WO2002007685A2 - Method of regulating hair growth using metal complexes of oxidized carbohydrates - Google Patents

Method of regulating hair growth using metal complexes of oxidized carbohydrates Download PDF

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Publication number
WO2002007685A2
WO2002007685A2 PCT/US2001/023424 US0123424W WO0207685A2 WO 2002007685 A2 WO2002007685 A2 WO 2002007685A2 US 0123424 W US0123424 W US 0123424W WO 0207685 A2 WO0207685 A2 WO 0207685A2
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Prior art keywords
acid
oxidized
zinc
hair
mixtures
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PCT/US2001/023424
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English (en)
French (fr)
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WO2002007685A8 (en
WO2002007685A3 (en
Inventor
John Michael Gardlik
Diana Severynse-Stevens
Bryan Gabriel Comstock
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The Procter & Gamble Company
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Priority to AU2001280779A priority Critical patent/AU2001280779A1/en
Publication of WO2002007685A2 publication Critical patent/WO2002007685A2/en
Publication of WO2002007685A3 publication Critical patent/WO2002007685A3/en
Publication of WO2002007685A8 publication Critical patent/WO2002007685A8/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27Zinc; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365Hydroxycarboxylic acids; Ketocarboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/58Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/731Cellulose; Quaternized cellulose derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/733Alginic acid; Salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/736Chitin; Chitosan; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73Polysaccharides
    • A61K8/737Galactomannans, e.g. guar; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/14Drugs for dermatological disorders for baldness or alopecia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q3/00Manicure or pedicure preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/58Metal complex; Coordination compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/006Antidandruff preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/02Preparations for cleaning the hair
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/06Preparations for styling the hair, e.g. by temporary shaping or colouring
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/12Preparations containing hair conditioners

Definitions

  • the present invention relates to a method of regulating hair growth comprising the administering, preferably topically, of compositions containing: (a) metal complexes of oxidized carbohydrates, but neither zinc gluconate nor manganese gluconate; and (b) a vehicle.
  • the hair of a mammal has always been recognized as an important symbol of beauty, strength, vitality and fashion, whether it be a lion's mane, a dog's shiny coat, or a human's locks.
  • the immense strength of the great Samson was ponderedly drained as Delilah severed his hair.
  • the Egyptian queen Cleopatra was known to immerse herself in luxuriant baths of milk and honey to revitalize her hair and skin.
  • post-medieval English and French courts those charged with administering the law were distinguished by wearing elaborate wigs.
  • the hair growth cycle can typically be divided into three main stages, namely: (a) the growth phase known as anagen, during which the hair follicle penetrates deep into the dermis with the cells of the bulb dividing rapidly and differentiating to form the hair; (b) the transitional stage known as catagen, which is heralded by the cessation of mitosis, and during which the follicle regresses upwards through the dermis and hair growth ceases; and (c) the resting stage known as telogen, in which the regressed follicle contains a small secondary germ with an underlying ball of tightly packed dermal papilla cells. The initiation of a new anagen phase is revealed by rapid proliferation in the germ, expansion of the dermal papilla and elaboration of basement membrane components.
  • Alopecia may be initiated or aggravated by many factors or conditions.
  • Alopecia may be hereditary, as in the case of male pattern baldness, or it may be due to disease, such as malnutrition, injury or insult, such as overdrying, bleaching, coloring, overbrushing, or treatment, such as chemotherapy, or it may occur in old age, or it may be due to physical, psychological or emotional stress, or still yet, it may be caused by hormonal imbalance, particularly during the advent of menopause.
  • the rate of hair growth may decrease, the rate of hair loss may increase, or the structure, including thickness of the hair may be altered. Also, hair may fall out gradually, or in patches.
  • DHT dihydrotestosterone
  • cytokines e.g. interleukin-1- ⁇ , interleukin-1- ⁇ , and tumor necrosis factor
  • cytokines e.g. interleukin-1- ⁇ , interleukin-1- ⁇ , and tumor necrosis factor
  • Antibodies produced by the immune system may also play a role in inhibiting hair growth. Accordingly, agents which inhibit inflammation, i.e. anti-inflammatories, may be used to regulate hair growth.
  • compounds that inhibit the immune system's ability to attach leukocytes to the follicle may be useful in regulating hair growth.
  • Various regimens are available for combating alopecia: (a) topical treatments for growing hair or for retarding the loss of hair (such as ROGAINE (RTM), available from Pharmacia & Upjohn); (b) oral treatments for growing hair or for retarding the loss of hair (such as PROPECIA (RTM), available from Merck Pharmaceuticals); (c) shampoos for making hair appear thicker and fuller (such as COUVRE (TM) Thickening Shampoo, available from Spencer Forrest, Inc.); (d) hair loss concealers for creating a cosmetic appearance that hair is not as thin as it really is (such as PROTHIK (TM) Spray, available from Aquila); (e) artificial hairpieces (such as toupees or weaves); (f) and surgical transplanting.
  • topical treatments for growing hair or for retarding the loss of hair such as ROGAINE (RTM), available from Pharmacia & Upjohn
  • oral treatments for growing hair or for retarding the loss of hair such as PROPECIA (RTM), available from Merck Pharmaceuticals
  • ROGAHNE active ingredient is minoxidil (6-(l- piperidinyl)-2,4-pyrimidinediamine 3-oxide)
  • minoxidil (6-(l- piperidinyl)-2,4-pyrimidinediamine 3-oxide)
  • the efficacy level is limited in those who do exhibit a response.
  • Many people find ROGAINE (RTM) to be expensive, and its side effects include itching, scaling and scalp irritation. Thickening shampoos and concealers do not actually increase hair growth or retard hair loss.
  • PROPECIA (finasteride) is a synthetic 4-azasteroid compound, that is a specific inhibitor of steroid Type II 5- ⁇ -reductase, an intracellular enzyme that converts the androgen testosterone into 5- ⁇ -dihydrotestosterone (DHT).
  • DHT 5- ⁇ -dihydrotestosterone
  • a reduction in DHT level is believed to correlate to a reduction in alopecia.
  • Finasteride is 4-azaandrost-l-ene-17-carboxamide,N-(l,l-dimethylethyl)- 3-oxo-,(5 ⁇ ,17 ⁇ )-, (see U.S. Pat. No. 5,670,643; EP 823,436; WO 97/15558; and WO 97/15564).
  • compositions containing certain metal complexes of oxidized carbohydrates which appeals to a larger number of consumers, at a reasonable price, which provides good results, with few, if any, undesirable side effects.
  • Applicants have found, surprisingly, that by applying compositions containing certain metal complexes of oxidized carbohydrates, the growth of hair in mammals can be regulated, and as such, alopecia can be combated. It is believed that zinc and other metals may regulate hair growth by (a) inhibiting activity of 5- ⁇ -reductase which converts testosterone to DHT, and (b) inhibiting DHT binding to the androgen receptor in the cytosol.
