Coated triterpenoid crystal as wavelength dependent sunblock for use in sunblock lotions and skin-toning makeup

Abstract

A triterpenoid composition comprising crystals of triterpenoids (preferably betulin, betulinic acid, lupeol, and salts thereof) suspended in or coated by a carrier comprised of an oil or wax is an effective sunblock and skin emollient. The triterpenoid composition reflects UVA and UVB rays but allows visible light to pass therethrough. The composition matches the refractive index of the coating material to the betulin crystals so the material can have the desired UV reflection while remaining transparent to visible light and allowing beneficial red light to reach the skin. A method of preparation of the sunblock is also provided which allows for the sunblock composition to be created from natural starting materials.

Description

COATED TRITERPENOID CRYSTAL AS WAVELENGTH DEPENDENT SUNBLOCK FOR USE IN SUNBLOCK LOTIONS AND SKIN-TONING MAKEUP CROS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to US App. No. 63 / 770215 filed March 11 , 2025 and entitled “Visibly Transparent Triterpenoid Composition and Method Of Preparation, said application being incorporated herein by reference.FIELD OF THE INVENTION

[0002] This invention relates to visibly clear triterpenoid compositions based on betulin, betulinic acid, and / or lupeol which can be used as sunblock and / or as skin emollients, and methods of preparing the triterpenoid compositions. More particularly, this invention relates to betulin crystals coated with materials of specific refractive indices to create a sunblock that selectively reflects UVA and UVB light while remaining transparent to visible light and beneficial red light.BACKGROUND OF THE INVENTIONThe Effect of Sunlight on Human Skin

[0003] Sunlight reaching Earth spans wavelengths from 300nm to 2500nm, but the biologically relevant portion for skin health ranges from 280nm to 800nm. In general, higher energy (shorter wavelength) light is more biologically damaging, while longer wavelength light can be biologically beneficial. The sunlight in the 280nm to 800nm range is divided between UVB, UVA, and the visible spectrum (violet light through red light), as follows:

[0004] UVB light (280nm-315nm) causes direct DNA damage and is primarily responsible for sunburn, skin peeling, and increased skin cancer risk. UVA2 light (315nm-340nm) produces similar damage but penetrates deeper into the skin, damaging collagen and skin elasticity; it is also 2-10 times more intense than UVB. UVA1 light (340nm-400nm) contributes to skin cancer indirectly through free22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2radical generation and immune suppression, and is a major contributor to photoaging.

[0005] In the visible spectrum, violet-blue light (400nm-500nm) causes pigmentation and oxidative stress contributing to skin aging. Green through orange light (500nm-620nm) is relatively neutral. Red light (620nm-700nm), however, is beneficial. Red light increases cellular ATP, supports cell function, promotes healing, and improves collagen signaling.Limitations of Conventional Sunblocks and Sunscreens

[0006] Currently available sunblocks are topical compositions containing mineral particles - typically zinc oxide (ZnO) or titanium dioxide (TiO2)-that reflect and scatter UV radiation to protect skin. These minerals do not absorb visible light, yet they appear white due to their extremely high refractive indices (2.60 for TiChand 2.00 for ZnO). At normal incidence, ZnO reflects 11% of yellow light and TiO2 reflects 20% of yellow light, with reflection increasing at oblique angles. Critically, these materials reflect beneficial red light at nearly the same rate as harmful UV light.

[0007] As illustrated in FIGS. 1A and 1B, effective UV protection using mineral particles requires complete skin coverage with the mineral particles, which results in an opaque white appearance. Consumers typically apply reduced concentrations for cosmetic acceptability, but this leaves gaps where UV light penetrates unimpeded. Nanosized particles can achieve transparency to visible light while still reflecting UV, but zinc oxide nanoparticles have been shown to be harmful to marine ecosystems.

[0008] In contrast, sunscreens utilize organic (chemical) filters such as avobenzone, octinoxate, or oxybenzone that absorb UV photons and convert them into heat or chemical energy. While sunscreens offer transparent application and formulation versatility, they present significant concerns. The absorbed energy can generate free radicals that damage skin cells. As of 2021 , the FDA does not classify any chemical sunscreen filter as generally recognized as safe and effective (GRASE) - only zinc oxide and titanium dioxide hold that designation.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

[0009] Sunscreens also exhibit limited photostability, requiring frequent reapplication as they photoconvert into potentially toxic byproducts. A 2019 FDA study demonstrated that chemical sunscreens applied at recommended levels result in systemic absorption exceeding FDA safety thresholds. Additionally, avobenzone, oxybenzone, and octinoxate have been shown to damage marine ecosystems, leading several jurisdictions including Hawaii, Australia, and Thailand to ban certain sunscreen formulations.

[0010] Accordingly, physical sunblocks remain the safest and most effective means of UV protection, but their opacity limits consumer acceptance. There exists a need for a sunblock composition that provides strong, uniform UV protection while remaining optically transparent and, ideally, functioning as a skin emollient for daily use. Further, the subblock composition preferably blocks UVB and UVA light while being generally transparent to red light (so that red light can pass through the sunblock composition).SUMMARY OF THE INVENTION

[0011] Disclosed is a visibly clear triterpenoid composition usable in sunblock compositions, in skin-toning makeup, or as an emollient. A method for making the triterpenoid composition is also disclosed. The triterpenoid composition comprises crystalline particles of betulin, lupeol, or betulinic acid that are dispersed in or coated with a substantially clear medium, such as oil or wax. The crystalline particles have a refractive index sufficiently different from the medium so that high energy, short wavelength UV light is scattered by the particles, but longer wavelength visible light is not, such that red light can pass through the triterpenoid composition.

[0012] The refractive index refers to the speed of light through the medium relative to its speed in a vacuum. The refractive index of air is set at 1.00; and the refractive index of water is 1.33. Thus, speed of light in water is 1 / 1.33 = 0.75 times the speed of light in air (or stated differently, light travels 1.33 times faster in air than it does in water). It is well known that light is reflected from surfaces which have different refractive indexes, which is why light reflects from water. The percentage of the light that is reflected22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2increases as the angle of incidence increases. The reflection is also stronger for shorter wavelength light than it is for longer wavelength light.

[0013] The disclosed triterpenoid composition relies on the reflectivity of, in particular, UV light, off surfaces with different refractive indexes, and the fact that this reflection is strongest with highly crystalline materials, to create a triterpenoid composition which is opaque to short wavelength UV light but substantially transparent to longer wavelength visible light. Thus, the triterpenoid composition is visibly clear.

[0014] The triterpenoid composition comprises crystals of triterpenoids (preferably betulin, betulinic acid, lupeol, betulin derivatives, salts thereof, or combinations thereof) as active ingredients which are suspended in, or coated with, a medium having a refractive index close to but not exactly the same as betulin, such as a triglyceride oil or jojoba oil (which is a liquid wax). The betulin and betulinic acid may be present in a ratio of 1.0:99.0 to 99.0: 1.0, and the betulin and lupeol may be present in a ratio of 0.5:98.5 to 98.5:0.5.

[0015] The triterpenoids are preferably derived from the bark of white birch trees. For example, the birch bark can be from any of the genus Betula, but is preferably from Betula Alba (White Birch), Betula Pendula (Silver Birch), Betula Neoalaskana (Alaskan Birch), or Betula Papyrifera (Paper Birch) because of their high concentration of betulin in their bark. The triterpenoids make up 20-40% of the bark of these trees. The relative ratio of the triterpenoids in the triterpenoid composition is determined, in part, by their respective relative ratios in the birch bark from which they are extracted. The refractive index (Rl) of these triterpenoids - betulin (Rl of 1.51 ), lupeol (Rl of 1.52), and betulinic acid (Rl of 1.57) - are close enough that the relative ratio of the different triterpenoids in the triterpenoid composition is not material to the effectiveness of the triterpenoid composition as a sunblock.

