CA2188166C - Composite uv sunblock compositions - Google Patents

Abstract

The invention encompasses topical sunblock formulae for shielding skin from ultraviolet radiation, and a composite sunblocking component thereof. The sunblocking component of the formula includes an effective amount of a plurality of particles having diameters in the range of about 0.01 - 100 microns, each particle including a matrix and a UV-attenuating compound incorporated into the matrix.
The composite sunblocking component may include a particle that is colored or transparent, depending upon the matrix, UV-attenuating compound and the particle size. The sunblocking component is dispersible in water and thus in water-based dermatological carriers. The formula includes these particles dispersed within a dermatologically acceptable liquid carrier in at least an amount sufficient to shield substantially all of the skin over which the formula is applied from hazardous effects of ultraviolet radiation.

Description

WO95128912 (~ A 2 18 ~ 16 6 r~ x~ ol31~

rt~MPOSITE W SUNBI,OCK coMPOSITIONS
FTT~T n OF T~ INVE21TION
The present invention relates generally to particulate materials adapted for use as sunblocking agents and more particularly to the use of these materials in tran-~a~ellL oi colored, cosmetically acceptable W sunscreen products, as well as in; uve:d cosmetic formulations having an increased ability to protect the user rrom W radiation.
BA~ u~ ~ OF THE INVENTION
One portion of the solar ~ LL u..l comprises wavelengths of ele.:LL i c energy which range between about 290 and 3, 000 ~- s (nm) This range may be divided into different regions, namely: (1) the ultraviolet region (290-400 nm), (2) the visible region (400-760 nm) and (3) the near-infrared region (>760 nm). The ultraviolet region has, e~JVt:L~ been arbitrarily divided into three bands, referred to as the WA, WB and WC bands.
The WB band extends from 290 to 320 nm. It is the principal cause of the sunburn reaction and it is also the most effective in stimulating the tanning reaction in the 2 81 66 r~ E12 skin. WC radiation (200-290 nm) from the sun does not reach the surface of the earth, although one can encounter radiation in this range from artificial sources such as germicidal lamps and high and low pLes~uL~ mercury arc lamps.
For purposes of the present invention, however, protection against WC radiation is generally not a major concern, i.e., in ~ LL C~ L to the dangers posed by WA and WB radiation .
The WA band, which extends from 320-400 nm, can also cause the tanning reaction. WA radiation can also cause sunburns, but its capacity to do so is less than that of WB radiation.
The amount of WA radiation e~o~uL~ however, is increasing. This is due to the fact that most sunscreens effectively block only W3 radiation. As stated above, WB
radiation is more capable than WA radiation of causing the tanning and burning reactions. Therefore, if one is using a r u~ -- that blocks WB radiation he/she will tend to stay in the sun for an extended period of time because the immediate effects of the sun tan/burn are not evident. The problem is that WA is still ~el.~=LLi-ting the skin and although it is not causing any immediately obvious effects, it is causing long term damage. In recent years, it has been well ~1- Led that WA radiation, like WB radiation, i8 harmful to the 6kin. In fact, current data reveal that solar radiation containing these wavelengths (A and B) is a contributing cause of skin cancer, which presently accounts for 30-40% of all new cancers each year. In the United States alone, 500,000 new cases of skin cancer will be W0 95128912 C Q.2 ~ 8 8 ~ 6 6 r~~ 12 .
reported this year and the number is P~artad to keep rising in the future. WA radiation has been shown to promote skin cancer by inhibiting enzymes that repair cells damaged by WB
radiation. WA radiation also pe~ L~tes more deeply into the skin than WB radiation and causes changes in blood vesDsels and ~IL- ~UL'2 aging of the skin, thus adding to the damage produced by UVB rays (see, e.g., Hurwitz, Sidney, "The Sun and Su..s~ ... ,. Protection 17a_ -tions ~or Children", Dermatol Surg. Oncol; 14:6(June 1988) p. 657). The goal of any sunscreen should thus be to protect the user from both WA and WB radiation with a minimum of side effects. This end has not been adequately achieved with the use of prefiently available DUII~ ll products.
Topical ~u~s~ ell products can be grouped into two broad categories, i.e., organic and inorganic tphysical) DUIlS~,L~el~S .
Commercially available DUI15~ 11 products contain from about 3 to about 26% of one or more W absorbing rhamicAl~:.
When applied to the surface of the skin as a thin film, i.e., about 10-15 ~Lm in ~h~rl~nP~s, these rhom;rAl~ act as a filter to tiim;nlP:h the penetration of W radiation to the cells of the epidermis. These sunscreens are typically applied in a cream, oil, lotion, alcohol or gel vehicle and they are usually colorless because they do not contain any visible light-absorbing chemicals. The most widely used organic-based sunscreens contain, for exa_ple, para-Aminnhan7oic acid (PABA), PABA esters (glyceryl PABA), amyl li- yl PABA and WO95/28912 ` ~ 8 ~ ~6 ~ C:E12 .

octyl~li~ yl PABA), hPn7orhPnnnPc (oxybenzone and l i ct~l~an~ P) ~ cinnamates (octylmethoxy cinnamate and cinoxate), salicylates (h~ L11yl salicylate), anthranilates such J~s menthyl anthranilate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, 2-phenyl benzimidazole-5-sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, 2-ethyl-2-cyano-3, 3 ' -diphenyl acrylate. To date, more than twenty-one such rhPm;c~lc have been d}~uLuv~d by the United States Foo~ and Drug Administration as "safe and effective"
agents in protecting skin against sunburn (see, e.g., Pathak, Madhu, "Sun6creens: Topical and Systemic Approaches for Protection of Human Skin Against Harmful Effects of Solar Radiation", Continuing ~edical Education Series, J. Am. Acad.
Dermat., 7:3 (September 1982) p. 285,291).
Questions have recently been raised, however, by the medical profession as to whether the organic l hPmic:~l _ ^ntS of these DUllSU' ~ells are indeed inert and further, whether repeated use of such ~-U~IS~ L t ~..s can result in significant trAnC~l~rr~l absorption of these chemicals.
Because rh~mici~l ,4lls~;L~ccl.5 are applied topically in relatively high UU.I- ~,lLL ltions (i.e., up to 26%), contact and photocontact sensitization can occur, as well as llylJeLl ~llsitiVity, i.e., photoallergic r~ innC (see DLI, :Jle et al., "Su-.s.:L~elling Agent Intolerance: Contact and Photocontact Sensitization and Contact Urticania", J. Am.
Acad. Dermatol., 1990:22, p. 1068).

WO95/28912 r 9 ~ 2 1 88 1 66 r~~ 12 i ~ .
Physical or inorganic ~ulls~Leel.s, on the other hand, comprise particles of a relatively physiologically inert 8-~nhlo~ 1~, i.e., T~V-absorbing, _ _ typically s~ p~n~lD~
in a cream or lotion. Naterials r.e:.lu~l-Lly utilized for this purpose include kaolin, talc and two metal oxides, i.e., titanium dioYide and zinc oxide. The latter two _ are not associated with the inf lammatory reactions noted above .
The physical sunscreen products are, however, typically messy and occlusive. Il~ ve:L, they additionally form a visible, colored (e.g., white) layer on the surface of the skin which is cosmetically unacceptable to many who are in need of sunscreen protection. This causes many such individuals to forego the use of these ~Ludu. Ls. The color of these compositions is attributable to the optical properties of the particles from which these materials are formed. These properties are at least partially flPpC r~ t upon the size of these particles, which typically have a ' ~r of > 250 nm (i.e., 0.25 microns).
In addition, presently available physical ~ull,.;L~ens are not easily washed off of the user's body. Instead, the base typically "melts" off with the heat of the sun, thus incidentally staininq or otherwise discoloring the user's clothing. rl~ v~l, because they are applied as relatively thick films, i.e., greater than 10 ,um, use of these products may also promote undesirable skin conditions, including W095/28912 ; ~ C A2 1 88~ 66 ~ ot~2 miliaria, a skin disease caused by an inflammation of the ~weat glands, and folliculitis, an inflammation of the hair follicle. As such, these physical sunscreen products are deemed - 1 r:~ l l y unacceptable by a large class of image ronri ~llfl persons, which primarily includes young people.
Unfortunately, this same group is the exact population that needs solar protection the most. It has been stated that proper use of .,u..s~, ~el.s prior to the age of 18 would prevent 80~ of skin cancers (see, e.g., Taylor et al., "Photoaging/Photo~l~r~~e and Photoprotection", 22 J.Am. Acad.
Dermatol., ~ (l990).
In one variant of the "typical" prior art physical 5llnhl0rl~u described above, certain commercial sunscreen products containing titanium dioxide are made with what is known as "micronized" or "large surface area" particles of the metal oxide. These particles have a diameter an order of magnitude smaller (i.e., measuring about O.Ol - O.l,u) than the "~:tandard" pigment-grade sized particles (measuring about 0. 25 ,U) described above.
Greater public awelr~ --ess of the harmful effects of elA~JOr~U. d. to excessive solar radiation has therefore resulted in an increased use of sunscreen products by the public, coupled with a call for i .,v-:d -u-ls~;L~e-- materials free of the d~ a~ h~i described above by those whose livelihood and/or leisure activities cause them to be exposed to any substantial amounts of solar radiation.