  • Zinc and other metals may also have an anti-inflammatory effect on hair follicles, which is believed to correlate to a reduction in alopecia.
  • certain metal complexes of oxidized carbohydrates can (a) dis upt DHT activity; and/or (b) stimulate the transition of follicles from the resting telogen phase into the active anagen phase and/or from earlier anagen phase to later anagen phase; and/or (c) retard the transition of follicles from anagen phase to catagen phase; and/or (d) may also have an anti-inflammatory effect on hair follicles.
  • the present invention relates to a method for regulating the growth of hair comprising administering to a mammal, an effective amount of a composition comprising: (a) from about 0.001% to about 99.9%, by weight, of at least one metal complex of an oxidized carbohydrate, wherein the metal complex of an oxidized carbohydrate is neither zinc gluconate nor manganese gluconate; and (b) from about 0.1% to about 99.999%, by weight, of a vehicle.
  • the present invention relates to a method for regulating the growth of hair.
  • these compositions comprise (a) at least one metal complex of an oxidized carbohydrate, but neither zinc gluconate nor manganese gluconate; and. (b) a vehicle.
  • These compositions when applied to a mammal, may disrupt DHT activity, stimulate the transition of follicles from the resting telogen phase into the active anagen phase, and may, in some cases, also have an anti-inflammatory effect. These characteristics are important to regulating the growth of hair.
  • compositions of the present invention can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any of the additional or optional ingredients, components or limitations described herein.
  • the components of the compositions of the present invention, including those which may optionally be added, as well as methods for preparation, and methods for use thereof, are described in detail below.
  • the term "hair” is meant to encompass all mammalian hair.
  • the hair is that of a human, however, animal hair, such as dog hair and cat hair are suitable.
  • animal hair such as dog hair and cat hair are suitable.
  • the hair whose growth is to be regulated is typically located upon the head, it is contemplated that the inventive method and compositions described herein may be applied to hair located anywhere on the body, including, eyebrows, mustaches, beards, the pubic area, and anywhere else the consumer prefers.
  • the terms "regulating hair growth,” “hair growth regulation,” and “regulating the growth of hair,” are meant to include: stimulating hair growth; stimulating hair thickening; preventing, reducing, arresting and/or retarding the loss of hair; preventing, reducing, arresting and/or retarding the thinning of hair; increasing the rate of hair growth; inducing the formation of a greater number of hair strands; increasing the diameter of the hair strand; lengthening the hair strand; changing the hair follicle from vellus follicle to terminal follicle; inducing the formation of vellus follicles; converting follicles from telogen to anagen phase (thereby increasing the overall ratio of anagen phase follicles relative to telogen phase follicles); advancing a follicle from an earlier stage of anagen to a later stage of anagen; reducing the conversion from anagen to catagen phase; treating alopecia; and any combination thereof.
  • vellus follicle means a hair follicle which produces a soft, short, and often colorless hair fiber.
  • the size of the vellus follicle is considerably smaller than the terminal hair follicle. In an adult, vellus follicles can be found on the forehead (i.e., receding hair line area) and bald scalp.
  • terminal follicle means a hair follicle which produces a coarse, long and often pigmented hair shaft.
  • the size of the terminal follicle is considerably larger and thicker in diameter and longer than the vellus follicle, hi an adult, terminal follicles can be found on the scalp, axilla and pubic areas.
  • anagen phase refers to the period in the hair follicle growth cycle wherein the follicle is actively growing and producing new hair.
  • telogen phase refers to the period in the hair growth cycle wherein the follicle is resting and not producing new hair.
  • oxidized carbohydrate is meant to be inclusive of acids derived from carbohydrates.
  • oxidized is meant to be inclusive of mono-, di-, and poly- oxidized.
  • carbohydrate is meant to be inclusive of mono-, di-, oligo-, and poly- saccharides.
  • safe and effective amount means an amount of an active ingredient high enough to modify the condition to be treated or to deliver the desired hair growth regulation benefit, but low enough to avoid serious side effects, at a reasonable benefit to risk ratio within the scope of sound medical judgment. What is a safe and effective amount of the active ingredient will vary with the specific active, the ability of the active to penetrate through the skin, hair, or relevant tissue of the digestive tract, the age, health condition, and skin, hair or digestive condition of the user, and other like factors.
  • compositions which comprise at least one metal complex of an oxidized carbohydrate and a vehicle.
  • Such compositions can be administered topically, orally or parenterally, preferably topically.
  • Such compositions can be in any form which delivers a sufficient amount of the metal complex of an oxidized carbohydrate to effectively regulate hair growth.
  • forms include, but are not limited to tablets, capsules, caplets, creams, gels, hydrogels, lotions, shampoos, rinses, tonics, sprays, ointments, mousses or pomade.
  • compositions herein are described in detail as follows.
  • many cosmetic ingredients have multiple functions in formulations and therefore may be included in several functional groupings. Accordingly, it should be understood that although the active ingredients useful herein are categorized by their therapeutic benefit or their postulated mode of action, some such ingredients can in some instances provide more than one cosmetic and/or therapeutic benefit or operate via more than one mode of action. Therefore, classifications herein are made for the sake of convenience and are not intended to limit the active ingredient to that particular application or applications listed. Also, where not stated otherwise, cosmetically and pharmaceutically acceptable salts of these active ingredients are useful herein. It is to be understood that the percentage weights of the composition components herein are expressed in terms of the total composition, and includes the composition in the form of intended use.
  • the method of the present invention utilizes compositions which comprise as an essential component, at least one metal complex of an oxidized carbohydrate in an amount which is sufficiently effective to regulate hair growth, wherein the at least one metal complex of an oxidized carbohydrate is neither zinc gluconate nor manganese gluconate.
  • zinc gluconate and manganese gluconate may optionally be included as additional ingredients.
  • an amount effective to regulate hair growth will range from about 0.001% to about 99.9%, by weight of the composition, preferably from about 0.001% to about 75%, more preferably from about 0.001% to about 50%, more preferably from about 0.001% to about 25%, more preferably from about 0.001% to about 15%.
  • the metal complexes of oxidized carbohydrates are believed to: (a) disrupt DHT activity; and/or (b) stimulate the transition of follicles from the resting telogen phase into the active anagen phase and/or from earlier anagen phase to later anagen phase; and/or (c) retard the transition of follicles from anagen phase to catagen phase; and/or (d) may also have an anti-inflammatory effect on hair follicles. These characteristics are important to regulating hair growth.
  • the metal complexes of oxidized carbohydrates are the result of an equilibrium reached between metal ions, and deprotonated carboxylic acids of carbohydrates, as shown, without regard to stereochemistry, in formulae (I) and (II), below. This equilibrium may be achieved during or before, preferably before, administration of the composition according to the method described herein.
  • the metal complex of an oxidized carbohydrate component of the compositions herein may be prepared by any suitable means.