[0016] The medium in which triterpenoid crystals are suspended or with which they are coated has a refractive index close to but not exactly the same as betulin. Triglyceride oil (Rl of ~1.45) or jojoba oil (a liquid wax with an Rl of ~ 1.45), almond oil (Rl of ~1.46) and beeswax (Rl of ~1.44) are acceptable carrier media.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

[0017] The triterpenoid crystals preferably have an average size of at least 400nm, and more preferably an average size of about 800nm to about 10 microns. The crystals of triterpenoids or triterpenoid salts have a refractive index of about 1.45 to about 1.55, and the medium has a refractive index of about 1.40 to about 1.49. In certain embodiments, the refractive indices of the crystals and the medium are within about 10% of each other. The crystals of the triterpenoids may comprise about 0.5% to about 95.5% by weight of the composition, and preferably about 3% to about 20% by weight.

[0018] Betulin, betulinic acid, and lupeol are chosen because their refractive index is slightly higher than most oils and waxes, and they are very crystalline with a very high melting point (over 200°C) and very low solubility in water, organic solvents, or oils. Their high crystallinity creates many surfaces extending in various directions and planes, resulting in a high percentage of reflection of UV light. The high melting point and low solubility of the triterpenoid crystals ensures that the crystals will remain intact and will not dissolve in oils or in water or sweat (which is essentially aqueous) and they will not melt during a milling process, which is common when producing lotions.

[0019] The triterpenoid composition reflects UV radiation, including UV-A and UV-B light and thus is opaque to UV radiation while being substantially transparent to visible light, making the composition an effective sunblock. The triterpenoid crystals need to be suspended in, or coated with, an oil or wax carrier which is at a minimum 800nm thick, ensuring direct contact between the betulin triterpenoid and the oil or wax carrier.Preferably, the thickness of the oil or wax carrier is at least as wide as a wavelength of sunlight.

[0020] The composition also acts as an emollient that softens and moisturizes skin, and thus the composition can be used in make-up compositions (such as skin toning makeup and lipstick). The composition has been found to remain effective for a particularly long time, up to several days. Additionally, the composition remains on the skin even after swimming in water or taking a shower. Thus, when used as a sunblock, the composition will not need to be reapplied as often as a Zn- or Ti-based sunblock.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

[0021] The triterpenoid composition can be prepared by extracting the triterpenoids from birch bark using a solvent (such as dimethyl carbonate, diethyl carbonate, or acetone), adding an oil, and distilling the resulting mixture to drive off the solvent, leaving the active ingredients (i.e. , the triterpenoids) suspended as crystalline solids in the oil.Alternatively, the triterpenoids can be extracted and distilled to form a powder, which can then be added to the oil or wax. The extraction step may be performed by soaking the birch bark in the extraction solvent or by refluxing the extraction solvent through the birch bark, preferably until white matter is substantially no longer visible in the birch bark. The method of preparation can also include a post-treatment step after distillation, such as milling the crystalline nanoparticles to achieve a desired range of nanoparticle sizes and / or shapes.

[0022] The triterpenoid crystals may be produced in high purity, having less than 1 % tannins or other phenolics, by extracting botulin from the outer bark of Betula Papyrifera, Betula Neoalaskana, Betula Pendula, or Betula Platyphylla with dimethyl carbonate or diethyl carbonate, and condensing the solvents to yield the triterpenoid crystals.

[0023] In another method, the triterpenoid crystals may be coated with a coating media having a low refractive index by dispersing the triterpenoid crystals and the coating media in a solvent, such as dimethyl carbonate, in which the triterpenoid crystals are less soluble than the coating media, and subsequently evaporating the solvent, wherein upon evaporation of the solvent, the triterpenoid crystals crystallize first and the coating media coats the outside of the crystals. Alternatively, triterpenoid crystals may be coated by extracting triterpenoid from white birch bark using dimethyl carbonate or ethyl carbonate and subsequently evaporating the dimethyl carbonate or ethyl carbonate to yield coated triterpenoid crystals.BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The drawings described herein are for illustration purposes only and are not intended to limit the scope of the present teachings in any way;22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

[0025] FIG. 1 A is a diagram showing sunlight being reflected away from skin protected by a ZnO and TiC based sunblock;

[0026] FIG. 1 B is similar to FIG. 1A, but demonstrates sunlight penetrating the ZnO and TiO? based sunblock when the ZnO and TiO2 particles do not properly or fully cover the skin;

[0027] FIG. 2 includes four microscopic images of betulin crystals showing their needlelike faceted surfaces;

[0028] FIG. 3 shows a quantity of white birch bark prior to extraction of betulin from the bark;

[0029] FIG. 4 shows the white birch bark after extraction of the betulin;

[0030] FIG. 5 is a diagram of sunlight impacting the triterpenoid composition, showing UVA and UVB rays being reflected away from the skin, but visible light passing through the composition;

[0031] FIG. 6 shows betulin crystals uncoated (left) and betulin crystals coated with almond oil (right) on a human finger, demonstrating the transparency achieved through coating;

[0032] FIG. 7 shows jars of uncoated betulin crystals (top, appearing white) and crystals coated with almond oil (bottom, appearing tan / orange);

[0033] FIG. 8 shows the reflection spectrum for ultraviolet and visible light from 290nm to 400nm for pure almond oil (bottom line), almond oil with 10% betulin crystals (middle line), and almond oil with 20% betulin crystals (top line), the triterpenoid compositions being made as described in Example 2; and

[0034] FIG. 9 shows betulin crystals coated with isopropyl laurate, demonstrating a bolder orange / tan color than crystals coated with almond oil.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

[0035] Corresponding reference numerals indicate corresponding parts throughout the several views of drawings.DETAILED DESCRIPTION OF THE INVENTION

[0036] The following detailed description illustrates the claimed invention by way of example and not by way of limitation. This description will clearly enable one skilled in the art to make and use the claimed invention, and describes several embodiments, adaptations, variations, alternatives, and uses of the claimed invention, including what is presently believed to be the best mode of carrying out the claimed invention.Additionally, it is to be understood that the claimed invention is not limited in its application to the details of construction and the arrangements of components set forth in the following description or illustrated in the drawings. The claimed invention is capable of other embodiments and of being practiced or being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.Betulin and Its Properties

[0037] Betulin is nature's sunblock. It is the white crystals that cover the outer bark of white birch trees. This species of deciduous tree grows predominantly in cool temperate regions of the world. During the winter they lose their leaves and the sap stops running. However, if there is a sudden warming trend with lots of sunlight in the wintertime, the sap of birch trees will begin to run. The problem is that if the weather suddenly turns cold, the sap will freeze, expand, and crack the tree. Consequently, birch trees have evolved to produce white crystals that act as sunblock for the tree so the sap does not run during winter.