Ch2~88,66 W0 95128912 ; , ~ 12 It is thus an object of the invention to provide new, ; _ vv~d i~Ally acceptable physical sunblock _aterial6 capable of attenuating a greater degree of ultraviolet radiation sDo as to prevent the user's skin from being damaged by ~ vDuL-~ to these solar rays.
It i8 a ~urther object of the invention to provide sDunscreen ~Lvdu~;~D ut;l1~in~ sunblocks of the type described above which are capable of effectively attenuating WA and UVB radiation while ref~;n;n~ a substantially visibly clear or a having colored appearance, if desired, upon the surface of the skin.
It is still further object of the invention to provide physical sllnhlork~: which do not cause adver8e rh~m;
reactions upon the skin of the user.
It is another object of the invention to provide a physical sllnhl orl~ ~ which does not interact with other formulation ingredients.
It is another object of the invention to provide a variety of 1 vv~d cos_etic formulations containing the particulate s-~nhlork materials described herein which offer an ~-nh~nr~-d degree of solar protection to the user.
It is a further object of the invention to provide an inherently non-water-soluble organic sunscreen L that is not restricted to use in an oil phase of a ~ull8vL-~e 1 ~ion .
Yet another object of the invention is to provide a ~u.,~ .~en ~ ~ that is m;~c;hle with a water-based WO 9S/28912 C i~ 2 1 8 8 1 6 6 r~ Q I '~

sunscreen; for example, to adapt previously oil-based Du........... s~.L-~en s for use in a water-based sunscreen.
Another object of the invention is to adapt a sunscreen ~ to make it water-dispersible.
Yet another object of the invention i8 to adapt a DUIIS~:L~ to min;m; 7e undesirable chemical reactions between the ~ and other active ingredients in the sunscreen formula.
A further object of the invention is to provide for facile ~L~paLation of a sunscreen ~ t by avoiding the use of undesirable rhPm;cAlc, e.g., solvents, in the manufacture process.
Another obj ect of the invention is to increase the efficacy o~ the ..ul-6- l- en; that is, to confer a higher sun protection factor than is available from conventional ens using approximately the same volume.
Yet another object of the invention i8 to provide a particle having an ~nrArs~lAti~g ~ that promotes film formation, thereby causing the particle to adhere to the skin and confer a waterproof quality to the sunscreen.
STTMM~RY OF THE INVENTION
A f ir~t l~mho~ of the invention is directed to the formation of sunscreen products comprising a plurality of small cArs~ c or particles, the particles having diameters in the range of approximately O.Ol to l00 microns, and preferably 0.0l to 50 or O.Ol to 20 microns, containing one _ ~

~W095t2891Z i `~ A2~8166 r~ ~
g or more W-attenuating (i.e., W-absorbing or -reflecting) '-. Preferably, the capsule confers a visibly clear quality to the sunscreen as applied to the skin; however, color additives may be added to the particles to confer a color quality to the sunscreen as applied to the skin.
Preferably, the capsule is spherical. Preferably, the average diameter of the particles in a plurality of particles is 0.5 - 50, and most preferably 1 - 10 microns.
Thus, the invention features a component of a sunblock formula comprising a plurality of particles, having diameters in the range of about 0 . 01 - 100 microns, formed from a matrix and at least one W-attenuating ' inCVLyVL~lted into the matrix, the particles being dispersible within a substantially transparent dermatologically acceptable liquid carrier.
A aull uL-~en L of the invention is distinguishable over prior art sunscreen ~ Ls in several respects. For example, aUIlaVL~ l particles of the invention are dispersible in water and thus in water-based dermatological carriers, even particles containing W-attenuating _ --ts that are inherently difficult to disperse by virtue of certain surface properties. For example, the particles may be c~ of an oil-soluble material that is not water-soluble but for the ~nr~r5ll1Ating matrix; i.e., the oil-solubilizing properties are masked by the ~nrArclllAting matrix, rendering the ~nrArs~lAted materia dispersible in water.

W095/28912 ,, ` ~ r A 2 1 8 8 1 6 6 r~ c 1_~7 The .iu..su.~ nt also is disting~ hAhle over prior art DU115~L ._n s in that it is ~ ed according to a manufacture process that does not require the use of an int~ - ; Ate organic solvent, and thus both the manufacture process and the Dul-s~ ell product are completely free of such solvents. That is, a water-dispersible nu1l8~Lcc~ is provided according to the invention without such highly toxic and thus undesirable chemicals.
The level of organic solvents present in the water-dispersible sunscreen ts described herein are substantially lower than those found in the prior art ~UII~L~,L~ 5 that are made using solvent-extraction methods of manufacture, where toxicity is a concern.
Applicants' PnrArg~ ted DUllDULt~ 5 have ~Yree~lin~ly low, i.e., undetectable levels, of organic solvents and are therefore referred to in the present specification as "solvent-free".
Thus, an ; ~llll. advantage of the ~nrArSI~ 1 ~ted ~iUI~5~:L~ 5 of the invention is found in their safety and ease of manufacture. The ~UI~5~;Ll~
achieved via solvent-free methods of manufacture are also le6s toxic than solvent-synthesized ~8, an important çt~n~ ration for agents applied to the skin. This solvent-free material is thus suitable for application to human skin since the solvent content is present at undetectable levels and thus is not likely to cause dangerous effects in humans.

~WO9s/289l2 ; ;'~ ~h2188-166 r~ c~12 A preferred ~n~Arsll~nting matrix useful according to the invention comprises wax. As used herein, "wax" refers to a natural or synthetic material having the following characteristics; i.e., it is essentially non-water soluble (i.e., < 5%); it has a melting point preferably below 100 degrees but not above 200 degrees Centigrade; and it has a viscosity of less than 500 cp. at a tr c.Lu~ less than 100 degrees Centigrade. The invention Pn ----c the use of an ~-nr:-rSlll Ating material that does not possess these characteristics alone but is combinable with another material to produce a mixture having all of these characteristics.
Waxes include, but are not limited to, natural and sy-nthetic waxes that contain mixtures of alkyl wax esters, resins, and other ve~et~hle matter ~ ~s; clay-treated mi.i~ ;Ly~dlline waxes; nY~ yd~o~ a- waxes; natural and synthetic beeswax, auto-oxidized beeswax, c~n~ ;l;a, carnauba, and synthetic waxes ~ . ~ared by esterif ication of natural plant-derived fatty acids and alcohols; various grades of paraffin waxes; and natural and synthetic oils.
Other preferred matrices include but are not limited to materials that are ~nr~rs~ tors according to a solvent-free process , e. g ., polymeric materials such as alkylated vinyl pyrrolidone polymers; long chain alcohols; long chain carboxylic acids; propylene glycol ester of fatty acids;
ethene homopolymers; various grades of polymerized alkenes and alpha alkenes with molecular weights greater than 100 W095128912 i ` C A 21 8 ~ 1 6 6 rC~ 2 g/mole; ethylene-acrylic acid copolymers; ethylene-vinyl acetate copolymers; and lipid and protein-derivatives.
These pLe r-:L ed matrices have the additional advantage of being {n~-Yr-~nRive and relatively non-toxic, as they are commonly-used cosmetic ingredients.
Optimally, the W-attenuating - _ ' is ~nrArCI-l Ated within the matrix particle such that, upon admixture of the W-a~t.luelting ~ rn A~ ej l Ated particles with a :iUIlS. r e:~:ll emulsion, the W-attenuating _ _ ' does not substantially contact the ~uLLuu.lding emulsion or the skin.
Alternatively, the W-attenuating, a may be combined with the matrix in formation of the particle such that the _ ,_ a is substantially evenly-distributed L~1LUU~11UUL the matrix.
Thus, the invention also ;nrl~ c a ~U~ID-L~ell formula comprising two or more W-attenuating ~ _ '-, each ' individually PnrArs~lAted in the matrix to form a first plurality of particles comprising a first ~nr~Arc~lAted W-attenuating ' and a second plurality of particles comprising a second l~nrArslll Ated W-attenuating _ ', etc. When formulating a DullDur~en formula, any given ratio of the first or second plurality of particles may be _ ' ;ned in the sunscreen formula to provide an effective amount of sunblock .
Alternatively, the invention ~n~ ,~ccPs first and ~;econd W-attenuating aA that are together ~-nrArSIIlAted in the matrix. The first and second W-:
w0 95128912 C ~i 2 ~ ~ 8 ~ 6 6 P~l/L8~ 12 attenuating ~ e may be organic or inorganic sunscreen - agents. Organic agents include but are not limited to nhPm;CAl Iju~ Lo~ 5 such as ~Pn7o~hPnnnpR' PABA and PABA
derivatives, cinnamates, salicylates, anthranilates such as menthyl anthranilate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, 2-phenyl bPn71m;~l~70le-5-sulfonic acid, digalloyl trioleate, 3-t4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, 2-ethyl-2-cyano-3, 3 ' -diphenyl acrylate . Inorganic agents include but are not limited to kaolin, talc, titanium dioxide, and zinc oxide .
Of course, it is to be understood that the invention ~- _ CCPA a ~,u~s~ formula comprising particles nnnt~in;n~ not only first and second W-attenuating '-, but also, if desired, third, fourth and fifth, etc. W-attenuating '-, whether the multiple W-attenuating '- be individually Pn~-~rclllated or Pnr; r81~ ted in combinations.
The invention thus also provides a method of preparing the sunscreen ~ L described above, comprising subjecting the matrix and the W-attenuating ' to a solvent-free process to produce a solvent-free plurality of particles comprising the matrix and the W-attenuating Additional advantages of the invention include providing an Pnr~rclll~ted organic Lu--~ en L that, by virtue of its inert encapsulating exterior is not restricted to use WO 95/28912 1 ~ll LJ... _.'0 :_12 - ` CA21~8166 in the oil phase of a sunscreen emulsion. Thus, the ~-ncAr ~lAted ciu~S- Leen ~ L will be dispersible in a water-based ~.ull6.Leen, if desired. Inherently oil-soluble ~UII _L~ may thus be adapted for use in a water-based ~ullA-~eell, and thus may be rendered water-dispersible.
In addition, a toxic ~u..su-èel- may be rendered less toxic or non-toxic via ~nr~r~ Ation accord~ ng to the invention. Also, the use of encapsulated L5 will ~;n;m;7e the undesirable rh~ Al reactions between the -~ L and other active ingredients in the sunscreen formula. Thus, ambient conditions around the ~UI15~:Lèe~l L itself within the ~Ulli~;L~::ell formula may be controlled by the presence of the ~ncArslllAting substance, regardless of the activities of additional Ls in the ~UIl~uLeell formula. Another important advantage of the invention is that an ~nrArs~ ted :,u..~-;Lèen provides a higher ~un protection factor than an ~ lAted active sunscreen gent, when applied at the same cv...e--Ll~ltions.
In another aspect, the invention provides a process for preparing a - L of a sunscreen formula, comprising the steps of: (a) heating an ~-nrArslllAting matrix above its melting point at a t ~ULè in the range of 30 - 200 degrees Centigrade to form a liquified, i.e., molten, ~nrAr5-ll Ating matrix; (b) mixing a W attenuating ~ _ ' with the liquified ~nrArslllAting matrix; (c) emulsifying the mixture of step (b) with an aqueous medium comprising a surfactant, the aqueuuc. ~ -ium being at a t~ CltUL_ in the wo95128912 CA218&166 i j ~ J,.,s/0l~12 range of 30~- 200 degrees Centigrade upon emulsification, such that the emulsion drop size is in the range of about 0.01 - 100 microns; and (d) cooling the: lcion to room t~ ~u~, wherein the particles formed therefrom have ~; teLD in the range of about 0.01 - 100 microns and comprise the matrix in combination with the W-attenuating ', the particles being solvent-free and dicpersible within a dermatologically acceptable carrier.
In preferred ~ Ls, the t~ ~ILUL~ range of steps (a) and (c), individually, is 30 - 100 degrees Centigrade;
the r-nr~rc~ ting matrix comprises a substance s~lect~d from the group consisting of: natural wax and synthetic wax; the natural waxes comprising a material c~l ect~l from the group consisting of alkyl wax esters, resins, and other vP~p~LAhlr~
matter L~; clay-treated mi.;Lo~.Ly~Lalline waxes;
nYir'i; 7e~1 hydrocarbon waxes; natural and synthetic beeswax, auto-nYi~i~o:l beeswax, ~An~ l;A, carnauba; the synthetic waxes comprising a material selected from the group consisting of synthetic waxes prepared by esterification of natural plant-derived fatty acids and alcohols; various grades of paraffin waxes.
In other pref erred : ' _ '; - L:~, the W-attenuating ' is an organic or inorganic W-attenuator; the inorganic W-attenuator is ~l c LL eated with a hydrophobic ~ d prior to mixing with the heated ~n~ ~rsl~lAting matrix; the organic sunscreen material is admixed with a 50ll-hil;~in~ agent prior to incuL~uL~ltion into the matrix iD