  • metal-salt + carboxylic acid of carbohydrate yields metal complex of an oxidized carbohydrate and the conjugate acid of the metal's counter ion.
  • the pH of the resulting product may be adjusted using any suitable pH adjuster.
  • a non- limiting example of this preparation is: zinc sulfate + lactobionic acid yields zinc lactobionate and sulphuric acid, with the pH being adjusted to the desired level with sodium hydroxide.
  • Other non-limiting examples may be constructed using the metals, salts, oxidized carbohydrates, and pH adjusters described as suitable in the disclosure herein.
  • metal- salt preferably from about 0.5% to about 50%, preferably about 1% to about 25%, more preferably from about 3% to about 10%, of metal- salt will be added to typically about 0.5% to about 50%, preferably from about 1% to about 30%, more preferably from about 5% to about 25%, of carboxylic acid.
  • Suitable salts for use herein include, but are not limited to: the chlorides, sulfates, acetates, or oxides of sodium, lithium, potassium, silver, gold, zinc, copper, nickel, iron, chromium, calcium, magnesium, molybdenum, manganese, cobalt, palladium, platinum, and tin.
  • Non-limiting examples of preferred salts are zinc sulfate, zinc acetate, zinc oxide, cupric chloride, cupric sulfate, cupric acetate, and copper oxide.
  • the metal complex of an oxidized carbohydrate component of the compositions herein comprises metals. Such metals may be in an oxidation state or valence of 1 + .
  • Monovalent metals which are suitable for use herein include: lithium; silver; gold; sodium; and mixtures thereof. Preferred metals are sodium and lithium.
  • the metal complex of an oxidized carbohydrate component of the compositions herein comprises metals. Such metals may preferably be in an oxidation state or valence of 2 + .
  • Bivalent metals which are suitable for use herein include: zinc, copper, nickel, iron, chromium, calcium, magnesium, molybdenum, manganese, cobalt, palladium, platinum, tin, and mixtures thereof
  • Preferred metals include: zinc, copper, and mixtures thereof.
  • the metal complex of an oxidized carbohydrate component of the compositions herein comprise oxidized carbohydrates.
  • the oxidized carbohydrates may be used either in the dextro-rotary (D) or the levo-rotary (L) form. They may be substituted or un-substituted. When substituted, the oxidized carbohydrates useful herein may be amino-substituted, amido-substituted, phospho- substituted, or any mixture thereof. As described below, oxidized carbohydrates which are sulpho-substituted may optionally be included as additional ingredients.
  • oxidized carbohydrates for use herein include substituted or un-substituted monosaccharides, disaccharides, oligosaccharides, polysaccharides, and mixtures thereof.
  • Suitable oxidized carbohydrates for use herein include, but are not limited to: oxidized aldoses, oxidized ketoses, oxidized trioses, oxidized tetroses, oxidized pentoses, oxidized hexoses, and mixtures thereof.
  • oxidized monosaccharides for use herein include, but are not limited to: ribonic acid, ribulonic acid, arabinonic acid, xylonic acid, xylulonic acid, lyxonic acid, allonic acid, altronic acid, gluconic acid, mannonic acid, gulonic acid, idonic acid, galactonic acid, talonic acid, glucoheptonic acid, psiconic acid, fructonic acid, sorbonic acid, tagatonic acid, and mixtures thereof.
  • oxidized disaccharides for use herein include, but are not limited to: lactobionic acid, maltobionic acid, isomaltobionic acid, cellobionic acid, and mixtures thereof.
  • oxidized oligosaccharides for use herein include, but are not limited to: oxidized malto-oligosaccharide, oxidized cello-oligosaccharide, and mixtures thereof.
  • oxidized polysaccharides for use herein include, but are not limited to: oxidized cellulose; chitin; gum arabic; gum karaya; gum xanthan; oxidized gum guar; oxidized locust bean gum; oxidized agars; oxidized algins; oxidized gellan gum; and mixtures thereof.
  • preferred metal complexes of oxidized carbohydrates include, but are not limited to: lithium gluconate; copper gluconate; zinc galactonate; copper galactonate; zinc glucuronate; copper glucuronate; zinc galacturonate; copper galacturonate; zinc glucarate; copper glucarate; zinc galactarate; copper galactarate; zinc glucoheptonate; copper glucoheptonate; lithium lactobionate; sodium lactobionate; zinc lactobionate; copper lactobionate; lithium maltobionate; zinc maltobionate; copper maltobionate; lithium cellobionate; zinc cellobionate; copper cellobionate; and zinc alginate.
  • lithium lactobionate sodium lactobionate; zinc lactobionate; copper lactobionate; lithium maltobionate; zinc maltobionate; copper maltobionate; lithium cellobionate; zinc cellobionate; and copper cellobionate.
  • zinc lactobionate is particularly preferred.
  • zinc gluconate and manganese gluconate are preferred metal complexes of oxidized carbohydrates for use as additional optional ingredients.
  • Lithium gluconate can be represented by the following structure:
  • Zinc lactobionate can be represented by the following structure:
  • the metal complexes of oxidized carbohydrates of the present invention will have a solubility, at ambient conditions, in water of at least about 5%, by weight, preferably at least about 10%, more preferably at least about 40%, more preferably at least about 50%, more preferably at least about 60%.
  • solubility is a quantity that will dissolve in a given amount of solvent.
  • compositions which comprise as an essential component, a vehicle for the metal complex of an oxidized carbohydrate, in an amount sufficient to carry an effective amount of at least one metal complex of an oxidized carbohydrate onto or into the body in an amount which is sufficiently effective to regulate hair growth.
  • amount will range from about 0.1% to about 99.999%, by weight of the composition, preferably from about 25% to about 99.99%, more preferably from about 50% to about 99.9%, more preferably from about 75% to about 99%, more preferably from about 85% to about 99%.
  • the vehicle can comprise a solid, semi-solid or liquid cosmetically and/or physiologically acceptable vehicle, to enable the metal complex of an oxidized carbohydrate to be conveyed to the skin at an appropriate concentration.
  • pharmaceutically-acceptable means that drugs, medications or inert ingredients which the term describes are suitable for use in humans and lower animals without undue toxicity, incompatibility, instability, irritation, allergic response, and the like.
  • cosmetically acceptable means that ingredients which the term describes are suitable for use in contact with the skin or hair of humans and lower animals without undue toxicity, incompatibility, instability, irritation, allergic response and the like.
  • the nature of the vehicle will depend upon the method chosen for administration of the composition.
  • the vehicle can itself be inert or it can possess cosmetic or pharmaceutical benefits of its own.
  • such vehicles will act as diluents, dispersants, or solvents for the metal complex of an oxidized carbohydrates, which therefore ensure that they can be applied to and distributed evenly over the hair and/or scalp at an appropriate concentration.
