol stearate, propylene glycol oleate and propylene glycol cocoate and the like. Specific examples of such PEG ethers include PEG-25 propylene glycol stearate, PEG-55 propylene glycol oleate and the like. Preferably, at least one of the polyhydric alcohols of the compositions of this invention is a polyalkylene glycol or others selected from the following group: glycerine, propylene glycol, butylene glycol, hexylene glycol or polyethylene glycol of various molecular weight and the like and/or combination thereof. More preferably, the compositions of this invention contain a polyethylene glycol; most preferably, the polyethylene glycol may be selected from the following group: polyethylene glycol 400 or polyethylene glycol 300. Polypropylene glycol of various molecular weights may also be used. PEGylated compounds such as peptide or protein derivatives obtained through PEGylation reactions may also be used. In addition, block copolymers of PEG's may be used, such as (ethylene glycol)-block-poly(propylene glycol)-block-(polyethylene glycol), poly(ethylene glycol-ran-propylene glycol) and the like. The compositions of this invention should contain polyhydric alcohols in an amount from about 80% to about 98% by weight of the composition.
Preferably, the compositions of this invention contain at least one polyhydric alcohol, and more preferably, at least two polyhydric alcohols. Preferably the polyhydric alcohol portion of the compositions of this invention may include one or more polyhydric alcohols such as alkylene glycols and others selected from the following group: glycerin, propylene glycol, butylene glycol, hexylene glycol or polyethylene glycol of various molecular weight and the like and/or combination thereof. More preferably, the compositions of this invention contain a polyethylene glycol; most preferably, the polyethylene glycol may be selected from the following group: polyethylene glycol 400 or polyethylene glycol 300. The compositions of this invention should contain polyhydric alcohols in an amount from about 80% to about 98% by weight of the composition.
In a preferred embodiment, the carrier is a mixture of polyethylene glycol and propylene glycol as described in U.S. Pat. No. 7,005,408, the disclosure of which is hereby incorporated by reference. For example, the polyhydric alcohol is a mixture of polyethylene glycol, for example polyethylene glycol 400, and propylene glycol wherein the weight ratio of polyethylene glycol to propylene glycol is about 3:1.
It has been observed that polyethylene glycols in an anhydrous form degrade much more readily as compared to their aqueous solutions. This degradation of polyethylene glycols can result in the development of a formaldehyde type of odor. Antioxidants may be included to prevent the development of this odor. Examples of suitable antioxidants include α-tochopherol, α-tochopherol acetate, butylated hydroxytoluene (BHT), ascorbic acid, tocopherol and propyl gallate and mixtures thereof and the like as described in copending U.S. patent application Ser. No. 11/403,592, filed Apr. 13, 2006, the disclosure of which is hereby incorporated by reference. The antioxidant may be present for example, in amounts ranging from about 0.05% to about 3% by weight, preferably from 0.05% to about 1.5% by weight.
In one embodiment, the compositions according to the invention may include a sensory agent that provides a cue to the user that vasodilation and/or engorgement that leads to arousal is taking place as described for example in copending U.S. Provisional Patent Application Ser. No. 60/889,062, patent application Ser. Nos. 11/842,487 and 11/842,271, the disclosures of which are hereby incorporated by reference. Examples of sensory agents include methyl salicylate, menthyl lactate and methyl nicotinate.
In one embodiment, the compositions of the invention further comprise at least one sensitivity enhancer to enhance sensitivity. Generally, the sensitivity enhancer may be present in amounts ranging from about 0.05 to about 5% by weight. Although their primary role is sensitivity enhancement, these fall into two separate categories.
The first category of these sensitivity enhancers are cooling compounds, especially non-menthol cooling compounds, such as, described, for example, in Cool Without Menthol & Cooler Than Menthol by John C. Lefingwell, Ph.D., Leffingwell & Associates, Apr. 19, 2007. These include WS-23 (2-Isopropyl-N, 2,3-trimethylbutyramide), WS-3 (N-Ethyl-p-menthane-3-carboxamide) and WS-5 [Ethyl 3-(p-menthane-3-carboxamido) acetate] supplied by Millennium Specialty Chemicals, 601 Crestwood Street, Jacksonville, Fla. 32208-4476, USA. Of these, WS-5 is the “coldest” of commercially available “coolants” and has recently received GRAS approval. Also included is Menthone glycerol ketal (sold as Frescolat® MGA by Haarmann & Reimer). Both the racemic and leavo-forms appear on the FEMA GRAS list but the leavo-form appears to be the item of commerce. (−)-Menthyl lactate (sold as Frescolat® ML by Haarmann & Reimer. Also included is (−)-Isopulegol sold under the name “Coolact P®” by Takasago International.