wo 95/28912 C ~ ~ ~ 8 8 6 6 -~ PCrluS95/04842 an amount suf f icient to reduce the potential of the W-Attenuator to L__Ly~llize in the particle form.
In a second: ' 'i L, the invention i5 directed to a ~UIl8~L~ll formulation comprising microfine particles of a zinc oxide s~ hlorl~ 5llcp~nd~d in a der~atologically suitable liquid carrier, preferably in the form of an emulsion. These micronized particles, as now p- ~ duce~ by applicant~ii, are formed using known techniques, such that the resultant particles have acceptable, i.e., reduced, levels of trace metals such as cadmium, arsenic, mercury, lead, etc., which levels are set forth in Table I below. These levels are aubstantially lower than those found in the particles described above for use in the rubber industry where toxicity is not a concern. Applicants' particles, having the requisite levels of these trace metals for use in the present invention, are therefore referred to in the present specification as substantially "pure". This substantially "pure" material is thus suitable for application to human skin since the trace metal content is maintained at or below the levels set forth in Table I below, that is, below levels which are likely to cause dangerous effects in humans.
Zinc oxide particles of the size and morphology described below, with such reduced levels of trace metal contamination, have not been previously known in the art, as far as applicants are aware. There has, in fact, been no call for this substantially pure form of zinc oxide since, as described herein, the use of this visually transparent W-W095128gl2 ~;A~ 1 8 8 1 6 6 P "~ .e~
. _ sunblock material was not previously contemplated by those - working in the sunscreen or the cosmetic fields.
In a preferred: ~ ; L, applicants' substantially pure zinc oxide particles are formed having a ~ubstantially spherical shape. This shape is preferred because it provides a smooth "feel" on the skin of the user. A variety of other crystalline shapes, such as needles, rhomboids, etc., have also been found to provide acceptable W protection, however, and may be utilized in the formulations of the invention as well, although as noted above, spherical particles are the most preferred. On the basis of the optical properties of the substAntiAlly pure micronized zinc oxide particles developed by applicants, ziul.s~ en ~ lu- Ls formed with this material remain visibly ~Lallzi~aLellL on the skin while attenuating a greater portion of the WA and WB radiation than was previously possible with the use of prior art sllnhlorlr compositions, without resulting in any adverse effects caused due to ~ '1 absorption. This result is not p~ ~s; hl ~ with the only other commonly used metal oxide, i.e., titanium dioxide, due to the different, i.e., less effective, optical properties exhibited by titanium dioxide .
Another ~ nt of the present invention is directed to the formation of physical sunscreen products comprising a particulate zinc oxide sunblock, preferably spherical in shape, having a ~ r of an order of magnitude greater than the "standard size" (i.e., 0.01-0.9~) particles used in _ _ _ .. ... .. ..... _ _ _ _ _ . _ _ _ _ WO9S/28912 ~ .,,~'C:E12 ~2 1 ~8 l 66 prior art sunscreen compositions described above. The particles used in the subject Qmho~ L are thus also substantially larger than the micronized particles described f or use with the previous ~ `- c ~ ; - L , i . e ., they measure at least about 1 micron, and preferable between about 1-100 microns in ~ 'Q . At diameters above about 100~, the optical performance of this material appears to deteriorate ~omewhat .
What is required, however, is that these particles be ~L~aLed by a process, such as gas phase chemical vapor deposition (CVD), spray pyrolysis or sol-gel particle rormation, which results in the formation of ~y LLical, ~ubstantially "optically perfect" crystals which are essentially free of internal fractures and/or other physical imperfections, and which have a relatively smooth outer ~urface. Such crystals, as a result of their morphology, have the required optical properties for use with the ~Ull~ ll formulations of the present invention, i.e., they attenuate a substantial portion of the ultraviolet radiation to which, they are exposed, which, as noted above, is greater than that which is attenuated with the use of prior art sllnhlo~ k products, while L- ;n;n~ tra~ aL~,~L in the range of visible wavelengths.
In addition, the relatively large crystals of the subject I '; L are also substantially pure as described above and thus contain only ;n-ign;ficant amounts of the trace metals listed in Table I below. The "purity" of these W095128912 . . ~1 88 1 66 P.~ -12 ~ ' , .