[0038] These crystals predominantly (usually over 80%) consist of a triterpenoid called betulin. With the betulin there are other similar triterpenoids such as betulinic acid (usually about 10%) and lupeol (usually about 5%). All three have similar melting points, refractive indexes, and solubilities. For the purposes of this description, this crystals of betulin, betulinic acid, and lupeol are collectively referred to simply as "betulin crystals."22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

[0039] The chemical structures for betulin, betulinic acid, and lupeol are provided below:

[0040] Betulin, betulinic acid, and lupeol are all water-insoluble triterpenoids, and as such have carbon skeletons that are based on six isoprene units arranged into multiple contiguous rings.

[0041] All three of these triterpenoids have a refractive index of approximately 1.51 at yellow light (~570-590nm). The percent reflectivity of a betulin crystal with normal incident yellow light in air is 4%. Despite their relatively low refractive index and resulting percentage reflection, betulin crystals are still highly reflective of light. Just like snow, rather than being white because of an extremely high refractive index, they get their whiteness from the highly complex, needlelike faceted surfaces which light reflects off. FIG. 2 includes microscopic photograph of betulin crystals, showing their complex faceted surfaces. Betulin crystals are essential for this invention because they have a combination of key properties. They have a high refractive index that averages about 1.51 in the visible range of light, with the refractive index increasing from 1.49 in the blue to 1.52 in the red, and increasing dramatically through the UVA and UVB range of light. Betulin crystals are optically transparent from 290nm to 750nm, exhibit high crystallinity with the ability to form needlelike crystals with many surfaces or facets, have a high melting point of 256°C and a high boiling point of 285°C, and possess a strong crystalline lattice that makes them poorly soluble in both organic solvents and water. Their strong crystalline structure along with high melting point and low solubility makes them difficult to amorphize in any solvent or material. Because of these properties, highly crystalline betulin can be milled and heated while being immersed in solvents or22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2water formulas without deforming. Betulin crystals act like silica, graphite, or other inorganic pigments. These properties also enable the betulin crystals to be coated with or immersed in a wide variety of materials without dissolving into, or becoming amorphous.The Physics of Reflectivity

[0042] Light reflects from surfaces which have different refractive indices. The percentage of the light that is reflected increases as the angle of incidence increases. Light reflects off a smooth surface of water, but some light also passes through the water. However, at a more glancing angle (i.e. , a larger angle of incidence), more light is reflected. Snow, which is frozen water, is white and much more opaque than a pool of water, because snow is very crystalline and light reflects off the many different surfaces so absolutely no visible light gets through highly compacted snow. This reflection is strongest with shorter wavelength blue and UV light. Thus, if one looks at deep snow, it appears blue because shorter wavelength blue light is being reflected more than longer wavelength visible light.

[0043] The equation describing the percentage of light reflected from the interface between two clear materials with different refractive indexes is the Fresnel Reflection Equation, i.e.,where n1and n2are the refractive indices of the two materials.

[0044] The Fresnel Reflection Equation specifically describes light of normal incidence (light shining directly at 90° to the plane of the interface). Consequently, with light shining straight down onto the surface of water or ice (which have a reflective index of 1.33) and with air (which has the refractive index of 1.00), the percentage of reflectance is 2%. But if the light is traveling straight through a crystal of ice, it reflects 2% as it enters the ice crystals and 2% more as it exits the ice crystals.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

[0045] The refractive index of a material is wavelength dependent because higher frequency light (higher energy) is affected more by materials. With most materials there is a slight increase in refractive index in the visible spectrum from red to blue. For water, the refractive indexes are: 1.343 for blue light, 1.333 for yellow light, and 1.331 for red light. At normal incidence, the reflection is therefore: 2.08% for 486nm blue light, 2.04% for 589nm yellow light, and 2.01% for 656nm red light.

[0046] The effect of reflection is amplified when the incidence of light is at an angle because the percent reflection is also dependent on the angle of incidence of the light. The reflection is higher at larger angles, and because the refractive index is higher for higher energy light, the difference in reflection is larger. For example, at an incidence of 45° to the plane of water, the reflection is: 6.26% for 486nm blue light, 6.13% for 589nm yellow light, and 6.09% for 656nm red light. If light enters an ice crystal at 45° and then passes through the backside at 45°, only 90% of the original yellow light component makes it through the crystal. But that is only one ice crystal; after the light passes through 100 ice crystals at the same angle, the percentage of light making it all the way through without being reflected is 0.3%. Because there are so many air / ice interfaces in snow, and they are at many different angles, only a few millimeters of snow are required for it to reflect all light and appear white.The Triterpenoid Sunblock Composition

[0047] As has been noted, the triterpenoid sunblock composition is comprised of triterpenoid crystals suspended in, or coated with, a clear hydrophobic carrier medium, such as an oil or wax, which can be used as a sunblock, in make-up, or as a skin emollient. Preferably the refractive index of the carrier medium is close to (i.e., within 10% of) the refractive index of the triterpenoid crystals. For example, the crystals, and thus the carrier medium, can have a refractive index of about 1.45 to about 1.55 and the carrier medium can have a refractive index ranging from 1.40 to 1.49. The sunblock composition is visibly clear and will selectively block UVB and UVA light while allowing visible light (including red light) to pass through. Consequently, unlike sunblocks such as titanium dioxide or zinc oxide, a large amount of a betulin-based sunblock can be22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2used without coloring the skin. The coated crystals are stable to formulation processing and are stable in water-based lotion formulations. The triterpenoid crystals may range from 80-90% betulin, 8%-12% betulinic acid, and the remainder (though no more than 8%) is lupeol. The Rl of all three triterpenoids is 1.51 and their combination is 1.51.

[0048] As used herein, "visibly clear", “generally clear”, and "substantially clear" means that when the sunblock composition is applied to skin, the skin is visible through the triterpenoid composition. "Visibly clear" and "substantially clear" does not necessarily mean that the triterpenoid composition is fully transparent. Preferably, the triterpenoid crystals are crystals of betulin, betulinic acid, a betulin derivative, and / or lupeol, which, preferably, are extracted from the bark of trees of any of the genus Betula, but are preferably from Betula Alba (White Birch), Betula Pendula (Silver Birch), Betula Neoalaskana (Alaskan Birch) or Betula Papyrifera (paper birch) because of their high concentration of betulin in their bark.

[0049] Because the refractive index of air (1.00) is so different from the refractive index of betulin (1.51), and because the betulin crystals have surfaces pointed in many directions, the betulin crystals appear white. If the betulin crystals are dispersed in a material with a refractive index of 1.51 , the light would not be reflected and the material would look clear. If betulin crystals are coated with a material that has an appropriate Rl, only high energy light is reflected whereas visible light passes through the crystals. By using the right material with an appropriate Rl, the coated or immersed betulin crystals can reflect high energy UVA, UVB, violet, and / or blue light, while allowing longer wavelengths of light (i.e. , red light) to pass through. This is ideal for use in a sunblock or sunscreen lotion. Not only is the lotion optically transparent, but the yellow, orange, red, and infrared light that passes through is known to be beneficial to the skin.

[0050] The relatively low refractive index of betulin enables betulin crystals to be coated with a material that makes the resulting composition transparent to visible light, but highly reflective to UVA and UVB light. For example, if betulin crystals are coated with a fine layer of almond oil, which has a refractive index of 1.47, the normal reflection of22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2yellow light is reduced dramatically to 0.02%. Thus, the resulting composition is generally transparent or substantially transparent to yellow light.