An example of a second category of sensitivity enhancers are warming compounds that work either by exothermic reaction or by activation of chemoreceptors for heat. These include piperine from Piper nigrum or Black and White Pepper, 1-Acetoxychavicol Acetate, a pungent principal from Alpina Galangal, Shansools, specifically, α-hydroxyshansool from Sichuan pepper and Ginger Extract available from Givaudan Fragrances Corporation, 1775 Windsor Road, Teaneck, N.J. 07666, USA and Timurol, from Napalese pepper, available from Monell Chemical senses Center, 3500 Market Street, Philadelphia, Pa. 19104-3308. These compounds give interesting warming and tingling sensation. Also included in this category is Hesperidin and specifically glucosyl hesperidin supplied by Hayashibara International, Fetcham park House, Lower Rod, Fetcham, Leatherhead, Surrey, KT229HD, U.K
The third category of sensitivity enhancement is tingling compounds that are different from cooling or warming compounds. These compound compounds cause or generate a feeling of buzz or vibration, which is pleasant. These include the following: Shansools, specifically α-hydroxyshansool from Sichuan pepper, distributed by Jivaudan S A, 5, Chemin de la Parfumerie CR-1214 Vernier, Geneve, Switzerland and Spilanthol derived by Jumboo Extract, distributed by Takasago International Group, 4 Volvo drive, P.O. Box 932, Rockleigh, N.J. 07647-0923. These also include Timurol, from Nepalese pepper by Monell Chemical Senses Center, 3500 Market Street Philadelphia, Pa. 19104-3308
Compositions of this invention also include cellulose based lubricating and viscosity agents as described in U.S. Pat. No. 7,005,408, the disclosure of which is incorporated by reference. Examples include carboxymethylcelluloe, hydroxyetylcellulose, hydroxypropyl methylcellulose, especially hydroxypropylcellulose sold under the name Klucel H F, distributed by Aqualon Inc, Delaware. Such cellulose based lubricating and viscosity agents may be incorporated at about 0.05% to about 5% by weight, for example, 0.4% to about 3% by weight.
In one embodiment, the compositions according to the invention contain from about 0.10% to about 0.2% by weight of vasodilator, e.g., niacin derivative, preferably niacin, from about 0.05% to about 1.5% by weight of sensitivity enhancement agent or combination thereof, from about 20% to about 80% polyethylene glycol 400, from about 20% to about 80% of propylene glycol, from about 0.2% to about 1.5% hydroxypropylcellulose and from about 0.05 to about 1.5% or from about 0.05% to about 3%, α-tochopherol, or 0.05 to 1.5% or from about 0.05% to about 3%, α-tochopherol acetate.
The compositions of this invention can be prepared using techniques known in the art for preparing anhydrous compositions. See for example, U.S. Pat. No. 7,005,408, the disclosure of which is hereby incorporated by reference. For example, an acceptable carrier, e.g., propylene glycol and/or polyethylene glycol 400, and optionally a lubricating and viscosity agent, e.g., Klucel HF are mixed at about 50° C. (45° C.-55° C.) until a uniform gel is obtained.
Into the above gel, the vasodilator is added with constant mixing until completely dissolved. Wherever applicable, sensitivity enhancers and other optional ingredients can also be added.
The batch is cooled to room temperature with continued mixing. If desired, antioxidants are and mixed until these completely dissolved.
The compositions of this invention may be applied to the human tissue, for example, the genital region of a male or female, the skin or mucous membranes, preferable the vaginal or oral mucosa as described in U.S. Pat. No. 7,005,408, the disclosure of which is hereby incorporated by reference. The compositions of this invention may be a liquid, a semi-solid, or a solid depending upon the particular intended use thereof. The compositions of this invention may also be formulated into soft or hard gelatin capsules, suppositories and impregnated into fabrics or polymers. Compositions of this invention may be manufactured as a coating of a tampon, or dispersing throughout the absorbent tampon material, or enclosed inside as a core of a tampon.
In one embodiment of the invention, the compositions of the invention are administered between about 5 to about 30 minutes prior to intercourse. Further, it is desired that blood flow in the areas that were treated is restored to the normal blood flow within a short time period, for example, within one hour, preferably, less than an hour after intercourse.
The compositions and methods of this invention unexpectedly result in an increase in the blood flow but do not cause “flushing” of the skin. As used herein, “flushing” is a skin reaction to a topically-applied material which includes the symptoms of redness, swelling, itching and/or irritation at the site of application. Overall interaction of the anhydrous carrier along with the vasodilatation provided by the active vasodilators results in an effective and desired increase in blood flow. The preferred vasodilator used by this invention is niacin or nicotinic acid. As discussed above, in niacin containing aqueous compositions, for example, Vibrel, manufactured by GlycoBiosciences Inc., Campbellville, Canada, there is prolonged “flushing” and redness of the skin and tissues. This is due to the fact that niacin in the composition stays in the exterior layers of the skin.