particles renders ~u..D-L~en formulations containing this - ~unblock material suitable for topical application to human skin without danger due to tr~ncrlorr~l absorption of trace metals. The substantially pure zinc oxide particles are S in~.uL~uL~ted into a liquid carrier, such as the emulsion described above, to form a visibly tranD~ar~l.L sunscreen formulation capable of attenuating a substantial portion, if not all, of the ultraviolet radiation directed upon the skin of the user to which this material is applied.
Alternately, in a further ~ ` 'i L, particles of a visibly transparent W-attenuating glass may be substituted within the ~ n for the zinc oxide particles described above. The glass particles used in the subject: -'i L
have an average diameter ranging between about 0 . 01-lO0 microns. They must also possess a relatively smooth outer surface and be substantially free of internal fractures or other physical imperfections. One well-known optical glass composition which has been shown to provide the desired results is referred to as Corning BK-7 (i.e., borosilicate crown-7) glass. The formulation of this material is well known and thus need not be described herein.
A still further . ' ' i - L of the present invention comprises a physical sunscreen formed with a plurality of small, visibly clear or colored plastic spheres measuring between about 0. O1-100 microns in rli, Pr. To obtain the proper optical performances, one or more W-attenuating '-, which may be chosen from a variety of materials _ WO95/28912 j CA2 ~ 88 1 66 PCrNS9~ 4842 well known in the art, are incuL} uLated into the plastic used to form these spheres. The W-attenuating ', once in~uL~uLated into the plastic spheres, has reduced potential to react with or be absorbed by the skin. These W-attenuating spheres are then dispersed in a liguid vehicle, such as the emulsion ~; Ccllcc~d above, to form a visibly LLU~Ia~aLeI~t D~.D.,.aen lotion which may be topically applied to prevent ultraviolet radiation from reaching the skin of the user.
All of the particulate materials described above for use in the sunscreen formulations of the present invention may also be in- u-yuL~ted by known blPn-ling methods into a variety of cosmetic products such as lipstick, eye-shadow, foundations, moisturizer, rouge and the like to form cosmetics having an increased ability to prevent damage to underlying skin by the action of solar W radiation. In addition, coloring agents may be in~lllA~ in the formulations described herein. For example, a coloring agent may be added to a matrix material prior to formation of a particle comprising the matrix and a W attenuator, such that the coloring agent is contained in the particle itself.
Alternatively, the coloring agent simply may be added to the plurality of particles after particle formation. Examples of coloring agents useful according to the invention include conventional cosmetic coloring agents such as various iron oxides, ferric or ferro cyanide blue, Ul1LI illm oxide greens, and FD&C colorants.

wo 95/28912 P~ ~ 7 ~ ~
'' 1:' C,~188166 D7~TATT T n DEStlRTPTION OF T7~7~ 73MBODIMENTS
- In selecting particulate materials for use in forming Arpl;cAnts' l)z,u..7~;L-~n products, and 2) ~ ; r formulations cnnt-7;n;n~ the sl7nhloc7~in~ agents of the invention, three optical properties, i.e., the absorption, r~f~ect;nn and refraction of these materials must be considered .
With regard to the f irst of these properties , i . e ., optical absorption, it will suffice to note that, for ~lL~oses of the present invention, this parameter is defined by a characteristic optical energy known as the "bandgap"
energy. S~m;cnn~7llr-tor materials such as the metal oxides, the visibly transparent glasses (e.g., BK-7) and W-attenuating plastics described herein are LLc~ aLellL to wavelengths above this bandgap value while they absorb energy having a wavelength lower than the bandgap energy. Thus it is preferred to use materials who6e bandgap energies are such that they remain visibly LLc~ ~dL~llL while attenuating wavelengths of light below about 400 nm, i . e., in the ultraviolet range.
Optical r~fl~ct;n77 and refraction are the L~ ;n;n~
properties which must be taken into account in predicting the performance of the particulate materials chosen for use in the present invention. With regard to these properties, it is important to note, first, that the ability of a particle to reflect light is affected by the morphology of the surface of the material of which the particle is formed, by the angle WO 95128912 1~ 'O I- ~2 `- CA;-~188166 of light incident to the surface of the material and by the difference in the index of refraction of the material ~d to that of the liuLLuullding media. That is, the closer the refractive index of the particulate material is to that of the medium in which it is s~l~p~n~ , the less visible contrast there will be. Formulation bases for use on human skin typically have a refractive index of no greater than about 1.6 while the refractive index of titanium dioxide is about 2 . 5 and that of zinc oxide is about 1. 9 .
Secondly, particles, i.e., crystals, formed with rough surfaces or having internal fractures or other physical imperfections will scatter incident light more than smooth particles and/or those lacking such fractures and imperfections. In some ~ Ls of the invention, it is thus preferred to use particles having a substantially smooth outer surface which are relatively free of internal fractures and imperfections in the present invention. This enables JU115~ ll products formed with these sllnhl orlc materials to attenuate a substantial portion of the W wavelengths to which the user is exposed while l~ in;n~ substantially transparent on the surface of the skin. After an extensive review of the literature in this field, applicants are aware of no t~chin~ or suggestion to utilize zinc oxide particles o~ the type described herein in applications such as those contemplated by Applicants, namely as a L of: 1) transparent tiu..s~ en formulations or 2) cosmetic compositions capable of providing an ~nh;~nr~d degree of WO 95/28912 i ~ r~ 12 ' ~ A2 1 88 1 66 protection from solar rays. Nor are Applicants aware of any - t~A~hin~ or suggestion in the art to use solvent-free -nr~r~ Ated W-i~ttenuating agents in a L~ullseLèell or: ~ ir formula. Thus, the use of applicants' particles in the manner indicated provides totally ulleA~,e~;Led results with regard to the ability of this material to protect the user against the effêcts of solar radiation crmt~;n;n~ W
wavelengths .
Suitable carriers for forming the emulsions described herein include SD alcohol, lanolin, glyceryl stearate, cocoa butter, sorbitan sesquioleate, propylene glycol, mineral oil, isopropyl myristate, petrolatum and acrylic polymers.
Mixtures of two or more of these materials may also be used.
These materials are known in the art as being "dermatologically suitable", i. e., they do not cause or promote adverse reactions upon the skin of the user.
The amount of the carrier need only be sufficient to provide a uniform dispersion of the particles when they are applied to the skin to ensure adequate e~ve:L ~e of the skin with the W-attenuating material. The particulate material preferably comprises no more than about 20% by weight of the total: 1 ~inn and preferably between about 1-10% by weight thereof. The only real limit on the lower end of this c~ L~tion range is that a sufficient quantity of the particulate must be ;nrl--APd to permit the formulation to attenuate the desired amount of W light. Concentrations of W095128912 ~ A 2 1 ~ 8 1 6 6 F~111J~ _~01~2 less than about 1% by weight of the total composition may even be useful in some instances.
F~AMPT F' I
For those ' '; Ls of Applicants' invention in which zinc oxide is a featured ~, the substantially pure zinc oxide of Arplic~lnts' invention, i.e., having a minimal trace metal content as set forth in Table I below, is preferred for use herein in order to take advantage of the abrupt transition which zinc oxide undergoes from reflector to absorber at a bandgap energy cULL~ in~ to a wavelength of about 335 nm, i . e., substantial~y at the border between the W and the visible regions. This bandgap energy value is in marked contrast to that of titanium dioxide, which does not show the same sharp change in triln~ ion upon entering the ultraviolet region (see, e.g., Brown, Harvey E., Zinc oxide: Properties and Applications, pp. 11-12 (1976) .
One drawback to the use of this material, however, is that titanium dioxide absorbs neither as much W-radiation nor transmits as much visible radiation as, for example, zinc oxide, which is utilized by applicants in the present invention (see, e.g., Brown, Harvey E., Zinc Oxide:
Properties and Applications, pp. 11-12, FIG. 2-4 (1976).
Thus, although the use of micronized titanium dioxide particles does render the resultant product smoother and less occlusive, it does not obviate the main drawback faced with the use of this material , i . e., its - ~tively lower ~WO95/2~912 CA2188166 r~ Q~

effectiveness (in CUIILL--L to ZnO) as a sunblock agent.
Titanium dioxide-based products are also more opaque than those formed with the zinc-oxide of the present invention, which is due to the fact that the crystalline aLLu~:LuL~ of the titanium dioxide material renders it only partially tran,,~aL-..L to visible wavelengths of light and thus not generally as acceptable for cosmetic use.
Although it has been known to form micronized particles of zinc oxide for very specialized uses in the rubber industry, those particles contain substantial quantities (i.e., greater than about 200 ppm) of trace metals such as lead, mercury, arsenic and cadmium. The potential dangers to human health caused by ~O-UL~ to these materials is well ~ ted. Thus, such zinc oxide particles containing these levels of trace metals are not acceptable for topical application to human skin.
A further advantage to the use of zinc oxide over titanium dioxide in some of the sunblock formulations of the present invention is that zinc oxide is substantially less expensive than titanium dioxide, thus providing a significant cost cavings with the use of this material in applicants' invention. Still further, as noted above, applicants' substantially pure micronized zinc oxide particles contain a substantially lower amount of trace metals than is typically found in the specialty purpose micronized particles of this material. The use of such prior art micronized zinc oxide is, as rl~ccllcced above, not possible because of the ~ ~ 2 1 ~
wo 95/28912 Pcr/usssl04842 toxicity of this material due to the relatively high uu.,cel~LL~tions of trace metals contained therein.

Applicants have discovered, with respect to one i- L of the present invention, that their substantially pure micronized particles of zinc oxide (described below), when dispersed in a dermatolo~ lly suitable liquid carrier in the form of a colorless l~inn, form a visibly ~L-IlDLJar-:llL DullsuL~el~ when applied to human skin. As used herein, "visibly tranD~a~..L" refers to the optical ~L~ LLy of visual transparency when the formula is applied in a thin film ti.e., ~ 100 microns, preferably < 20-50 microns). This formulation is capable of attenuating a substantial quantity, if not all, of the W radiation to which the user i8 exposed.
As noted above, these zinc oxide particles are preferably spherical in shape to provide a "smooth" feel to the product and to facilitate its application onto the skin, but non-spherical particles, such as needles, squares, rhomboids, etc., may also serve the required purpose, although they are not as pref erred .
Although, as noted above, micronized particles of zinc oxide are known in the art for specialty applications in the rubber industry, such particles contain elevated levels, i.e., greater than 200 ppm, of toxic trace metal contaminants. These trace metals include lead, cadmium, mercury and arsenic, all of which are known to be hazardous to human health. In contrast, the "substantially pure" zinc oxide particles developed by applicants for use in the WO95/28912 ~A?~ 8 ! 661r it ~ 6 r~ clc:~12 present invention, whether in the form of micronized particles or a6 larger, "optically perfect" particles as described above, contain no more than the following range6 of the trace metals listed below.
TABLE I

Lead <20 ppm Arsenic <3 ppm Cadmium <15 ppm Nercury ~ <l ppm .