[0051] The uneven reflectivity, and therefore orange / tan color when betulin crystals are coated with almond oil, reveals the fact that the refractive index for betulin is higher for violet / blue light than it is for yellow / orange / red light. As discussed above, this is common for all materials. It is also known that the refractive index often goes up strongly as the wavelength approaches an absorbance. Betulin, betulinic acid, and lupeol all have strong UV absorbances at 210nm, but also smaller absorbances at 275nm that carry out to 350nm. These absorbances cause the refractive index to increase dramatically in the UVB and UVA range. For example, if the refractive index of betulin crystals is 1.7 at 325nm (UVB light), the percent reflection of normal incident light at that wavelength is 2.3%. And because high energy light is more sensitive to the angle of incidence, the reflectance of betulin crystals is dramatically higher for UVB and UVA light than for visible light.

[0052] Testing has confirmed that although the betulin crystals coated with almond oil reflect much less 400nm light than they do 325nm light, they still reflect much more at 400nm than pure almond oil reflects. The pure almond oil has absolutely no reflection until 300nm; however, the samples containing betulin are nearly transparent at 400nm, but there is a strong reflection of light that steadily increases throughout the UVA1 range of 340nm-400nm and peaks at UVA2 of 315nm-340nm. The reflection is very strong throughout the UVB range of 290nm-315nm.

[0053] The gradual decrease in reflectivity seen in the violet range (380nm-400nm) continues throughout the visible light range and is the reason for the tan color of the coated betulin crystals. This suggests that by coating the betulin crystals with different materials with slightly different refractive indexes, it is possible to achieve slightly higher reflectivity in the visible range and have a material that is somewhat transparent but is a deeper tan and could match, or even improve, the tone of skin.

[0054] Advantageously, when applied to skin, the triterpenoid composition is transparent to visible light (i.e. , the user's skin is visible through the triterpenoid composition), yet 22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2the triterpenoid composition still blocks IIV-A and UV-B light from reaching the user's skin due to the unique crystalline properties and the relative refractive indices of the triterpenoid crystals relative to the surrounding oil or wax medium. The composition thus forms a high SPF sunblock. This oil or wax medium forms a carrier for the triterpenoid crystals. The triterpenoid crystals share some similarity with crystals of snow in that they have many surfaces arranged in various directions. Both snow and triterpenoid crystals appear white because impinging photons of light reflect both internally and externally off the snow or triterpenoid crystal structures. The reflection is due to the large difference in refractive indices between the triterpenoid crystals and the surrounding air.

[0055] The triterpenoid combination extracted from birch bark has, on average, a refractive index around 1.55, while the refractive index of air is 1. This large difference in refractive indices at the interface between betulin in birch bark and the air causes visible photons to reflect off the betulin, resulting in a white appearance of the birch bark.However, almond oil's refractive index is approximately 1.45, which is much closer to the refractive index of the betulin crystals. Therefore, when the crystals of the triterpenoids from birch bark are suspended in oil or wax as in the triterpenoid composition described herein, the refractive index change at the surface of the triterpenoid crystals is much smaller (1.55 to 1.45) than it is when the triterpenoids are exposed to air (1.55 to 1). Thus, photons in the visual spectrum can pass through the triterpenoid composition without being reflected off the crystals, making the triterpenoid composition generally transparent when applied to skin, so that the skin will be visible through the triterpenoid composition.

[0056] Figure 6 demonstrates how the appearance of betulin crystals are changed when coated with a small layer of almond oil. In FIG. 6, left image, a finger is coated with pure betulin crystals, revealing its white appearance. In the right image, a finger is coated with pure betulin crystals combined with 30% by weight of almond oil. The crystals supported in a carrier medium of almond oil (FIG. 6, right) are transparent to the eye.

[0057] FIG. 5 diagrammatically shows sunlight SL impinging on the triterpenoid composition SB formed as described herein. The shorter wavelength UVA and UVB rays are reflected22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2away from the skin by the crystals C in the triterpenoid composition SB, but visible light VL is allowed to pass through. Traditional TiC>2 or ZnO based sunblocks, on the other hand, appear murky and white because both UV and visible photons readily reflect off TiO2 and ZnO crystals and because the traditional sunblocks require TiO2 or ZnO crystals larger than the triterpenoid crystals of the disclosed triterpenoid composition. Thus, the triterpenoid composition made from triterpenoid crystals does not have the murky white appearance characteristic of traditional ZnO and TiO2-based sunblocks, and the user's skin does not appear white or pale when the betulin-based triterpenoid composition is used. Rather, the user's skin will be visible through the triterpenoid composition. The concentration and size of the triterpenoid crystals dispersed in the oil is such that they are not perceptible to human touch, making the sunblock feel smooth and comfortable.

[0058] If higher-concentration samples are observed, the uncoated betulin crystals look like white powder whereas the almond-oil-coated crystals look orange / tan. The appearance of an orange / tan color is due to uneven reflectivity through the visible range of light, with high energy blue light being reflected more than the lower energy red / orange / yellow light. What is seen is white light minus a little violet blue light, which is orange / tan. The underlying phenomenon is the same reason the sunset appears orange and red.

[0059] Figure 7 shows a jar of the uncoated betulin crystals on the top and crystals coated with almond oil (100g) betulin crystals coated with 30g almond oil) in the jar below it. The uneven reflectivity, and therefore orange / tan color when betulin crystals are coated with almond oil, reveals the fact that the refractive index for betulin is higher for violet / blue light than it is for yellow / orange / red light. As discussed above, this is common for all materials. It is also known that the refractive index often goes up strongly as the wavelengths approach an absorbance.

[0060] This suggests that by coating the betulin crystals with different materials with slightly different refractive indexes, one can achieve slightly higher reflectivity in the visible range and have a material that is somewhat transparent but is a deeper tan and could match, or even improve the tone of skin. For example, isopropyl laurate is a22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2molecule that is often used in the cosmetics industry for softening skin. It is not volatile (boiling point of 280 °C), it is not soluble in water, and it has a refractive index of 1.43. The percent reflectivity of yellow light from betulin crystal coated with isopropyl laurate is therefore 0.07%.

[0061] Though the refractive index is only slightly lower than almond oil (1.47), it provides 3.5 times the reflection of yellow light when coated on the betulin crystals. This has been observed to be highly amplified by the high crystallinity of the betulin crystals. Figure 9 is an photograph of betulin crystals coated with isopropyl laurate. Its color is much more of a bold orange / tan than the crystals coated with almond oil. Use of isopropyl laurate coated betulin crystals could give significant protection from UVA light and violet and blue light while still allowing some red light through. Consequently, by coating betulin crystals with materials of appropriate refractive index, a sunblocking powder can be designed that blocks UVA and UVB light, but is transparent to visible light. It can also be designed to create a make-up powder that smooths the skin tone, while also enabling beneficial red light to go through.Concentration of Triterpenoid Crystals

[0062] The concentration of the triterpenoid crystals in the triterpenoid composition can vary from 0.01% weight-to-weight percentage (w / w) to 99.99% w / w. The concentration can be in a range from about 0.05% to about 35% w / w, about 0.1% to about 20% w / w, about 0.5% to about 10% w / w, about 1% to about 5% w / w, or about 3% w / w to about 20% w / w. The concentration can be 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25% w / w. The concentration of the triterpenoid crystals, and their small size, in the oil medium can be low enough for the triterpenoid crystals to be barely perceptible to human touch. When the concentration is approximately 20% or higher, the triterpenoid crystals are perceptible to human touch and the triterpenoid composition feels gritty. The concentration must be high enough for the triterpenoid composition to be effective as a sunblock; thus, the concentration of triterpenoid crystals is preferably not lower than 3%.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2Carrier Medium

[0063] The medium is described above as almond oil, but the oil can be any oil, wax, or other medium with a refractive index close to (i.e. , within about 10% of) the refractive index of the triterpenoid crystals. Thus, the oil or wax preferably has a refractive index of about 1.45 to about 1.49. The medium should not contain chemical functionality that absorb UV light substantially above 350nm, as this will cause the refractive index in the UV range to increase. It is important that the refractive index of the betulin increases more than the medium in the UV range. Additionally, the medium can be one in which the triterpenoid crystals cannot dissolve and which supports the suspension of the triterpenoid crystals. Also, the medium ideally will have low volatility, (with a boiling point above 200 °C ) so it does not evaporate quickly when applied to skin).