  • the vehicle will preferably be one which can aid penetration of the metal complex of an oxidized carbohydrates into the skin to reach the immediate environment of the hair bulb.
  • such vehicles should be physically and chemically compatible with the essential components described herein, and should not otherwise unduly impair product stability, aesthetics or performance.
  • Vehicles suitable for use herein alone or in combination include: solvents; thickeners; propellants; powders; fillers; plasticizers; lubricants; and emollients and humectants.
  • the vehicle of the compositions of the present invention can comprise alone or in combination with other vehicle ingredients, solvents.
  • solvents suitable for use in the compositions herein are either water or are selected to be miscible with water and innocuous to the skin.
  • Solvents suitable for use herein include, but are not limited to: water; Ci to C 2 o mono- or poly- hydric alcohols and their ethers, preferred are C 2 to C 3 mono- and di- hydric alcohols, particularly ethanol, isopropanol, n-propanol, and butanol; propylene glycol; ethylene glycol monoethyl ether; glycerine; methylene chloride; diethylene glycol monobutyl ether; diethylene glycol monoethyl ether; dimethyl sulphoxide; dimethyl formamide; tetrahydrofuran; propylene glycol; and mixtures thereof.
  • Preferred solvents for use herein include: water, ethanol, isopropanol, propylene glycol, and mixtures thereof.
  • the solvent includes propylene glycol, it will typically contain it at a level of at least about 5%, by weight, preferably at least about 8%, ---ore preferably at least about 10%, and typically the level will range from about 5% to about 20%, preferably from about 8% to about 15%, more preferably from about 10% to about 15%. It is believed that the presence of at least about 5% propylene glycol may improve penetration, and thereby, efficacy, of the metal-oxidized carbohydrate complex. When topically applied, propylene glycol' s presence may also improve the appearance and/or the feel of the composition, on skin after drying.
  • the vehicle of the compositions of the present invention can comprise alone or in combination with other vehicle ingredients, thickening agents.
  • thickening agents when present, will be present at a level of from about 0.05% to about 20%, by weight of the composition, preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 5%.
  • the thickening function may be accomplished by a material also serving as a silicone or emollient. For instance, silicone gums in excess of 10 centistokes and esters such as glycerol stearate impart this dual functionality.
  • Thickening agents suitable for use in the compositions herein include, but are not limited to: oleic acid; cetyl alcohol; oleyl alcohol; sodium chloride; cetearyl alcohol; stearyl alcohol; synthetic thickeners such as those available under the tradenames ACULYN (RTM) and SALCARE (RTM) and ELFACOS (RTM), and those cross-linked polyacrylate materials available under the trademark Carbopol (RTM) from the B. F. Goodrich Company; and mixtures thereof.
  • thickeners for use herein are ACULYN (RTM) 22 steareth-20 methacrylate copolymer, ACULYN (RTM) 33 anionic acrylic copolymer, ACULYN (RTM) 44 polyurethane resin, and ACULYN (RTM) 46 hydrophobically modified nonionic polyol and others, which are available from ISP (International Specialty Products). Also suitable are the SALCARE (RTM) series of thickeners (SC80, 81, 91, 92, 95, 96 AST) available from Ciba Specialty Chemicals.
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • ELFACOS RTM
  • T212 PPG-14 Palmeth-60 Hexyl Dicarbamate PPG-14 Palmeth-60 Hexyl Dicarbamate.
  • Additional thickening agents suitable for use herein include: sodium alginate; gum arabic; cellulose derivatives, such as ethylcellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, and carboxymethylcellulose, or the sodium salt of carboxymethylcellulose; acrylic polymers, such as carboxyvinyl polymer; acrylic resins, such as EUDRAGIT (RTM) RL30D, available from Rohm Pharma GmbH Weiderstadt, West Germany; polyvinylpyrrolidone or other commercially available film-coating preparations, such as DRI-KLEAR (RTM), available form Crompton & Knowles Corp., Mahwah, New Jersey, USA, or OPADRY (RTM), available from Colorcon, West Point, Pennsylvania, USA.
  • cellulose derivatives such as ethylcellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropylmethylcellulose, and carboxymethylcellulose, or the sodium salt of carboxymethylcellulose
  • acrylic polymers such as carboxyvinyl
  • gums such as xanthan gum, guar gum, locust bean gum; carrageenan; gelatin; karaya; pectin; Biopolymer PS 87; clays, such as hectorites and bentonites; and mixtures thereof.
  • Additional thickeners suitable for use herein are those disclosed in: WO 99/37,047 (nonionic polyurethanes and/or cationic polymers); EP 0,875,237A2 (hydrophobically modified nonionic polyols and polyethoxylated urethane); WO 99/36,047 (polyurethane polymers and/or cationic conditioning agents); WO 98/03,150 (nonionic amphophilic polymers having at least one fatty chain); and U.S. Pat. No. 5,281,654 (mixture of polyurethanes), all of which descriptions are incorporated herein by reference.
  • the vehicle of the compositions of the present invention can comprise alone or in combination with other vehicle ingredients, propellants.
  • Propellants suitable for use herein include, but are not limited to: propane; butane; isobutane; dimethyl ether; carbon dioxide; nitrogen; nitrous oxide; and mixtures thereof.
  • the vehicle of the compositions of the present invention can comprise alone or in combination with other vehicle ingredients, powders.
  • Powders suitable for use herein include, but are not limited to: chalk; talc; fullers earth; kaolin; starch; gums; colloidal silicon dioxide; sodium polyacrylate; tetra alkyl and/or trialkyl aryl ammonium smectites; chemically modified magnesium aluminum silicate; organically modified montmorillonite clay; hydrated aluminum silicate; fumed silica; TiO 2 and Ti ⁇ 2 -coated mica, and mixtures thereof. 5. Fillers
  • the vehicle of the compositions of the present invention can comprise alone or in combination with other vehicle ingredients, fillers.
  • Fillers suitable for use herein include, but are not limited to: lactose, sucrose, maltodextrin, mannitol, starch, dicalcium phosphate and microcrystalline cellulose.
  • the vehicle of the compositions of the present invention can comprise alone or in combination with other vehicle ingredients, plasticizers.
  • Plasticizers suitable for use herein include, but are not limited to: polyethylene glycol; propylene glycol; dibutyl phthalate; castor oil; acetylated monoglycerides; triacetin; and mixtures thereof.
  • Lubricants The vehicle of the compositions of the present invention can comprise alone or in combination with other vehicle ingredients, lubricants.
  • Lubricants suitable for use herein include, but are not limited to: magnesium stearate; stearic acid; talc; and mixtures thereof.
  • Emollients and Humectants The vehicle of the compositions of the present invention can comprise alone or in combination with other vehicle ingredients, emollients and humectants. Some emollients and humectants which are useful as being all or part of the vehicle herein include, but are not limited to: esters; fatty alcohols and acids; polyols; hydrocarbons; non-volatile silicones; waxes; animal fats; vegetable oils; and mixtures thereof.