WO95/28912 ` ~ C A ~l g g l 6 6 ` ~ ,5l01-~2 l; X ~MPT .F: I I
Another = i L of the applicants ' 8llnhlork formulations comprises substantially pure particles of zinc oxide, preferably spherical in shape, having a diameter substantially greater by at least an order of magnitude than the "standard" sized zinc oxide particles used with prior art ~ul~8~iL~ell compo6itions described above and about two orders of magnitude greater than the micronized zinc oxide particles. Thus, the zinc oxide particles preferred for use in the subject t~o~ t of the invention measure at least about 1 micron in diameter, and preferably between about 5-20 microns. The upper end of this range is not critical, however, and thus the subject particles may range up to 50 or even 100 microns in diameter. Fur~h~ ~, the particles need not be spherical, although that shape is preferred since it facilitates application of the sllnhl c~k composition onto the skin when the zinc oxide particles are dispersed in a liquid carrier such as the emulsion ~ i ~cllcced above. The c~ ellL, c.tion of these particles within the : 1 c; c~nc is essentially the same as that used for the: i-- L
utili~:lng ~icronized zinc oxide, i.e., between about 1-10%
by weight .
As noted above, the bandgap energy value of zinc oxide is such that it changes from transparent to opaque at approximately the border between visible and W light.
However, as previously tliccllcFod, if the zinc oxide particles have rough surfaces or if they have internal fractures or WO95/28912 ; ~7A 21 8 8 1 6 6 other physical imperfections, these features will contribute to the scattering of incident light and a ~UIISUL.~el~ product formed of such a material will thus not be vi6ibly LLall'--~a~llL.
In order to uv~L~ - these difficulties, the ~ubstantially pure zinc oxide particles of the subject ;r L are preferably formed with the use of a chemical vapor deposition ("CVD") technique, which results in the formation of symmetrical particles of zinc oxide having a diameter within the range noted above, which appear visibly clear upon the surface of the skin while r~ inin7 capable of attenuating a substantial portion of the W radiation to which they are exposed. These particles are thus considered by applicants to be subs~AntiAl ly "optically perfect" for the ~uL~oses of their invention.
In the CVD process used with the present invention, zinc source compositions are i..-Luluced as vapors into a heated reaction volume, i.e., chamber, where they react with oxygen, typically supplied as a gas, to form the zinc oxide particles described above, i.e., ranging in size from about 1 to about 100 microns. The driving force ~or this reaction can be the exothermic formation energy of the zinc oxide product itself or this energy may instead be supplied by external sources such as thermal or radio frequency (RF) plasma energy. The entire process may be automated and computer controlled in a manner known in the art.

wo95n89l2 ,~ 2 1 8 8 i 66 ~ u~ - o~e12 More specifically, the CVD process utilized by applicants may utilize, as a zinc source, compositions such as zinc acetate, zinc chloride, zinc oxalate or Ul-, ' ll;n zinc _ '~ such as dimethyl zinc t"DMZ") and diethyl zinc ("DEZ"). Applicants have dotQrm;nPcl that zinc oYide formed with the use of CVD from an org~- ~ ll;r zinc source will achieve particles having high growth rates at relatively low growth t~ ~tUL~:s, i.e., below 500 C and are thus preferred. The zinc sources used are thus preferably DMZ and DEZ, whereas the oxidating gas may be relected from among gaseous water, oxygen and alcohol.
6ince both DEZ and DMZ are liquids, they are contained, prior to use, in a conventional bubbler device, typically maintained at about 20 C, whereupon they are subsequently transferred to the reactor via a carrier gas such as nitrogen or argon which is bubbled through the liquid. Water vapor iB introduced to the reactor in a similar manner. The zinc and ~ l;7Qr source ~-hQm;c~ are injected into the hot reaction chamber through separate nozzles where they mix and react to form the zinc oxide particles. The ratio of nY;~l; 7;ng gas to the organometallic zinc should be greater than about 7:1, preferably about 10:1, in order to completely oxidize the zinc. The reaction t 'tUL~ may range from about 180 to about 500 C, with the preferred range being from about 300 to 400C. The reaction pl~s,,uL~ can range from 1 torr to about 760 torr. For purposes of simplifying the apparatus, however, ~,i ,'-ric pLt:sz~ULc is preferred.

WO 95/28912 C ~ ~ 1 8 8 1 ~ 6 ~ ; ~ 12 The desired zinc oxide particle size is achieved by (1) --n;rl~lAting the amount of reactants used by, for example, a mass fl_ l c~,..LLoller, and (2) the residence time of these materials in the reactor. The relat ion~h;r between these parameters is such that, for example, increasing the amount of time the reactants spend in the reaction chamber will result in a proportional size increase in the zinc oxide particles, having a d;; '~r ranging in size from about 1-100 microns, are formed with a substantially smooth outer surface and, in addition, are substantially free of internal fractures and/or other physical imperfections. ~I-L~ V~', if desired, an antireflection coating of, for example, silicon oxide may be applied to the surf ace of these particles to reduce the optical reflection rrom the material/media interf aces which thus renders them even more transparent to visible light.
Alternately, in place of the CVD process described above, acceptable zinc oxide particles may be formed with the use of other conventional ~JL ocessed such as spray pyrolysis (see, e.g., Eberspacher et al., "Pyrolysis of ZnO Film Deposited Onto InP By Spray Pyrolysis," Thin Solid Films, 136 (1986, pp 1-10) or sol-gel particle formation, both of which are well known to those skilled in the art.
IlJr ~Vt:L, it is important to note that although zinc oxide and other metal oxide compositions have previously been commercially utilized in the form of relatively thick visibly LL ~IID~" L :nt layers used, f or example, in f orming heat mirrors W095128912 ~A21~881 66 r~_l/U~._'O~e~2 ~; , .! i '~ "/

in architectural application6 and as transparent electrical c~n~7l7rt~rs for solar electric applications, the present invention i~ directed to the formation and use of separate, dispersed substantially pure zinc oxide particles in a liquid carrier to serve as a visibly transparent, W-attenuating E~1nh10r~7~ ISJLeU~ the inclusion of such relatively "optically perfect" visibly transparent, UV-attenuating particles of zinc oxide in ~u--~- L~en compositions of the type described herein has not, to applicants' knowledge, been contemplated anywhere in the prior art.
7z-~7~7LE III
In a further 7~o~7;- L of the invention, particles of a visibly transparent glass having a bandgap energy at about 400 nm, tlus permitting it to aLL~I-uate W light while ~ 7n7ng virtually transparent to visible light, may be dispersed in the carrier in place of the 1-1OO~(L zinc oxide particles described above. The diameter of the glass particles preferred for use in the invention may range between abGut 0 . 01-lO0 microns . In addition, these glass particles must have a substantially smooth outer surface and be ~,u7~DLcll tially free of internal fractures and other imperfections. Any such optical glass meeting the requirements set forth above may be utilized, although borosilicate glasses such as the visibly tranD~a_~.L Corning BK-7 material described above are preferred for use with the present invention . The entire-f lective coatings described WO95128912 ~ - tÇ ~ 21 ~38 1 66 r~ t~42 . ;, .
above may also be used to coat the optically active glass particles of the type described herein.
MPT.R IV
Another . ~ i- of the invention comprises a sunscreen lotion ; n~luA; n~ a plurality of com~nercially available plastic particles preferably, although not n~c~ silrily, spherical in shape with a ~ r ranging between about 0.O1-1OOIL, formed, in part, of a visibly transparent plastic. Such plastics are well-known in the art and may include, for example, acrylics such as polymethyl methacrylate ("PNMAIl); styrene polymers; copolymers of styrene and acrylic; styrene acrylonitrile ("SAN");
polycarbonate; methylpentene; terpolymers of acrylontirile, butadiene and styrene ( "ABS" ) and allyl diglycol carbonate (nADC"). The invention should not, however, be limited to the use of these plastics, as any visibly LL~ a~ plastic having, or capable of being modified to have, as described below, the desired optical properties to render it visibly transparent but capable of attenuating W radiation, is suitable for use in the present invention.
In order to control the W attenuating properties of these plastics, one or more W absorption additives, also known as "W stabilizers", may be incorporated into the plastic used to produce the spheres during their formulation.
Although it has been previously known in the art to add W
stabilizers to plastic substrates, such as in the formation W0 9~128912 ' ' ` ~ 'A ~ 1 8 8 1 6 6 ~ 2 of large sheets of W-absull.e.,~ plastic, the inu~L~,uL_tion of such W stabilizers into small plastic spheres of the type described herein has not been previously known for use in ..UJI8~ . .en applications .