[0064] For example, the oil can be a naturally-derived oil such as almond oil, avocado oil, argan oil, coconut oil, or any oil that has emollients which help skin retain moisture when exposed to the sun. Other possible oils include grapeseed oil, olive oil, sunflower oil, safflower oil, isopropyl myristate, shea butter, or any combination thereof. The medium can also be a wax, such as jojoba oil, carnauba wax, or beeswax. Additionally, the oil or wax can be a synthetic oil, or any combination of synthetic and natural oils, as long as the oil is transparent to visible light, has a refractive index close to that of the crystals, and is known to be generally safe (GRASE) for use on skin. As noted above, the triterpenoid crystals have a refractive index of about 1.45 to about 1.55; thus, the medium preferably has a refractive index of about 1.40 to about 1.49, which is about ±10% of the refractive index of the triterpenoid crystal.

[0065] For example, isopropyl laurate is a molecule that is often used in the cosmetics industry for softening skin. It is not volatile (boiling point of 280°C), it is not soluble in water, and has a refractive index of 1.43. Though the refractive index is only slightly lower than almond oil (1.47), it provides 3.5 times the reflection of yellow light when coated on the betulin crystals. This is highly amplified by the high crystallinity of the betulin crystals. Use of isopropyl laurate coated betulin crystals could give significant protection from UVA light and violet and blue light while still allowing some red light22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2through. Consequently, by coating betulin crystals with materials of appropriate refractive index, a sunblocking powder can be designed that blocks UVA and UVB light but is transparent to visible light. It can also be designed to create a make-up powder that smooths the skin tone while also enabling beneficial red light to go through.

[0066] The liquid or solid oil or wax should have a refractive index of from about 1.40 to about 1.47 and preferably about 1.45 to about 1.47. This is close to the refractive index of about 1.45-1.55 of the triterpenoid crystals. It is also preferable to use an oil or wax with a smoke point less than the melting point of the triterpenoid crystals, and preferably less than 200°C. For example, almond oil, avocado oil, or beeswax can be used. This reduces smoking of the initial composition during the milling process. The triterpenoids have a melting point of over 250°C so the crystals in oil or wax can be milled to the desired size without fear of the heat of milling causing the crystal structure to melt. The mill can be a steel ball mill, a horizontal mechanical mill, or a vertical mechanical mill.Emollient and Skin Benefits

[0067] The use of these waxes or oils as the carrier for the triterpenoid crystals enables the composition to also act as a skin emollient. In fact, because the composition is essentially clear, the composition can be applied daily as a skin emollient or moisturizer which will also provide UV protection to the skin via its sun-blocking qualities. Further, it has been found that the composition will remain in place even after swimming, bathing, or washing. This is believed to be due to betulin's very low solubility in water or other solvents, as well as its adhesion to the skin and resistance to abrasion. The composition can thus remain on the skin and effective as both an emollient and a sunblock for a particularly long time-not just hours, but all day, and even several days. Thus, the composition will not need to be reapplied as often as a Zn- or Ti-based sunblock or chemical-based sunscreens.

[0068] Betulin crystals have a unique opportunity as a sunblock because they have been shown to be beneficial for the skin. Betulin has been shown to enhance skin barrier repair by stimulating keratinocyte differentiation and supporting epidermal regeneration. It has anti-inflammatory effects by downregulating inflammatory 22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2mediators. It has been shown to promote wound healing by accelerating re- epithelialization and improving wound closure. It has also been shown to help mitigate oxidative stress in damaged skin. Topical birch bark extracts rich in betulin have been tested in small clinical studies to help heal superficial wounds, burns, laser-treated skin, and irritated and inflamed skin conditions. The results in general show improved healing time, better skin appearance, and good tolerability. Betulin has also been shown to be an excellent emollient for the skin.

[0069] Betulin crystals have a refractive index of 1.49 on the blue end of the visible spectrum and 1.52 on the red end, averaging at about 1.51. This refractive index increases significantly through the UVA and UVB wavelengths. This is amplified by a UV absorption band for the olefin at 250nm and 270nm for the carboxylic acid of betulinic acid. From 290 nm to 750 nm wavelengths, betulin crystals are substantially transparent. Betulin crystals show high crystallinity and manifest needle-like crystalline structures with many facets. They have a high melting point around 256 °C and a thermal decomposition point at around 285 °C. Their strong crystalline lattice makes them poorly soluble in organic solvents and water, so they are difficult to amorphized in any solvent or material.

[0070] Thus, highly-crystalline betulin can be milled and heated while being immersed in solvents or water formulas without deforming. In this way, betulin crystals act like silica, graphite or other inorganic pigments. These properties also enable the betulin crystals to be coated with or immersed in a wide variety of materials without dissolving into, or becoming amorphous. Additionally, betulin, betulinic acid and lupeol have all been found to have benefits when topically applied to the skin. These benefits include being anti-inflammatory, wound-healing and anti-carcinogen.METHODS OF PREPARATIONExtraction of Triterpenoids from Birch Bark

[0071] The triterpenoid composition is prepared by extracting triterpenoids (betulin, betulinic acid, and lupeol) from the white material of the bark of white birch trees. The22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2birch bark can be acquired directly from birch trees or from secondary sources such as lumber mills. For the extraction of the triterpenoid, the birch bark can assume various forms. Preferably, the birch bark is sized and shaped for undergoing extraction by a solvent. For example, the birch bark can comprise peels that can be between 1-20 square inches, as seen in FIG. 3. Alternatively, the birch bark can be formed as small chunks or ground to be a powder.

[0072] Betulin, betulinic acid, and lupeol are extracted from the white material of the white birch tree bark using slightly polar, or nonpolar, organic solvents. This avoids the extraction of low molecular weight tannins that are only soluble in water and very polar organic solvents. However, some higher molecular weight tannins will be extracted because they are more soluble in organic solvents. Avoiding tannins is desirable because they absorb sunlight and therefore act as a sunscreen rather than as a sunblock.

[0073] Acetone has been found to have desirable solubility parameters. Acetone is polar enough to extract the triterpenoids when they are diluted. The high molecular weight tannins are more soluble in the acetone, so as the solvent is removed (distilled or evaporated) and the triterpenoid crystals begin to form, the high molecular weight tannins remain in solution. The extracted triterpenoids can then crystallize when the solution becomes more concentrated. Consequently, the triterpenoid crystals, with substantially no tannin contamination, can be filtered away. Acetone also permeates the birch bark at room temperature very well and has a very low boiling point of 56°C, so it is easy to remove acetone from the extracted triterpenoids without melting triterpenoid crystals.