  • esters such class includes: Cl- C30 alcohol esters of C1-C30 carboxylic acids and of C2-C30 dicarboxylic acids, including straight and branched chain materials as well as aromatic derivatives can also be used herein.
  • esters such as monoglycerides of C1-C30 carboxylic acids, diglycerides of C1-C30 carboxylic acids, triglycerides of C1-C30 carboxylic acids, ethylene glycol monoesters of C1-C30 carboxylic acids, ethylene glycol diesters of C1-C30 carboxylic acids, propylene glycol monoesters of C1-C30 carboxylic acids, and propylene glycol diesters of C1-C30 carboxylic acids.
  • Straight chain, branched chain and aryl carboxylic acids are included herein.
  • propoxylated and ethoxylated derivatives of these materials are included herein.
  • esters useful herein include, but are not limited to: diisopropyl sebacate, diisopropyl adipate, isopropyl myristate, isopropyl palmitate, myristyl propionate, ethylene glycol distearate, 2-ethylhexyl palmitate, isodecyl neopentanoate, di-2-ethylhexyl maleate, cetyl palmitate, myristyl myristate, stearyl stearate, cetyl stearate, behenyl behenrate, dioctyl maleate, dioctyl sebacate, diisopropyl adipate, cetyl octanoate, diisopropyl dilinoleate, caprylic/capric triglyceride, PEG-6 caprylic/capric triglyceride, PEG-8 caprylic/capric triglycer
  • esters are derived from a sugar or polyol moiety and one or more carboxylic acid moieties. Depending on the constituent acid and sugar, these esters can be in either liquid or solid form at room temperature.
  • liquid esters include, but are not limited to: glucose tetraoleate, the glucose tetraesters of soybean oil fatty acids (unsaturated), the mannose tetraesters of mixed soybean oil fatty acids, the galactose tetraesters of oleic acid, the arabinose tetraesters of linoleic acid, xylose tetralinoleate, galactose pentaoleate, sorbitol tetraoleate, the sorbitol hexaesters of unsaturated soybean oil fatty acids, xylitol pentaoleate, sucrose tetraoleate, sucrose pentaoletate, sucrose hexaoleate, sucrose hepatoleate, sucrose octaoleate, and mixtures thereof.
  • solid esters include, but are not limited to: sorbitol hexaester in which the carboxylic acid ester moieties are palmitoleate and arachidate in a 1:2 molar ratio; the octaester of raffinose in which the carboxylic acid ester moieties are linoleate and behenate in a 1:3 molar ratio; the heptaester of maltose wherein the esterifying carboxylic acid moieties are sunflower seed oil fatty acids and lignocerate in a 3:4 molar ratio; the octaester of sucrose wherein the esterifying carboxylic acid moieties are oleate and behenate in a 2:6 molar ratio; and the octaester of sucrose wherein the esterifying carboxylic acid moieties are laurate, linoleate and behenate in a 1:3:4 molar ratio.
  • a preferred solid material is sucrose polyester in which the degree of esterification is 7-8, and in which the fatty acid moieties are C18 mono- and/or di-unsaturated and behenic, in a molar ratio of unsaturates:behenic of 1:7 to 3:5.
  • a particularly preferred solid sugar polyester is the octaester of sucrose in which there are about 7 behenic fatty acid moieties and about 1 oleic acid moiety in the molecule.
  • Other materials include cottonseed oil or soybean oil fatty acid esters of sucrose.
  • ester materials are further described in, U.S. Patent No. 2,831,854, U.S. Patent No. 4,005,196, to Jandacek, issued January 25, 1977; U.S. Patent No. 4,005,195, to Jandacek, issued January 25, 1977, U.S. Patent No. 5,306,516, to Letton et al., issued April 26, 1994; U.S. Patent No. 5,306,515, to Letton et al., issued April 26, 1994; U.S. Patent No. 5,305,514, to Letton et al, issued April 26, 1994; U.S. Patent No. 4,797,300, to Jandacek et al., issued January 10, 1989; U.S. Patent No.
  • Suitable fatty alcohols and acids for use herein include, but are not limited to those compounds having from 10 to 20 carbon atoms. Preferred are such compounds as cetyl, myristyl, palmitic and stearyl alcohols and acids.
  • polyols which may comprise all or part of the vehicle herein are linear and branched chain alkyl polyhydroxyl compounds.
  • Preferred polyols include propylene glycol, sugars having up to about 12 carbons atoms, sugar alcohols having up to about 12 carbon atoms, and mixtures thereof, glycerin, polypropylene glycols, polyethylene glycols, ethyl hexane diol, hexylene glycols, and mixtures thereof.
  • polyols useful herein include, but are not limited to: materials such as sucrose, fructose, glucose, eruthrose, erythritol, sorbitol, mannitol, glycerol, hexanetriol, propylene glycol, butylene glycol, hexylene glycol, and the like; polyethylene glycols such as
  • urea urea
  • guanidine glycolic acid and glycolate salts (e.g. ammonium and quaternary alkyl ammonium); lactic acid and lactate salts (e.g. ammonium and quaternary alkyl ammonium); cholesterol; and mixtures thereof.
  • aloe vera in any of its variety of forms (e.g., aloe vera gel), chitin, starch-grafted sodium polyacrylates such as SANWET (RTM) J-M-1000, J -1500, and IM-2500 (available from Celanese Superabsorbent Materials, Portsmouth, Virginia, USA); lactamide monoethanolamine; acetamide monoethanolamine; and mixtures thereof.
  • SANWET RTM
  • J-M-1000 J-M-1000
  • J -1500 J -1500
  • IM-2500 available from Celanese Superabsorbent Materials, Portsmouth, Virginia, USA
  • propoxylated glycerols described in U.S. Patent No. 4,976,953, to Orr et al., issued December 11, 1990, which is incorporated by reference herein in its entirety.
  • Suitable hydrocarbons for use in the vehicle herein are straight and branched chain hydrocarbons having from 7 to 40 carbon atoms.
  • Non-limiting examples include mineral oil, petrolatum, squalene, isoparaffins.
  • Mineral oil which is also known as petrolatum liquid, is a mixture of liquid hydrocarbons obtained from petroleum. See The Merck Index, Tenth Edition, Entry 7048, p. 1033 (1983) and International Cosmetic Ingredient Dictionary, Fifth Edition, vol. 1, p.415-417 (1993), which are incorporated by reference herein in their entirety.
  • Petrolatum which is also known as petroleum jelly, is a colloidal system of non-straight-chain solid hydrocarbons and high-boiling liquid hydrocarbons, in which most of the liquid hydrocarbons are held inside the micelles. See The Merck Index, Tenth Edition, Entry 7047, p. 1033 (1983); Schindler, Drug. Cosmet. bid., vol. 89, 36-37, 76, 78-80, 82 (1961); and International Cosmetic Ingredient Dictionary, Fifth Edition, vol. 1, p. 537 (1993), which are incorporated by reference herein in their entirety.