In the compositions according to the invention, the vasodilatation is controlled because of the amount of vasodilator, such as, niacin derivative, preferably niacin, used (0.1% to 0.5%) and because the unique anhydrous base is responsible for penetration of the vasodilator to the deeper layers of the tissue, which we theorize penetrates at least through the stratum corneum and preferably the epidermis. This results in a desired increase in blood flow without an undesired flushing effect.
In another embodiment the invention relates to the use of Laser Doppler Imaging to measure the blood flow and an increase in the blood flow in the skin. Accordingly, the invention also relates to a method for measuring the efficacy of a composition for improving sexual wellness comprising:
Laser Doppler Imaging (“LDI”) is a technique commonly used to monitor blood flow in the skin. LDI analysis utilizes low power laser light to penetrate the skin (less than about 0.2 mm) and interact with moving blood cells. A photodetector is used to measure the frequency of the backscattered light. Due to the Doppler effect, moving blood cells will cause a frequency change in the backscattered light whereas non-moving tissue will scatter light back at the same frequency. The frequency change is directly proportional to the number of moving cells (blood flow). Using this principle, LDI is used to scan skin areas and results in a two-dimensional skin perfusion image of the skin.
Overall female sexual wellness, or female sexual well-being, may also be measured utilizing a Female Sexual Well-Being (FSWB) Scale. There are five main domains of FSWB that can be measured, including: (1) interpersonal sex, (2) emotional sex, (3) arousal-natural lubrication, (4) orgasm-satisfaction, and (5) artifical lubrication. These domains address four major aspects of Female Sexual Well-Being: (1) physical response and sensation, (2) emotional and cognitive components, (3) contextual factors and (4) communication. It is expected that using the compositions and methods of this invention will improve the FSWB scores of individuals initially scoring low in the five main domains of FSWB and/or maintain FSWB scores of those scoring high in these domains after using the compositions and methods of this invention.
LDI Test Procedure used by this invention utilizes Moor Instruments, MoorLDI2-IR to measure the blood flow in the forearm before and after the application of various test samples. Alternately, the Periscan PIM High Resolution Laser Doppler Imager (HR) by Perimed AB, Box 564, SE-17526 Jarfalla, Stockholm, Sweden can be also used. A suitable amount, for example, from 1 ml to 3 ml of the Test Sample is applied to the forearm and rubbed into the skin lightly for 3 minutes. Compositions of this invention containing higher potency vasodilators may be applied in suitable amount from about 0.1 to about 0.5 ml, more preferably from about 0.2 to about 0.4 ml and most preferably about 0.3 ml.
Samples of compositions to be tested may be applied as follows: Area of forearms between elbow to the upper portion of the hand is washed with soap and water and dried using a paper towel. After waiting for approximately 10 minutes a sample of the composition to be tested is filled to a 3 ml level in a 5 ml plastic syringe. The contents of the syringe may now be carefully expressed over the middle of one of the forearms. Using the index and the middle finger of the other hand the sample is evenly spread over the entire forearm and is gently rubbed over the entire arm for a duration of about 3 minutes. Now the same procedure is repeated for the reference baseline sample over the other arm.
Both arms may now be placed on the platform under the laser beam of the LDI equipment and scanned for a period of 3 minutes.
LDI scanning is normally conducted before sample application as well as 3 minutes after the application of the sample. Because the increase in blood flow results in the engorgement of the tissues, especially the vaginal area, it is most desirable that after the sexual activity, the blood flow is restored to the normal blood flow. To ascertain that normal blood flow is restored, in a special experiment LDI observations of the blood flow were conducted at 0, 15, 35 and 55 minutes after application of the sample, as reported in
Blood flow values are calculated using the LDI Moor image analysis software and average blood flow values (in arbitrary units) is calculated at each time point. A bar graph showing the quantitative blood flow increase after application of formulation is shown, for example, in FIGS. 1,2,4 and 5, 6, 8, and 10 and LDI images are shown in
As discussed above, the compositions according to the invention are non-flushing. Generally, an increase in blood flow that is greater than 300% will cause flushing. Accordingly, in one embodiment, the compositions according to the invention demonstrate an increase in blood flow that is less than 300%, preferably from about 50% to about 150%.
The invention will now be illustrated by means of the non-limiting examples that follow.