[0074] The outer part of birch bark which is highest in betulin is called the rhytidome. It comprises layers of paper-like bark, which when peeled apart reveals betulin between the layers. A preferred way to ensure the vast majority of the betulin of the rhytidome is removed is to soak the bark in acetone at room temperature. Enough acetone is used to cover the bark. Because the bark is less dense than the acetone, the bark will float and thus needs to be physically submerged. This can be accomplished with a weight, a22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2porous plate which presses down on the bark, or any other desired method of submerging the bark in the organic solvent. The bark is submerged in the acetone until the bark has turned from white to brown, at which point the bark typically will have curled and the layers of bark have separated.

[0075] The curling of the bark, as seen in FIG. 4, is indicative of the fact that the betulin between the layers of bark has also been removed. Betulin has a lower density than acetone; thus, as the triterpenoids are extracted from the bark and enter the solvent, the bark will become denser than the acetone and will sink rather than float. Thus, sinking of the bark within the solvent can also be indicative of the fact that the triterpenoids have been substantially extracted from the bark.

[0076] Generally, the extraction requires 24 hours; however, the bark can be left to sit in the acetone for any desired amount of time (such as days, weeks, or even months). This room temperature extraction has been found to achieve the best results. Extraction could also be accomplished by other methods. For example, the extraction could be accomplished with heat using a Soxhlet extractor, but only the betulin on the outer bark would be removed. Therefore, using a Soxhlet extractor is less efficient and requires more energy (making it more expensive). Extraction at room temperature by soaking the birch bark in the solvent is also cheaper because it is less labor intensive and less energy intensive.

[0077] When the extraction is finished, the bark is filtered from the solvent (acetone) solution using, for example, a 100 micron to 500 micron filter, forming a filtrate that will be a clear brownish color and will contain triterpenoids and any dissolved high molecular weight tannins. If there are some crystals of triterpenoids present in the filtrate, this is not a problem. Other slightly polar organic solvents like ethanol or dimethyl carbonate can be used.Distillation and Crystal Formation

[0078] The filtrate containing triterpenoids (i.e. , the betulin, betulinic acid, and lupeol) and any high molecular weight tannins is then distilled until it is reduced to about 1 / 2022263.00006CAMR H712WO - PCT Application - FINAL42363573 v2(one twentieth) to about 1 / 4 (one quarter) of its original volume. This mixture is then allowed to cool, and as it cools, the triterpenoids form crystals (in this case betulin, betulinic acid, and lupeol crystals). After being cooled to ambient temperature (e.g., 20°C-30°C), there will be very light beige crystals, which are the triterpenoid crystals, and a dark brown liquor, which contains any high molecular weight tannins dissolved in acetone. The crystals are then filtered, for example, with a 10 micron to 20 micron filter, to yield a light beige to off-white powder.

[0079] The resulting betulin powder is dried and can be stored for years until used. This powder can then be added to oil or wax to form the triterpenoid composition.Alternatively, the oil or wax could have been added during the distillation stage, which results in betulin crystals dispersed in the oil or wax. This process is best suited for when only a small amount of oil or wax is wanted (0.01 % to 1 %) to simply coat the crystalline particles. In such a case, the betulin powder cannot be further cleaned of tannins; consequently, a more nonpolar solvent, like dimethyl carbonate, which is not as good a solvent for tannins, is best used as the extracting solvent.Adding Oil or l / l / ax Carrier

[0080] The filtered triterpenoid crystals are then added to a liquid oil or wax, or a solid oil or wax, to form a triterpenoid composition. The liquid oil can be, for example, almond oil. The solid oil or wax can be, for example, shea butter or beeswax. The triterpenoid composition can then be milled to as fine a particle size as desired, but no smaller than the wavelength of UV light. The milled crystals are no smaller than about 400nm, and preferably are at least 800nm in size.

[0081] The concentration of the triterpenoids is at least 10% by weight of the initial composition in order for the oil / wax mixture to have the appropriate thixotropy in the mill. After the milled material has cooled to room temperature (milling will cause the material to heat), the resulting material will be a powder, paste, or thick oil lotion, depending how much carrier oil or wax was used. When the crystal to oil ratio is 1 :1 or lower, the composition is generally a liquid oil. When the ratio is 7:3 to 1:1, the composition is generally a paste, and when the ratio is higher than 7:3, the composition is a powder. It 22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2is important to note that the high surface area of the crystals thickens the oil by creating a thixotrope. This is beneficial in cosmetics so the oil composition is not too thin, but it can still be applied easily.Alternative Extraction Methods

[0082] The chemical extraction is described above with respect to the bark sitting in the extraction solvent for a day or more; however, the extraction can be performed more quickly by a simple reflux extraction. In fact, the chemical extraction can be any extraction method known to one of ordinary skill in the art that extracts the triterpenoid active ingredients from the white birch tree bark while minimizing the extraction of tannins. For example, the chemical extraction can be Soxhlet extraction, steam distillation, supercritical fluid extraction, cold-press extraction, percolation, enzyme- assisted extraction, or any combination thereof. The chemical extraction proceeds in a temperature range and a pressure range that are each a function of the extraction solvent and the extraction method. For example, the chemical extraction can include refluxing dimethyl carbonate, in which case the temperature can be approximately 90°C, and the pressure can be in the range of approximately 1 atmosphere (atm). The temperature range and the pressure range can each be decided as would be by one of ordinary skill in the art.

[0083] The extraction solution (i.e. , the filtrate noted above) is distilled according to any distillation method known to one of ordinary skill in the art. Examples of appropriate distillation methods include simple distillation, fractional distillation, steam distillation, vacuum distillation, azeotropic distillation, batch distillation, or any combination thereof. Distillation occurs at temperatures and pressures that are a function of the extraction solvent and the distillation method. For example, if the solvent is dimethyl carbonate, the mixture can be distilled at a temperature of 90-100°C and a pressure of 0.95-1.05 atm.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2Tannin Removal

[0084] If the resulting betulin precipitate is thought to contain an undesirably high amount of tannins, these tannins can be removed by washing the betulin precipitate with water that is alkaline and has a pH of 7-1 . The alkalinity of the water can be created by dissolving an alkaline salt such as sodium hydroxide, calcium hydroxide, or a Lewis Base such as triethyl amine, in the water. The alkaline salts or Lewis Bases in the water will increase the solubility of the tannins into the water, enabling the tannins to be washed away from the betulin precipitate (which will not dissolve in the alkaline water).Post-Treatment and Milling

[0085] The betulin crystal powder, or dispersion of triterpenoid crystals in the carrier medium, can be further treated if necessary to bring the triterpenoid composition to a form that is suitable for topical applications. For example, the mixture can be milled to reduce the size of the triterpenoid crystals and / or to change the shape of the triterpenoid crystals. The crystals can be milled as small as 400nm in diameter and will still be effective for scattering UV light. If the crystals are smaller than 400nm in diameter, they will not scatter UV light. Milling can occur according to any method known to one of ordinary skill in the art. For example, milling can include ball milling, planetary milling, jet milling, colloid milling, sonication, or any combination thereof. As the triterpenoid crystals have high melting points, milling can be performed at temperatures as high as 250°C without risk of melting the active ingredients.Coating Betulin Crystals with Low Refractive Index Materials

[0086] To coat the betulin crystals with low Rl materials, including but not limited to coconut oil, almond oil, isopropyl laurate, butyl laurate, polydimethyl siloxane, or quassin, dissolve the uncoated betulin crystals in twice the weight of dimethyl carbonate. So, for every 100g of betulin crystals, add 200g of dimethyl carbonate. For every 100g of betulin crystals, add 50g or more of the low Rl material. If a powder is wanted, do not add more than the equivalent weight of the low Rl material; in other words, no more than 100g of low Rl material for 100g of betulin crystals. Reflux the22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2resulting material until the betulin crystals have dissolved. If they do not completely dissolve, add more dimethyl carbonate and continue to reflux until they dissolve and the solution becomes clear. Distill the dimethyl carbonate from the solution until the solution temperature reaches 110°C.EXAMPLESExample 1: Extracting Pure Betulin Crystals