  • Non-volatile silicones such as polydialkylsiloxanes, polydiarylsiloxanes, and polyalkarylsiloxanes are also useful herein. These silicones are disclosed in U.S. Patent No. 5,069,897, to Orr, issued December 3, 1991, which is incorporated by reference herein in its entirety.
  • the polyalkylsiloxanes correspond to the general chemical formula R 3 SiO[R. 2 SiO] x SiR 3 wherein R is an alkyl group (preferably R is methyl or ethyl, more preferably methyl) and x is an integer up to about 500, chosen to achieve the desired molecular weight.
  • polyalkylsiloxanes include the polydimethylsiloxanes, which are also known as dimethicones, non-limiting examples of which include the VISCASIL (RTM) series sold by General Electric Company and the DOW CORNING (RTM) 200 series sold by Dow Corning Corporation.
  • Specific examples of polydimethylsiloxanes useful herein include DOW CORNING (RTM) 225 fluid having a viscosity of 10 centistokes and a boiling point greater than 200°C, and DOW CORNING (RTM) 200 fluids having viscosities of 50, 350, and 12,500 centistokes, respectively, and boiling points greater than 200°C.
  • trimethylsiloxysilicate which is a polymeric material corresponding to the general chemical formula [(CH 2 ) 3 SiOo.s] ⁇ [Si ⁇ 2]y, wherein x is an integer from about 1 to about 500 and y is an integer from about 1 to about 500.
  • a commercially available trimethylsiloxysilicate is sold as a mixture with dimethicone as DOW CORNING (RTM) 593 fluid.
  • dimethiconols which are hydroxy terminated dimethyl silicones.
  • RTM DOW CORNING
  • polyalkylaryl siloxanes with polymethylphenyl siloxanes having viscosities from about 15 to about 65 centistokes at 25 °C being preferred.
  • These materials are available, for example, as SF 1075 methylphenyl fluid (sold by General Electric Company) and 556 Cosmetic Grade phenyl trimethicone fluid (sold by Dow Corning Corporation).
  • Waxes which are useful in being all or part of the vehicle in the compositions herein include those set forth in CTFA Cosmetic Ingredient Handbook. Second Edition, 1992, pp. 535, which is herein incorporated by reference. Specific examples include beeswax, carnauba, candelilla wax, jojoba wax, lanolin wax, ozokerite, paraffin wax, and mixtures thereof.
  • Animal fats, vegetable oils and hydrogenated vegetable oils, and vegetable oil adducts are also potentially useful herein as all or part of the vehicle.
  • vegetable oils and hydrogenated vegetable oils include, but are not limited to: safflower oil, castor oil, coconut oil, cottonseed oil, menhaden oil, palm kernel oil, palm oil, peanut oil, soybean oil, rapeseed oil, linseed oil, rice bran oil, pine oil, sesame oil, sunflower seed oil, hydrogenated safflower oil, hydrogenated castor oil, hydrogenated coconut oil, hydrogenated cottonseed oil, hydrogenated menhaden oil, hydrogenated palm kernel oil, hydrogenated palm oil, hydrogenated peanut oil, hydrogenated soybean oil, hydrogenated rapeseed oil, hydrogenated linseed oil, hydrogenated rice bran oil, hydrogenated sesame oil, hydrogenated sunflower seed oil, and mixtures thereof.
  • Some preferred emollients and humectants for use herein include, but are not limited to: glycerine; sorbitol; sodium 2-pyrrolidone-5-carboxylate; soluble collagen; dibutyl phthalate; gelatin; stearyl alcohol; glyceryl monoricinoleate; glyceryl monostearate; propane-l,2-diol; butane-l,3-diol; mink oil; cetyl alcohol; isopropyl isostearate; stearic acid; isobutyl palmitate; isocetyl stearate; oleyl alcohol; isopropyl laurate; hexyl laurate; decyl oleate; octadecan-2-ol; isocetyl alcohol; cetyl palmitate; dimethylpolysiloxane; di-ra-butyl sebacate; isopropyl myristate; isoprop
  • compositions of the present invention may, in some embodiments, further comprise additional optional components known or otherwise effective for use in topically applied personal care products.
  • additional optional components known or otherwise effective for use in topically applied personal care products.
  • Surfactants, conditioning agents, cationic polymers, anti-dandruff actives, activity enhancers, penetration enhancers, suspending agents, non-steroidal anti-inflammatory drugs, topical anesthetics, and other optional components are described in detail below.
  • Any optional component(s) should be physically and chemically compatible with the essential components of the composition, and should not otherwise unduly impair product stability, aesthetics or performance.
  • Zinc gluconate and manganese gluconate are preferred metal complexes of oxidized carbohydrates for use as additional optional ingredients.
  • compositions utilized in the method of the present invention may, in some embodiments contain a surfactant suitable for application to the hair or skin, particularly when the compositions are to be applied topically, although surfactant may be used in any other form, adjusting the amount of surfactant present according to the desired effect for that particular form.
  • concentrations will range from about 5% to about 50%, by weight of the composition, preferably from about 8% to about 30%, more preferably from about 10% to about 25%, most preferably from about 12% to about 18%.
  • the surfactant is believed to provide cleaning and lather performance to the composition.
  • the anionic surfactant component can comprise an anionic detersive surfactant, a zwitterionic or an amphoteric detersive surfactant having an attached moiety that is anionic at the pH of the composition, or a combination thereof; preferably an anionic surfactant.
  • Suitable surfactants for use herein include, but are not limited to alkyl and alkyl ether sulfates, e.g. ammonium lauryl sulfate and ammonium laureth sulfate; olefin sulfonates; sarcosinates and sarcosine derivatives; alkoyl isethionates; soaps of fatty acids; and taurates; C 12 to 4 fatty acid mono-and di- ethanolamides, sucrose polyesters, polyhydroxy fatty acid amides, water soluble vegetable and animal-derived emollients, polyethylene glycol based polyethoxylated C9-C15 fatty alcohol nonionic surfactants containing an average of from about 5 to about 50 ethyleneoxy moieties per mole of surfactant, and amine oxides; betaines, sultaines, hydroxysultaines, alkyliminoacetates, iminodialkanoates, and aminoalkan
  • compositions herein may comprise from about 0.01% to about 30%, by weight of the composition, preferably from about 0.1% to about 20%, more preferably from about 0.1% to about 10%, most preferably from about 0.2% to about 6%, of a conditioning agent suitable for application to the hair or skin. It is believed that the conditioning agent provides improved conditioning benefits to the hair, particularly clean hair feel and wet rinse feel.
  • Suitable conditioning agents for use in the compositions herein are those conditioning agents characterized generally as silicones (e.g. silicone oils, cationic silicones, silicone gums, high refractive silicones, and silicone resins), organic conditioning oils (e.g. hydrocarbon oils, polyolefins, and fatty esters) or combinations thereof, or those conditioning agents which otherwise form liquid, dispersed, particles in the aqueous surfactant matrix herein.