The composition of Example 1 was made as follows:
The composition of Example 2 was made as follows:
The composition of Example 3 was made as follows:
As demonstrated by
As demonstrated by
The above composition of Example 4 was prepared as follows:
The above composition of Example 5 was prepared as follows:
The above composition of Example 6 was prepared as follows:
The above composition of Example 7 was prepared as follows:
The above composition of Example 8 was prepared as follows:
The above composition of Example 9 was prepared as follows:
The above composition of Example 10 was prepared as follows:
The above composition of Example 11 was prepared as follows:
1. In the manufacturing container the following were added:
2. Mixed using a Silverson Mixer while heated to about 50° C. (45° C.-55° C.) until a uniform liquid is obtained
3. Cooled to room temperature
The above composition of Example 13 was prepared as follows:
1. In the manufacturing container add the following:
2. Mix using a Silverson Mixer while heating to about 50° C. (45° C.-55° C.) until a uniform gel is obtained
3. Cool to room temperature
The above composition of Example 14 was prepared as follows:
1. In the manufacturing container the following were added:
2. Mixed using a Silverson Mixer while heated to about 50° C. (45° C.-55° C.) until a uniform liquid was obtained
3. Cooled to room temperature
(Excite®, Distributed by Jordyn Nicole)
A bar graph of the blood flow changes from baseline monitored by LDI after 2 ml of the compositions of Examples 11-15 were manually rubbed of the forearm of subjects is set forth in
The above composition of Example 16 was made as follows:
The above composition 17 was made as follows:
The above composition 18 was made as follows:
The above composition of Example 19 was made as follows:
The above composition of Example 20 was made as follows:
Certain patents describe the use of L-Arginine in compositions to enhance sexual response due to the involvement of L-Arginine in the physiological pathway that leads to vasodilation and, ultimately, engorgement of the sexual organs as L-Arginine is a nitric oxide donor. While L-Arginine is a vasodilator in the tissue where Nitric Oxide Synthetase is present, there is no reported evidence that this nitric oxide-generating enzyme in the human male or female sex organs or tissues necessarily relates to the arousal and/or orgasm processes. Surprisingly, we have found that an L-Arginine containing Aqueous composition (as shown in
The above composition of Example 21 was prepared as follows:
The above composition of Example 22 was prepared as follows:
The above composition of Example 23 was prepared as follows:
The above composition of Example 24 was prepared as follows:
The above composition of Example 25 was prepared as follows:
The above composition of Example 26 was prepared as follows:
The above composition of Example 27 was prepared as follows:
Purified water
Methoxypolyethylene glycol
Further,
The right arm for Example 28 (VIBREL®) shows extensive area showing excessive blood flow change representing “Flushing” shown by blue color. This represents change on the superficial skin as compared to deeper layers for right arm represented by red color. Extensive red and blue area of superficial blood flow for Example 28 represents “flushing”, as demonstrated, the total area covered is much more extensive.
Distributed by the Women's Consumer Product, Division of QualiLife Phrmaceuticals, Inc. Charleston, S.C., 29407
Angelica Extract
Coleus Extract
The above composition of Example 30A was prepared as follows:
The above composition of Example 30B was prepared as follows:
The above composition of Example 31A was prepared as follows:
The above composition of Example 31B was prepared as follows:
The above composition of Example 32A was prepared as follows:
The above composition of Example 32B was prepared as follows:
The compositions of Examples 30A, 30B, 31A, 31B, 32A and 32B were applied in the amount of 0.3 ml per application to the forearms of a subject. The blood flow was measured using LDI techniques prior to application, five minutes after application and 30 minutes after application of the compositions of the examples. Redness, irritation, itching of the skin (i.e., “flushing”) was not observed to be caused by any of the sample compositions, even in the cases of Examples 30B, 31B and 32B, in which increased blood flow was observed. The difference in the rate of blood flow was calculated on a percentage basis for each of the sample compositions. The differences after five minutes are set forth in the graph of
The compositions of Examples 22, 30B, 31B, and 32B were applied in the amount of 0.3 ml per application to the forearms of a subject. The blood flow was measured using LDI techniques prior to application, five minutes after application and 30 minutes after application of the compositions of the examples. Redness, irritation, itching of the skin (i.e., “flushing”) was not observed to be caused by any of the sample compositions, even in the cases of Examples 30B, 31B and 32B, in which increased blood flow was observed. The difference in the rate of blood flow was calculated on a percentage basis for the Examples 30B, 31B and 32B sample compositions in relation to percentage increase over Example 22. The differences after five minutes and thirty minutes are set forth in the graph of
Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.
This application claims the benefit of priority of U.S. Provisional Application Ser. No. 60/957,087, filed Aug. 21, 2007 and hereby incorporates by reference the subject matter set forth therein. Related applications include U.S. patent application Ser. Nos. 11/842,487 and 11/842,271, the disclosures of which are hereby incorporated by reference.
Number | Date | Country | |
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60957087 | Aug 2007 | US |