[0087] Betulin crystals consisting primarily of betulin with betulinic acid and lupeol are made by putting 1 kg of the outer bark of Betula Papyrifera (paper birch) in an extractor underneath which holds a pot of 10kg of dimethyl carbonate. The Betula Papyrifera should be shredded into no larger than 1" square pieces in order to allow easy extraction. Dimethyl carbonate is an ideal solvent because it has a boiling point of 90°C, which is high enough so its vapor can dissolve and extract the triterpenoids, but is low enough to easily remove after extraction. The triterpenoids are readily soluble in it at 90°C but crystallize out at room temperature. Tannins and other phenolics are not soluble in it at 90°C, so the extracted liquor is substantially void of these chromophores. Preferably, the resulting crystals will be of a high purity, having less than 1% tannins or other phenolics.

[0088] The dimethyl carbonate is boiled for 12 hours. The dimethyl carbonate should be returned into the pot and the evaporation of dimethyl carbonate should be limited as much as possible. Ideally, a reflux condenser should be installed above the birch bark. After 12 hours, the heat should be turned off and the solution allowed to cool. Once the dimethyl carbonate is at room temperature, the extracted bark can be removed and new bark can be added. The dimethyl carbonate should be heated again and the process can be repeated. Each 1 kg of birch bark will lead to 200-300g of birch crystals.

[0089] The process of extraction, cooling, replacing the spent birch bark, and replacing with new birch bark can be repeated up to 10 times using the same pot of dimethyl carbonate. The pot of dimethyl carbonate will be orange brown, though this is not due to contamination with tannins or phenolics. The dimethyl carbonate is distilled away using22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2a distillation head and the temperature of the solution is monitored. When the dimethyl carbonate is distilling, the solution temperature is 90°C; however, as the betulin solution becomes more concentrated, the temperature will begin to rise. When it reaches 95°C, the distillation should be stopped. 90% of the dimethyl carbonate should have been removed and this can be reused for further distillations. The betulin liquor is allowed to cool; as the solution cools, crystals will begin to grow. When the temperature has reached 23°C, the betulin crystals can be filtered. This will result in pure betulin crystals that can be stored.Example 2: Preparation of Triterpenoid Composition and SPF Testing

[0090] A 20% by weight triterpenoid composition (triterpenoid crystals in almond oil) was prepared as described above. 1 gram of the 20% by weight triterpenoid composition was added to a water-based lotion such as ordinarily used as a topical support for a ZnO-based sunblock, resulting in a water-based lotion containing 0.2 grams of the triterpenoid crystals. The result was a betulin-based sunblock lotion which has emollient properties. The betulin-based sunblock lotion was then measured for its sun-protection factor (SPF) and was surprisingly found to have an SPF of 50. This was then compared to a sample of a water-based sunblock comprising 1 gram of ZnO. The ZnO sunblock was found to only have an SPF of 30.

[0091] In the reflection spectrum, it is shown that UV light (which is less than 400nm) is reflected, whereas visible light (which corresponds to 400nm-800nm) is not reflected in the film. Thus, it was found that the betulin-based sunblock lotion had the advantage of more appealing visual transparency and a surprisingly higher SPF rating than the zinc oxide-based sunblock lotion.Example 3: In-Vitro SPF Testing

[0092] In-vitro SPF testing was performed on three samples: a control sample consisting solely of almond oil, a 10% by weight triterpenoid composition as described above, and a 20% by weight triterpenoid composition as described above. The triterpenoid crystals in the triterpenoid compositions were about 95% betulin crystals with the remainder22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2being betulinic acid or lupeol crystals. Each sample was loaded onto its own polymethyl methacrylate (PMMA) helioplate. Each helioplate had a roughness averaging 6 microns. Each sample was applied onto its respective helioplate at a density of 1.2 mg / cm2. The process of applying each sample took 30 seconds and was done using a powder-free finger cot. Each plate was then dried for exactly 15 minutes. SPF values were then measured using a laboratory transmittance analyzer at ten different locations on each plate.

[0093] Results indicate absorbance of ultraviolet light with 10% and 20% Betulin samples.

[0094] In these tests, an SPF scale of 1 to 20 is considered standard; thus, an in-vitro test SPF of 1 corresponds generally to an in-vivo sunblock SPF of 20. Thus, in the control (Plate 1 ), the oil with no betulin was found to have an SPF of 19 (19 / 20=0.95). Thus, the measured SPFs of the 10% and 20% betulin compositions of 1.61 and 2.91, respectively, correspond to SPFs of 32.2 (32.2 / 20 = 1.61) and 58.2 (58.2 / 20=2.91). Thus, use of betulin, even at a low loading of 10% by weight, provided an unexpectedly high SPF, meaning that even at low triterpenoid crystal loadings, the sunblock composition will have a high SPF.

[0095] In-vitro SPF values do not correlate exactly to in-vivo SPF values (such as those measured from finalized commercial sunblock formulations applied to a user's skin) for many reasons. However, in-vitro SPF is a useful screening tool for comparing the relative performance of one sunscreen to another prior to in-vivo SPF study evaluation. Furthermore, the application dose for the in-vitro test described above is lower than the in-vivo application dose due to the differences between PMMA plates and human skin.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2Even considering the foregoing, the tests still show that the triterpenoid-based sunscreen composition produced an unexpectedly high SPF. \Example 4: Reflectivity and Absorbance Testing

[0096] Betulin, betulinic acid and lupeol all have strong UV absorbances at 210nm, but also smaller absorbances at 275nm that carries out to 350nm. It is believed that these absorbances may cause the refractive index to increase dramatically in the UVB and UVA range. This would make the reflectivity of almond oil coated betulin crystals go up dramatically in the UV wavelength range. For example, if the refractive index of betulin crystals is even just 1.7 at 325nm (UVB light) the % reflection of normal incident light at that wavelength is 2.3%. High energy light is more sensitive to the angle of incidence; therefore, the reflectance of betulin crystals might be dramatically higher for UVB and UVA light than visible. The UV reflectivity of almond oil coated betulin crystals was therefore tested, with results shown in FIG. 8.

[0097] FIG. 8 shows the reflection of light from 290nm to 400nm with almond oil containing betulin crystals. The control (bottom) trace is pure almond oil, the middle trace is almond oil with a 10% loading of betulin crystals, and the top trace is almond oil with a 20% loading of betulin crystals. The pure almond oil has absolutely no reflection until 300nm. However, the samples containing betulin are nearly transparent at 400nm, but there is a strong reflection of light that steadily increases throughout the UVA1 range of 340nm - 400nm and peaks at UVA2 of 315 - 340nm. The reflection is very strong throughout the UVB range of 290nm - 315nm.

[0098] FIG. 8 shows that although the betulin crystals coated with almond oil reflect much less 400nm light than they do 325nm light, they still reflect a lot more light at 400nm than does pure almond oil . This gradual decrease in reflectivity seen in the violet range (380nm - 400nm) continues throughout the visible light range and is the reason for the tan color of the coated betulin crystals.