E~AMPT ~ V
Yet another ' i - ~ of the invention comprises a &~U~IUL~ lotion in~ n~ a nu-.suL~en -nt comprising a plurality of suns.L~ r~ ated particles preferably, although not n~ rily, spherical in shape with a di: ' or ranging between about 0. 01-100~, formed, in part, of a visibly ~L~In~ar...~ or a colored capsule matrix. Matrices useful for ~n-_rF~ tion according to the invention have general properties, as follows. Such matrices can be rendered water-dispersible; are relatively chemically inert, i.e., will not react with other null5ur ~=~" formula ingredients; are able to form a water-tight capsule such that ~unscreen formula ingredients cannot enter the capsule; are able to resist deuL a-l_tion by and thus to hold an organic or inorganic ' in its interior; and may also posses6 ~ tactile gualities in admixture with a sunscreen n. In addition, certain preferred matrices may possess the following characteristics: i.e., a preferred matrix is preferably essentially non-water soluble (i.e., <
5%); has a melting point preferably below 100 but not above 200 degrees Centigrade; and has a viscosity of less than 500 cp. at a temperature less than 100 degrees Centigrade. Any .. _ _ . _ .. _ . _ . . _ . _ _ _ . .. ... ..... . .. _ .

wo 95/28912 1:~ ~ 2, 7 8 8 7 6 6 P. l/.), 1512 ~ ; -- 3 5 --material that does not posses6 these characteristics alone may be '~; necl with another material to produce a mixture having all of the~e characteristics. Preferred matrices have desirable qualities such as W- or IR-attenuation properties.

r l~C of ~nrAr~ ting matrices useful according to the invention include matrices that are ~ ` ~nAhle vith a W-attenuating sunscreen according to methods of manufacture that do not require solvents for formation of a capsule.
Such solvent-free methods of manufacture involve formation of the c-n~r51- 1 Ated ~ul~ ro:ell by a melt process .
The matrices include wax matrices, as described below, as well as polymer matrices such as commercially accepted natural oils and their derivatives (i.e., l~ydL~ lated or oxidized) and synthetic oils, and lipid and protein derivatives. Natural oils include but are not limited to plant-derived oils, such as castor, soybean, sesame, safflower, wheat germ, etc.; synthetic oils include but are not limited to sj 1 iConDc~ cyclomethicone, etc.
other ~L~reL _d matrices include but are not limited to materials that are ~n~-Ar~-1lAtors according to a solvent-free process , e . g ., polymeric materials such as alkylated vinyl pyrrolidone polymers (e.g-, C20-C30); long chain (e-g-, C~4-C50, preferably C20-C30) alcohols; long chain (C;4-C30) fatty acids;~
propylene glycol ester of fatty acids; ethene homopolymers (e.g., mw > 400 g/mole); various grades of polymerized alkenes and alpha alkenes with molecular weights greater than W0 95128912 C A ~ 1 8 8 1 6 6 1~11. c :E12 100 g/mole; ethylene-acrylic acid copolymers (Allied Signal AC 400 series); and ethylene-vinyl acetate copolymers (Allied Signal AC 400 series). The invention 6hould not, however, be limited to the use of these matrices, as any ~nrArsl~lAting matrix having, or capable of being modified to have, as de~wribed below, the desired optical properties to render the ~nr~p~ ted W-attenuator capable of attenuating W
radiation, yet dispersible in water, is suitable for use in the present invention.
The ~atrices described herein are not by nature dispersible to form a stable dispersion in water. Therefore, the invention includes the use of surfactants, e.g., anionic, nnn;~mic~ or cationic, or combinations thereof, to provide a useful degree of emulsification and con~ nt stability of the resulting particles. Surfactants useful in the invention will be of the type commonly used in the cosmetic industry, i.e., cosmetically acceptable. Examples of acceptable surfactants are provided in McCutcheon's Catalog of Emulsifiers and DeLeL~el~Ls~ NC pl~hli~hing, NY, Vol. 2, 1993, the contents of which are hereby inCULU~L~lted by ref erence .
In order to control the W absorbance properties of an ~nrAre~ Ating matrix according to the invention, one or more W aLLe..a~Ling additives, also known as "W st~hili7~rs", may be il~uL~uLclted into the matrix used to produce the particles during their formulation. The incuL~ulaLion of such W
stabilizer6 into matrices of the type described herein _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ W0 95/28912 ~ ~1 2 1 8 8 1 6 6 ~ -rQ4e~7 ; ..~ 37 -according to solvent free processes has not been previou61y known for use in .,u~ Lae.- applications.
W additives are well known in the art (see, e.g., Modern Plastic EncyclopP~ 1976-1977, pp. 222-227 and 708-709 and U.S. Pat. No. 4,882,143 to Kadokura et al., col. 7 lines 61-65) and include materials such as derivatives of ~alicylic acid, benzoic acid, ~nn~ c acid and bon7~rh~non~
benzotriazoles aryl esters, substituted acrylonitrile, - 11 i c complexes and inorganic pigments . The invention should not be limited to the use of these specific materials, however, since any W additive which serves the intended purpose, i.e., attenuating ultraviolet radiation, can be used with the formulations described with regard to the subject ~ - ' i r L of the invention .
A DUIIS-,L~ L of the invention will include particles of a visibly transparent or colored matrix and a W-attenuating agent which may be made according to any solvent-free method that is known in the art (e.g., see Slivka, 1975, Chem. Internat. Ed. 14:539), inrlll~linq spray-drying (see, e.g., Brenner, Perfum. Flavour, 8:40, 1983), and coacervation, e.g., the conv~nti~n 11 gelatin/gum arabic method (Bl~n~Dnh~rg de Jong, in "Colloid Science", Vol. 2, H.R. Kruyt ed., Elsevier, Amsterdam, p.244, 1949, and U.S.
Patent 2,800,457), all of the above references of which are incoL~uLated by reference. These methods may result in particles that are larger than desired, in which case modifications of other solvent-free methods may be preferred, -C~21 881 66 W095128912 ~ j r~ J. 'C~17 e.g., melt-chill Pn~ ArS~ tiOn, described in U.S. Patent 3,865,799, herein irlcuL~UL ated by reference.
The melt-chill Pn~-Ars~lAtion method disclosed in 3,865,799 may be modified and thus; u._d to allow for production of particles having a tl i ~ range that is smaller than the 20-500 micron diameter range particle described in 3,865,799. For example, one 8uch i , method that is particularly useful for matrix materials such as waxes involves ~;nin~ the molten onr~rsl~lAting matrix material with a pre-heated aqueous phase to delay immediate formation of relatively larger particles that form as a result of _ ';nin7 molten material with a cool aqueous phase, as described in the prior art. This delay of particle rormation allows for increased control over particle size, the control being PnhA~nPd by the use of surfactants in the process. This and other i u. L8 are described below.
The matrix material, e.g., at a culn:el~LLa~ion of 1-50%
of the formulation, is, ' inP~ with one or more W-attenuator~, e.g., at a final ~ ation of 1-20~. The mixture is heated to a t~ atu~c required to melt and liquify all materials. The combination is then mixed to provide a h~ , ~ oil phase. The oil phase may also contain oil-soluble surfactants, e.g., at a .u-lcellLL~tion of 0.1-10%. A quantity of water, e.g., 40-90% of final formulation, iB separately heated to the same or a higher t~ aLuLe as the oil phase, the temperature preferably does not exceed 100 degrees centigrade. The water phase may WO 95/28912 I; C A 2 1 ~ 8 1 6 6 r~ ~2 contain water-601uble surfactants, e.g., at collc~,lLLc~tions within the range 0.1-10%. Maintaining temperature, the oil phase is emulsified into the water phase using a high speed mixer, colloid mill, homogenizer, or ultrasonic pLoces~uL.
Once the emulsification is complete, the resultant fluid is cooled to room tr ~LUL~. Cooling results in golidification into discrete small particles of emulsion droplets of molten matrix and W-attenuator materials, the particles being dispersed in an aqueous continuous phase.
Alternatively, the ab~ des- Libed melt-chill process is ~odif ied by heating the matrix material to melting t~ ''LUL~ and then . ' ~nln~ the liquified matrix material with a solid particulate W-attenuator. The W-attenuator may be dispersed in the liquif ied matrix material using a high speed mixer, colloid mill, 1 J ni ~er, or ultrasonic ~cesso~ . The oil phase may also contain oil-soluble surfactants, e.g., at a c~,l.c~..LLc.tion of 0.1-10~ to enhance the degree of dispersion of particulate material and/or emulsification. A quantity of heated water is added, and the oil phase emulsified into the water phase as above. Once emulsification is complete, the resultant fluid is cooled to room temperature. Upon cooling, droplets of the ~ inn solidify into discrete small particles which are dispersible in an aqueous continuous phase.
It also will be understood that the above-described ocesses may be modified (1) to allow for two or more W-attenuators to be ~-in~ in the same particle; and (2) to W095/28912 P~ll~., 5'Q: ~7 `~A21 88l 6~ --allow for two or more ty~es of matrix materials to be ' ;n~A irl a particle.
Additional; _uv. Ls that have been discuveLed for the aLuv~ des~ lbed ; uved melt-chill process are as follows. In the case of organic sunscreen material, ~pec;Ally solid crystalline materials, solllh;l;~;ng materials, such as those found in McCutcheons Catalog of Functional Materials, 1993, pp. 238-248, may be ;n~ AP~A~ in the particles to increase the solubility of the crystalline materials in the particles, thereby reducing the potential of the ~iu~lDur .~n material to recrystallize in or from the particles. This is Q~peri:~lly true for those materials that occur as highly A~iC~IlAr crystals; A~ic~ r shapes have a strong thëL :y-la~ic tendency to exist in crystal f orm.
Useful 50lllh; 1; ''orS will be good solvents for the W
attenuating ' (8) and will have little and preferably no water solubility.
In the case of inorganic particulate materials, an u~v~ l. of the melt-chill process involves pretreatment of the inorganic particulates with a l-ydr uphobic c such as silane. Silane covalently binds to the sur~ace of the particles and converts inherently hydrophilic inorganic oxides to a ~Iy-lLu~hObic state. It has been diDoc VeLed that pretreating these inorganic agents with a hydrophobic _ ' in~, .aa~ the degree of dispersion of the inorganic particles within the matrix. This pretreatment improves both final particle sise as well as completeness of encapsulation, _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Wo95128912 ~ ~ A2 ~ ~8 1 66 1 ~u~ E12 and thus also improves isolation of these materials from ambient conditions. Silane l~yd~u~l~obing ~ _ '~ can be applied to the inorganic oxide particulates either by vapor L~=a or from solution.
Wax matrices useful according to the invention include, but are not limited to, natural and synthetic waxes that contain mixtures of alkyl wax esters, resins, and other vegetable matter : Li; clay-treated microcrystalline waxes; nYi~l; 7Pd ~l~d.u.el~Lûll waxes; natural and synthetic beeswax, auto-oY;~;7~cl beeswax, rAnAPl;l;~, carnauba, and synthetic waxes ~ d by esterification of natural plant-derived f atty acids and alcohols; various grades of paraf f in waxes; and matrices ;nnll-A;n~ lipids, proteins, and their derivatives. ûther materials included herein as examples of waxes, comprise, e.g., polymeric materials such as alkylated vinyl pyrrolidone polymers; long chain alcohols; long chain carboxylic acids; propylene glycol ester of fatty acids;
ethene homopolymers; various grades of polymerized alkenes and alpha alkenes with molecular weights greater than 100 g/mole; ethylene-acrylic acid copolymers; and ethylene-vinyl acetate copolymers.
Provided below are examples of; uv~d melt-chill ~u~ ~sses according to the invention. The process is selected ~lorPnA;n~ upon the physical and rhPm;r~l characteristics of the W attenuating material to be Pnr~rs~ ted.