  • silicones e.g. silicone oils, cationic silicones, silicone gums, high refractive silicones, and silicone resins
  • organic conditioning oils e.g. hydrocarbon oils, polyolefins, and fatty esters
  • the concentration of the conditioning agent in the composition should be sufficient to provide the desired conditioning benefits, and as will be apparent to one of ordinary skill in the art. Such concentration can vary with the conditioning agent, the conditioning performance desired, the average size of the conditioning agent particles, the type and concentration of other components, and other like factors.
  • Conditioning agents suitable for use herein include, but are not limited to: insoluble silicones comprising volatile silicone, non-volatile silicone, or combinations thereof; silicone oils, e.g. polyalkyl or polyaryl siloxanes; non-volatile polyalkylsiloxane fluids; alkylamino substituted silicones; insoluble silicone gums, such as those described in U.S. Pat. No. 4,152,416, Noll and Walter, Chemistry and Technology of Silicones, New York: Academic Press (1968), and in General Electric Silicone Rubber Product Data Sheets SE 30, SE 33, SE 54 and SE 76, all of whose descriptions are incorporated herein by reference; high refractive index silicones; silicone fluids disclosed in U.S. Pat. No.
  • the conditioning component of the compositions of the present invention may also comprise from about 0.05% to about 3%, by weight of the composition, preferably from about 0.08% to about 1.5%, more preferably from about 0.1% to about 1%, of at least one organic conditioning oil as the conditioning agent, either alone or in combination with other conditioning agents, such as the silicones (described above).
  • the conditioning oils may add shine and luster to the hair. Additionally, they may enhance dry combing and dry hair feel.
  • the organic conditioning oils suitable for use as the conditioning agent herein are preferably low viscosity, water insoluble, liquids selected from the hydrocarbon oils, polyolefins, fatty esters, and mixtures thereof.
  • the viscosity, as measured at 40°C, of such organic conditioning oils is preferably from about 1 centipoise to about 200 centipoise, more preferably from about 1 centipoise to about 100 centipoise, most preferably from about 2 centipoise to about 50 centipoise.
  • Suitable organic conditioning oils for use herein include, but are not limited to: hydrocarbon oils having at least about 10 carbon atoms; e.g. cyclic hydrocarbons; straight chain aliphatic hydrocarbons (saturated or unsaturated); branched chain aliphatic hydrocarbons (saturated or unsaturated); including polymers and mixtures thereof.
  • hydrocarbon oils having at least about 10 carbon atoms; e.g. cyclic hydrocarbons; straight chain aliphatic hydrocarbons (saturated or unsaturated); branched chain aliphatic hydrocarbons (saturated or unsaturated); including polymers and mixtures thereof.
  • liquid polyolefins more preferably liquid poly- ⁇ -olefins, most preferably hydrogenated liquid poly- ⁇ -olefins.
  • fatty esters typically having at least 10 carbon atoms, including esters with hydrocarbyl chains derived from fatty acids or alcohols (e.g. mono-esters, polyhydric alcohol esters, and di-
  • the hair growth regulating compositions of the present invention may comprise from about 0.005% to about 1.5%, by weight of the composition preferably from about 0.025% to about 0.1%, more preferably from about 0.05% to about 1%, more preferably from about 0.1% to about 0.5%, most preferably from about 0.1% to about 0.3%, of selected polyalkylene glycols suitable for application to the hair or skin.
  • selected polyalkylene glycols suitable for application to the hair or skin.
  • conditioning agents suitable for use herein are the series of conditioners available from International Specialty Chemicals, such as the GAFQUAT (RTM) series of quaternary copolymers, and the ARQUAD (RTM) series of quaternary ammonium salts, available from Akzo Nobel. Also suitable for use herein are those conditioning agents described in U.S. Pat. Nos. 4,529,586 (Clairol), 4,507,280 (Clairol), 4,663,158 (Clairol), 4,197,865 (L'Oreal), 4,217, 914 (L'Oreal), 4,381,919 (L'Oreal), and 4,422, 853 (L'Oreal), all of which descriptions are incorporated herein by reference.
  • compositions of the present invention may comprise from about 0.02% to about 5%, by weight of the composition, preferably from about 0.05% to about 3%, more preferably from about 0.1% to about 2%, most preferably from about 0.5% to about 1%, of at least one organic, cationic deposition and conditioning polymer suitable for application to the hair or skin.
  • Cationic polymers suitable for use herein include, but are not limited to: cationic polysaccharides; e.g. those described in the CTFA Cosmetic Ingredient Dictionary, 3d ed., edited by Estrin, Crosley, and Haynes, (The Cosmetic, Toiletry, and Fragrance Association, hie, Washington, D.C.
  • cationic cellulose derivatives and cationic starch derivatives cationic starch derivatives
  • cationic guar polymers copolymers of vinyl monomers, having cationic protonated amine or quaternary ammonium functionalities, reacted with water soluble monomers
  • vinyl pyrrolidone copolymers cationic modified proteins, e.g. lauryldimonium hydroxypropyl collagen; and mixtures thereof.
  • the hair growth regulating compositions of the present invention may, in some embodiments, comprise from about 0.1% to about 4%, by weight of the composition, preferably from about 0.1% to about 3%, most preferably from about 0.3% to about 2%, of an anti-dandruff active suitable for application to the hair or skin, which active may be particulate or soluble.
  • the anti- dandruff active provides the compositions with anti-microbial activity.
  • Suitable, non-limiting examples of anti-dandruff particulate actives include: pyridinethione salts, selenium sulfide, particulate sulfur, and mixtures thereof. Preferred are pyridinethione salts. Soluble anti-dandruff actives are described below along with other anti-microbials.
  • the hair growth regulating compositions of the present invention may in some embodiments, comprise pyridinethione anti-dandruff particulates, especially l-hydroxy-2-pyridinethione salts, are preferred particulate anti-dandruff agents for use.
  • concentration of pyridinethione anti- dandruff particulate typically ranges from about 0.1 % to about 4%, by weight of the composition, preferably from about 0.1% to about 3%, most preferably from about 0.3% to about 2%.
  • Preferred pyridinethione salts include those formed from heavy metals such as zinc, tin, cadmium, magnesium, aluminum and zirconium, preferably zinc, more preferably the zinc salt of l-hydroxy-2-pyridinethione (known as "zinc pyridinethione" or "ZPT"), most preferably 1- hydroxy-2-pyridinethione salts in platelet particle form, wherein the particles have an average size of up to about 20 ⁇ , preferably up to about 5 ⁇ , most preferably up to about 2.5 ⁇ . Salts formed from other cations, such as sodium, may also be suitable.