[0099] Key to the technology composition is the fact that the betulin crystals are very crystalline, very tenacious, and do not get destroyed when coated with materials or22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2dispersed in oil based or water based lotions. In summary, betulin crystals are essential for this patent because they have a combination of the following properties:1. A high refractive index which averages about 1.51 in the visible range of light.2. A refractive index that increases from 1.49 in the blue to 1.52 in the red.3. A refractive index that goes up dramatically through the UVA and UVB range of light.4. Substantially optically transparent from 290nm to 750nm.5. A high crystallinity and an ability to form needlelike crystals with many surfaces.6. A high melting point (256°C) and a high boiling point (285°C).7. A strong crystalline lattice that makes it poorly soluble in organic solvents or water.8. The strong crystalline structure along with high melting point and low solubility makes it difficult to amorphized in any solvent or material.

[0100] The description herein is merely exemplary in nature and, thus, variations that do not depart from the gist of that which is described are intended to be within the scope of the appended claims. Moreover, although the foregoing descriptions and the associated drawings describe example embodiments in the context of certain example combinations of elements and / or functions, it should be appreciated that different combinations of elements and / or functions can be provided by alternative embodiments without departing from the scope of the claims. Such variations and alternative combinations of elements and / or functions are not to be regarded as a departure from the spirit and scope of the teachings.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

Claims

What is claimed is:

1. A triterpenoid composition comprising crystals of triterpenoids or triterpenoid salts dispersed in, or coated with, a medium comprised of an oil or wax.

2. The triterpenoid composition of Claim 1, wherein the triterpenoids are selected from the group consisting of betulin, betulinic acid, lupeol, salts thereof, and combinations thereof.

3. The triterpenoid composition of Claim 2, wherein the betulin and betulinic acid are present in a ratio of 1.0:99.0 to 99.0: 1.0.

4. The triterpenoid composition of any of Claims 2-3, wherein the betulin and lupeol are present in a ratio of 0.5:98.5 to 98.5:0.5.

5. The triterpenoid composition of any of Claims 1-4, wherein the triterpenoid crystals have an average size of at least 400nm, and preferably an average size of about 800nm to about 10 microns.

6. The triterpenoid composition of any of Claims 1-5, wherein the oil is selected from the group consisting of almond oil, coconut oil, grapeseed oil, avocado oil, and combinations thereof.

7. The triterpenoid composition of any of Claims 1-6, wherein the composition is generally or substantially transparent to visible light.

8. The triterpenoid composition of any of Claims 1-7, wherein the composition is substantially opaque to UV-A light and UV-B light, and preferably generally transparent to red light.

9. The triterpenoid composition of any of Claims 1-8, wherein the crystals of the triterpenoids comprise about 0.5% to about 95.5% by weight of the composition, and preferably about 3% to about 20% by weight.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v210. The triterpenoid composition of any of Claims 1-9, wherein the crystals of triterpenoids or triterpenoid salts have a refractive index of about 1.45 to about 1.55 and the medium has a refractive index of about 1.40 to about 1.49.

11. A triterpenoid composition comprising light reflecting crystals dispersed in, or coated with, a medium comprised of an oil or wax, wherein the crystals and the medium have refractive indices within about 10% of each other, and wherein the triterpenoid composition is substantially visibly transparent.

12. The triterpenoid composition of Claim 11 , wherein the crystals have a refractive index of about 1.45 to about 1.55 and the medium has a refractive index of about 1.40 to about 1.49, and wherein the crystals are crystals of triterpenoids or triterpenoid salts.

13. The triterpenoid composition of any of Claims 1-12, wherein the triterpenoid composition is a sunblock composition.

14. The triterpenoid composition of any of Claims 1-12, wherein the triterpenoid composition is a skin emollient.

15. A mixture of triterpenoid crystals suitable for use in a sunblock composition, said triterpenoids being chosen from the group consisting of betulin, betulinic acid, lupeol, betulin derivatives, salts thereof, and combinations thereof; said crystals having less than 1% tannins or other phenolics; said crystals being produced by extracting the terpenoids from the outer bark of any of the genus Betula with dimethyl carbonate or diethyl carbonate, and condensing the solvents to yield the betulin crystals; preferably, wherein the bark comes from Betula Alba (White Birch), Betula Pendula (Silver Birch), Betula Neoalaskana (Alaskan Birch), or Betula Papyrifera (Paper Birch).

16. A triterpenoid crystal composition comprising triterpenoid crystals coated with, or immersed in, a medium such as almond oil, coconut oil, grapeseed oil, isopropyl laurate, or quassin that is transparent to UVA, UVB, and visible light and has no chromophoric functionality absorbing wavelengths of light between 290nm and 750nm but has a refractive index (Rl) of 1.45-1.47, for use as a block for skin-damaging UVA and UVB light while being transparent when applied to skin, wherein the triterpenoid is 22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2chosen from the group consisting of betulin, betulinic acid, lupeol, betulin derivatives, salts thereof, and combinations thereof.

17. A method of preparation for the triterpenoid composition of any of Claims 1-16, wherein the method comprises the steps of:extracting triterpenoids from birch bark into an extraction solvent to form a solvent solution comprised of triterpenoids in the extraction solvent; and either(a1) adding an oil or wax carrier to the extraction solvent, resulting in a carrier / solvent solution mixture;(a2) distilling the carrier / solvent solution mixture to evaporate the extraction solvent, to form a mixture of triterpenoids in the carrier; and(a3) cooling the mixture of triterpenoids in carrier, enabling the triterpenoids to form triterpenoid crystals in the carrier; or(b1) distilling the solvent from the extraction solvent until a powder is formed; and(b2) adding an oil or wax carrier to the powdered triterpenoid powder and mixing or milling the oil to coat all of the crystalline particles.

18. The method of Claim 17, wherein step (b2) is performed shortly after step (b1) is completed, or wherein, after step (b1 ) is completed, the powder is stored, and step (b2) is performed at a time remote from step (b1).

19. The method of any of Claims 17-18, further comprising a step of milling the triterpenoid crystals after the mixture has been distilled.

20. The method of any of Claims 17-19, wherein the step of extracting the triterpenoids from the birch bark is performed by soaking the birch bark in the extraction solvent or by refluxing the extraction solvent through the birch bark.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v221. The method of Claim 20, wherein the step of extracting the triterpenoids from the birch bark is performed until white matter is substantially no longer visible in the birch bark.

22. The method of any of Claims 17-21 , wherein the triterpenoids are selected from the group consisting of betulin, betulinic acid, lupeol, salts thereof, and combinations thereof.

23. The method of any of Claims 17-22, wherein the extraction solvent is dimethyl carbonate or acetone.

24. The method of any of Claims 17-23, wherein the oil is almond oil.

25. A method of coating betulin crystals with coating media having a low refractive index, said method comprising dispersing the betulin crystals and the coating media in a solvent, such as dimethyl carbonate, in which the betulin crystals are less soluble than the coating material, and subsequently evaporating the solvent, wherein upon evaporation of the solvent, the betulin crystals crystallize first and the coating media coats the outside of the crystals.

26. A method of coating triterpenoid crystals with a coating media, the triterpenoid being chosen from the group consisting of betulin, betulinic acid, lupeol, betulin derivatives, salts thereof, and combinations thereof; the method comprising extracting the triterpenoid from white birch bark using dimethyl carbonate or ethyl carbonate and subsequently evaporating the dimethyl carbonate or ethyl carbonate to yield coated crystals.22263.00006CAMR H712WO - PCT Application - FINAL42363573 v2

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