WO 95/28912 ~ ' A 2 l 8 8 l 6 6 r~ ,7 E~MPT ~ VI
For liquid organic W attenuating materials, 5 gms of the organic W attenuating material Escalol 557 tOctyl Methoxy Cinnamate-ISP Van Dyke) is i n~ with 5 gms carnauba wax (Roster Reunen). The combination is heated to 90 degrees centigrade to form a liquid state and mixed to h- , lty. Separately, 90 gms of do~ni7~ water is ~nD~l with 4 gms of the non;On~ emulsifier polyoxyethylene (23) lauryl ether (Bri; 35-ICI Americas) and also heated to 90 degrees centigrade. The two phases are inP~, maintaining temperature, and emulsified using a high speed mixer (Omni 5100 mixer, Omni International, Gainsville, VA, with a 10 mm ~ii Dr generator probe, at a setting of 8) for 5 minutes. The resulting emulsion is then allowed to cool with stirring to room temperature in order to solidify the F 1 ~:ion droplets of OMC and carnauba wax into discrete particles. The resulting OMC cul.cel.Ll~tion is around 5% which can be increased by evaporation of the water continuous phase.

Wo ss/289l2 ~ ~ - P~ 52 CA21~3t66 E~MPLE VII
For solid organic W ~tLc ..uctting material with ~oltlhi 1 i 90r~ 5 gms of the organic W attenuating material Escalol 567 tbons~ r 3 - ISP Van Dyke) is combined with 15 gms of the 801-lh; 1 i ~or Ceraphyl 368 (octyl palmitate-ISP
Van Dyke) as well as 20 gms o~ carnauba wax (Koster Keunen).
The combination i8 heated to 90 degrees centigrade to dissolve the bon9 ~ r 3, form a liguid state, and mixed to k ~, ity. Separately, 60 gms of ~loinni ~-od water is ~- i ned with 5 gms of the nonionic emulsi~ier polyoxyethylene (Z3) lauryl ether (Bri; 35-ICI Americas) and also heated to 90 degrees centigrade. The two phases are inod, maintaining temperature, and emulsified using a~
high speed mixer (as in Example VI) for 5 minutes. The resulting emulsion droplets of octyl palmitate and carnauba wax matrix and bPnsorhon~no-3 into discrete particles. The resulting bon~orhol~ono-3 .u-~ Lcltion is around 5% which can be increased by ,:v~t~u ~tion of the water continuous phase.
E~MPT.~ VTTT
For solid inorganic particulate W attenuating material, 15 gms of Polywax 500 (polyethylene wax-Petrolite) and 1 gm of the oil soluble nonionic di~ r.clllL Capmul GM0 (glyceryl mono/dioleate-Karl~:h~ - USA) are ~-;ned and heated to 90 degrees centigrade to form a liquid state, and mixed to h~ ~ i ty . To this melted liquid is added 5 gms of the inorganic particulate W attenuating material Z-cote wo 95/28912 ~ 1~ 2 1 ~ 8 ~ 6 6 P~ '0 :~2 ,~, `"

(microfine zinc oxide, sunSmart, Inc, NY~. The entire mixture is processed with an ultrasonic ~LvcessvL for 2 minutes in order to disperse the zinc oxide particulate material. Separately, 80 gms of ~3Pi~ni ~od water is ~ ' inPd with 5 gms of the nnn;nn;c emulsifier polyoxyethylene (23) lauryl ether (Brij 35-ICI Americas) and also heated to 90 degrees centigrade. The two phases are combined, maintaining t~ Lur e~ and emulsified using a high speed mixer (as in Example VI) for 2 minutes, followed by 1 minute using and ultrasonic processor. The resulting 1 lc;rn is then allowed to cool with stirring to room t~ c~LuLe in order to ~olidify the emulsion droplets of polyethylene wax matrix containing particulates of the zinc oxide, into discrete particles. The resulting zinc oxide vll- ellLr c.tion is around 5% which can be increased by allowing the hardened particles to settle, due to their high density, followed by decanting of f a portion of the water continuous phase .
Some of the particles described herein, i . e., those particles formed from conventional high melting point plastics ~Lv~uced by solvent-emulsification methods of manufacture or emulsification polymerization ~Lvcesses, inherently contain solvent or monomer rPC~ lc which are by nature toxic, highly irritating, or sensitizing to human skin. E~owever, the particle ~ L of Pnr; rs~ ted :~UIlS~Leell~ of the invention are easy to manufacture in that a capsule matrix may be chosen that is ~hle to preparation by less toxic methods of manufacture; for ~ w09s~28912 i ~ - ~ C d 2 1 ~ 8 ~ 66 r~l~U C~0,~,2 example, a wax matrix can be melted using conventional "melt-- chill" methods known in the art, thus eliminating the need for organic solvents. In addition, the products achieved via ~uch methods of l--nl~f~rtl~re are less toxic, an; L~..L
c nn~ ation for agents applied to the skin.
Nany ~-Y~ nt sunscreens are organic and water-insoluble, nnd thus are not compatible with water-based :~UIISUL~,_.I fOL lAe. Water-based ~u~s~Lee1.s are often preferred over oil-based sunscreens by virtue of their lower cost and certain aesthetic considerations, e.g., less gr~ inP~s. ~n-~r~ tion of a Dl..s~L~en agent in an inert wax capsule converts an oil-soluble DUI.-_L~ll agent into a water-dispersible agent. For example, the oil-soluble common organic ,u..scL~en octyl methoxycinnamate (OMC) was ~nr:~r~ Ated in an accepted cosmetic wax, U~ A~ at a ratio of one part OMC to one part carnauba wax. The OMC/carnauba wax particles were then modified with an aqueous gel of carbopol polymer, an aqueous soluble polymer of polyacrylic acid (BF Goodrich, Inc. ), at a resultant active ~ullue IlLL"tion of 5% ONC. It is to be noted that this simple formulation contains no additional ~ oil normally needed to formulate a ~u115- L-_ll with OMC. The sun protection factor (SPF) of the resultant sunscreen formula was det~rm;n~ by FDA ~Luv~cd methods on five subjects, and was 8 . 2, as shown in Table 1.
Inorganic sunscreen agents that may by nature be dispersible in either of the oil or water phases of ~

W095/28912 ~ 21 881 66 r~ c~ ~

conventional cosmetlc formulation are normally placed in oil in order to attempt to provide some degree of wateL~.L~orness to the particulate inorganic W attenuating agent. This invention, by the use of film-forming matrix materials for Qnrlrs~llAtion ti.e., that bind to the skin to provide wateL~o~r~less) eliminates the need to include the agent in an oil pha~e, thereby increa~ing the options for the ~ ir.
formulator in providing a waterproof C~U11i31.:Leell formulation.
~nrArclllAtion of t.u..s~;L~en agents also allows for m;n;m;~ation of undesirable chemical reactions between the sunscreen and other active ingredients in the sunscreen formula. For example, some ~UIIS~:L~el~6~ such a8 benzQFhPnnnQ, are known to form crystals in solution. Mowever, wax-~-nrArc--lAted bQn7~rhQnnne did not crystallize in solution.
Thus, QnrArc--lAtion of this organic . _ ' prevented its crystAll;~tinn in solution.
~nrs~p~ulAtion of Sull:,~;Lèel~ agents allows for control of ambient conditions around the -UIISI,. ~ell '_ L particles.
Thus, the invention allows combining of ~U~ISI.:Le_ll agents which when - ~l, lAted are rhQm;rAlly reactive such that they lose their W-attenuating propertie~i when '-; nQ~9, or cause other adverse reactions such as discoloration.
Individual ~nrArculAtion of rhQ~;CAlly reactive sunscreen agents allows the formulator to disregard these chemical reactivities, and to choose admixtures of any number of ~UIISI,;L .en agents .

W095128912 ''~ A2188166 r~L"'~ ~Q I~
The inclusion of additive materials into the plastic spheres or ~nri~rclll ating matrices described above serves to render these visibly transparent or colored particles capable of attenuating W radiation. Thus, upon dispersing these transparent, W-attenuating particles in a liquid carrier such ~s the . 1 ~inn described with reference to the of the invention u~ i n~ substantially pure particles of micronized zinc oxide, in a cul,c~.,LL~tion ranging between about 1-2096 by weight of the emulsion and, more preferably, between about 1-1096 by weight, the resultant formulation may be topically applied onto the skin of the user, whereupon it remains visibly tranD~aLe~.L or colored while attenuating a substantial portion of the W radiation to which the user is exposed.
Moreover, the particulate sunblock materials described above for inclusion in the topical sunscreen formulations of the present invention may, in still further ir- Ls of the invention, be in-u-~uL~ted into a variety of cosmetic pludu~ L~ such as, for example, lipstick, eyeshadow, foundations, moisturizers, rouge, hair products such as and conditioners, and other personal care ~ILUdUU~5 to enhance the ability of these formulations to protect the underlying skin of the user from the A~r-g; ng effects of W
radiation. These materials may be blended with the cosmetic base by known blending methods such as by meang of TTpncrh~
mixer, a ribbon mixer, a twin-cylinder mixer or the like.

w09s/28912 ~ '~; CA~I88166 P~ Q~
The amount of such particulate material present within the cosmetic formulations of the invention comprises no more than about 40i by weight, and preferably between about 1-20%
by weight.
The cosmetic formulations described above may also contain a variety of addltive materials. These additives are well-known in the art and are added for the purpo6e of performing their inherent fllnrti~-nR. The preferred additivea include materials such as thickeners, softeners, superfatting agents, waterproof ing agents, emollients, wetting agents and surface-active agents, as well as preservatives, anti-foam agents, pelL, - and mixture thereof, or any other compatible ingredient usually employed in cosmetics.
While it is dlJ~aL~..L that the invention herein ~liR~ 5~l is well calculated to fulfill the objects above stated, it will be appreciated that vus modif ications and s may be devised by those skilled in the art and it is intended that the ArrPn~ claims cover all such modifications and ~ s as fall within the true spirit ~0 and scope of the present invention.
~, , "--

Claims (25)

-49-

1. A component of a sunblock formula, comprising a plurality of particles having diameters in the size range of about 0.01 - 100 microns, each particle of said plurality of particles comprising a substantially homogenous mixture of a matrix and a UV-attenuating compound, said plurality of particles being solvent-free and dispersible within a dermatologically acceptable carrier.

2. A component of a sunblock formula, comprising a plurality of particles having diameters in the size range of about 0.01 - 100 microns, each particle of said plurality of particles comprising a substantially homogenous mixture of a matrix comprising wax and a UV-attenuating compound, said particles being solvent-free and dispersible within a dermatologically acceptable liquid carrier.

3. The component of claim 1 or 2, said plurality of particles comprising a coloring agent.

4. The component of claim 1 or 2 wherein each particle of said plurality of particles further comprises a second UV-attenuating compound that is incorporated into said matrix.

5. The component of claim 1 or 2 wherein said plurality of particles comprises a first UV-attenuating compound and a second UV-attenuating compound that are individually incorporated into said matrix to form first and second particles, respectively, comprising separately encapsulated first and second W-attenuating compounds.

6. The component of claim 1, said matrix comprising a material selected from the group consisting of: vinyl pyrrolidone polymer; long chain alcohol; long chain carboxylic acid; propylene glycol ester of fatty acid;
ethene homopolymer; polymerized alkene and alpha alkene having a molecular weight greater than 100 g/mole;
ethylene-acrylic acid copolymer; and ethylene-vinyl acetate copolymer.

7. The component of claim 2, said wax comprising a material selected from the group consisting of a natural and a synthetic wax.

8. The component of claim 7, said natural wax comprising a material selected from the group consisting of alkyl wax ester, resin, vegetable matter components, clay-treated microcrystalline wax, oxidized hydrocarbon wax, natural and synthetic beeswax, auto-oxidized beeswax, candelilia, and carnauba.

9. The component of claim 7, said synthetic wax comprising a material selected from the group consisting of synthetic wax prepared by esterification of natural plant-derived fatty acids and alcohols, and paraffin wax.

10. The component of claim 1 or 2, wherein said UV-attenuating compound is selected from the group consisting of organic and inorganic UV-attenuators.

11. The component of claim 10, said organic UV-attenuator being selected from the group consisting of benzophenone, cinnamate, salicylate, aminobenzoic acid ester, menthyl anthranilate, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, 2-phenyl benzimidazole-5-sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, 2-ethyl-2-cyano-3,3'-diphenyl acrylate.

12. The component of claim 10, said inorganic UV-attenuator being selected from the group consisting of metallic complex and an inorganic pigment.

13. The component of claim 12, said metallic complex comprising zinc oxide.

14. A substantially transparent topical sunblock formula for shielding skin from ultraviolet radiation, said formula comprising an effective amount of the component of claim 1 or 2 dispersed within a dermatologically acceptable carrier in at least an amount sufficient to shield substantially all skin over which said formula is applied from hazardous effects of ultraviolet radiation.

15. A method of making a substantially transparent topical sunblock formula for shielding skin from ultraviolet radiation, comprising dispersing the sunscreen component of claim 1 or 2 in a dermatologically acceptable carrier in at least an amount sufficient to shield substantially all skin over which said formula is applied from hazardous effects of ultraviolet radiation.

16. A method of shielding the skin from ultraviolet radiation, comprising spreading an effective amount of the substantially transparent topical sunblock formula of claim 14 or 15 over the skin sufficient to shield substantially all skin over which said formula is applied from hazardous effects of ultraviolet radiation.

17. A method of preparing the component of claim 1 or 2, comprising subjecting said matrix and said UV-attenuating compound of claim 1 or 2 to a solvent-free process to produce a solvent-free plurality of particles comprising said matrix and said UV-attenuating compound.

18. A process for preparing a component of a sunscreen formula, comprising the steps of:
(a) heating an encapsulating matrix above its melting point at a temperature in the range of 30 - 200 degrees Centigrade for a time sufficient to form a liquefied encapsulating matrix;
(b) mixing a UV-attenuating compound with the liquefied encapsulating matrix of step (a);
(c) emulsifying the mixture of step (b) with an aqueous medium comprising surfactant, said aqueous medium being at a temperature in the range of 30 - 200 degrees Centigrade; and (d) cooling the emulsion to room temperature, wherein the particles formed therefrom have diameters in the range of about 0.01 - 100 microns and comprise said matrix in combination with said UV-attenuating compound, said particles being solvent-free and dispersible within a dermatologically acceptable carrier.

19. The process of claim 18, wherein said temperature range of steps (a) and (c), individually, is 30 - 100 degrees Centigrade.

20. The process of claim 18, wherein said encapsulating matrix of step (a) comprises a substance selected from the group consisting of: natural wax and synthetic wax.

21. The process of claim 20, said natural wax comprising a material selected from the group consisting of alkyl wax ester, resin, vegetable matter components, clay-treated microcrystalline wax, oxidized hydrocarbon wax, natural and synthetic beeswax, auto-oxidized beeswax, candelilia, and carnauba.

22. The process of claim 20, said synthetic wax comprising a material selected from the group consisting of synthetic wax prepared by esterification of natural plant-derived fatty acids and alcohols, and paraffin wax.

23. The process of claim 20, wherein said UV-attenuating compound is selected from the group consisting of organic and inorganic UV-attenuators.

24. The process of claim 23, wherein said process further comprises the step of pretreating said inorganic UV-attenuator with a hydrophobic compound prior to mixing with said heated matrix.

25. The process of claim 23, wherein said process further comprises the step of mixing said organic sunscreen material with a solubilizing agent prior to incorporation into the matrix in an amount sufficient to reduce the potential of the UV-attenuator to recrystallize in the particle form.