  • Pyridinethione anti-dandruff agents are described, for example, in U.S. Pat. No. 2,809,971; U.S. Pat. No.
  • ZPT may also function as an agent that regulates hair growth as an activity enhancer.
  • selenium sulfide and sulfur are also suitable for use herein.
  • compositions herein may also optionally comprise in some embodiments one or more activity enhancers.
  • activity enhancers can be chosen from a wide variety of molecules which can function in different ways to enhance the hair growth effects of a metal complex of an oxidized carbohydrate, of the present invention.
  • Some activity enhancers may have a direct effect on the regulation of hair growth themselves, others may work synergistically with the metal complexes of oxidized carbohydrates of the present invention to affect the regulation of hair growth.
  • Some activity enhancers can also function as vehicles for the metal complex of an oxidized carbohydrate, as noted above.
  • the activity enhancers described below while imparting some effect on the activity of the metal complexes of oxidized carbohydrates of the present invention, will continue to impart their commonly known effect to the compositions described herein, e.g. while an anti-microbial agent such as zinc pyrithione may affect the growth of hair, it will still impart a deleterious effect on microbes, such as those relating to dandruff.
  • the activity enhancers when present, are typically employed in the compositions herein at a level ranging from about 0.001% to about 15%, preferably from about 0.1% to about 10%, more preferably from about 0.5% to about 5% by weight of the composition. Non-limiting examples of activity enhancers are described below.
  • Vasodilators suitable for use herein include vasodilators, such as potassium channel agonists, including, for example, minoxidil and minoxidil derivatives, such as aminexil, and such as those described in U.S. Patent 3,382,247, U.S. Patent 5,756,092, issued May 26, 1998, U.S. Patent 5,772,990, issued June 30, 1998, U.S. Patent 5,760,043, issued June 2, 1998, U.S. Patent 328,914, issued July 12, 1994, U.S. Patent 5,466,694, issued November 14, 1995, 5,438,058, issued August 1, 1995, and U.S.
  • vasodilators such as potassium channel agonists, including, for example, minoxidil and minoxidil derivatives, such as aminexil, and such as those described in U.S. Patent 3,382,247, U.S. Patent 5,756,092, issued May 26, 1998, U.S. Patent 5,772,990, issued June 30, 1998, U.S. Patent 5,760,043, issued June 2, 1998
  • Optional activity enhancers suitable for use herein include anti-androgens.
  • suitable anti-androgens may include, but are not limited 5- ⁇ -reductase inhibitors such as finasteride and those described in U.S. Patent 5,516,779, issued May 14, 1996 (herein incorporated by reference) and in Nnane et al, Cancer Research 58. "Effects of Some Novel Inhibitors of C17,20-Lyase and 5 ⁇ -Reductase in Vitro and in Vivo and Their Potential Role in the Treatment of Prostate Cancer., as well as cyproterone acetate, azelaic acid and its derivatives and those compounds described in U.S.
  • Immunosuppressants such as 1) cyclosporin and cyclosporin analogs including those described in U.S. Provisional Patent Application No. 60/122,925, Fulmer et al., "Method of Treating Hair Loss Using Non- Immunosuppressive Compounds", filed March 5, 1999, herein incorporated by reference, and 2) FK506 analogs such as those described in U.S. Provisional Patent Application No. 60/102,449, Mclver et al., "Heterocyclic 2-Substituted Ketoamides", filed September 30, 1998, U.S.
  • Anti-microbial and Anti-fungal Actives suitable for use herein include anti-microbial and anti-fungal actives.
  • anti-microbial and anti-fungal actives useful herein include ⁇ -lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin, tetracycline, erythromycin, amikacin, 2,4,4'- trichloro-2'-hydroxy diphenyl ether, 3,4,4'-trichlorobanilide, phenoxyethanol, phenoxy propanol, phenoxyisopropanol, doxycycline, capreomycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, hexamidine isethionate, metronidazole, pentamidine, gentamicin, kanamycin, lineomycin, methacycline, methenamine, minocycline, ne
  • Anti-inflammatories can also be incorporated into the compositions herein as an optional activity enhancer.
  • suitable anti-inflammatories may include glucocorticoids such as hydrocortisone, mometasone furoate and prednisolone, nonsteroidal anti-inflammatories including cyclooxygenase or lipoxygenase inhibitors such as those described in U.S.
  • Patent 5,756,092 and benzydamine, salicylic acid those compounds described in EPA 0,770,399, published May 2, 1997, WO 94/06434, published March 31, 1994 and FR 2,268,523, published November 21, 1975, all of which are herein incorporated by reference, aspirin, ibuprofen, naproxen, indomethacin, piroxicam, flurbiprofen, meclofenamate sodium, ketoprofen, tenidap, tebufelone, and ketorolac.
  • Optional activity enhancers suitable for use herein include thyroid hormones and derivatives and analogs thereof.
  • suitable thyroid hormones for use herein may include triiodothyrionine.
  • thyroid hormone analogs which may be suitable for use herein include those described in U.S. Provisional Patent Application No. 60/136,996, Zhang et al., “Method of Treating Hair Loss", filed June 1, 1999, U.S. Provisional Patent Application No. 60/137,024, Zhang et al., "Method of Treating Hair Loss Using Biphenyl Compounds", filed June 1, 1999, U.S. Provisional Patent Application No.
  • Prostaglandin agonists can also be used as optional activity enhancers in the compositions herein.
  • suitable prostaglandins agonists or antagonists include latanoprost and those described in WO 98/33497, Johns-one, published August 6, 1998, WO 95/11003, Stjernschantz, published April 27, 1995, JP 97-100091, and Ueno, JP 96-134242, Nakamura.
  • Optional activity enhancers suitable for use herein include retinoids.
  • Suitable retinoids may include isotretinoin, acitretin, and tazarotene.
  • nicotinic acid and esters thereof particularly benzyl, nicotinate, methyl nicotinate and ethyl nicotinate;
  • Panthenol iii) alpha-1,4 esterified disaccharides as described by Choay S.A.
  • Still other activity enhancers suitable for use herein include flavinoids, ascomycin derivatives and analogs, histamine antagonists such as diphenhydramine hydrochloride, other triterpenes such as oleanolic acid and ursolic acid and those described in U.S. Patent 5,529,769, JP 10017431, WO 95/35103, U.S. Patent 5,468,888, JP 09067253, WO 92/09262, JP 62093215, U.S. Patent 5,631,282, U.S.
  • Patent 5,679,705, JP 08193094, saponins such as those described in EP 0,558,509 to Bonte et al, published September 8, 1993 and WO 97/01346 to Bonte et al, published January 16, 1997 (both of which are herein incorporated by reference in their entirety), proeoglycanase or glycosaminoglycanase inhibitors such as those described in U.S. Patents 5,015,470, issued May 14, 1991, U.S. Patent 5,300,284, issued April 5, 1994 and U.S.
  • Some preferred activity enhancers for use in the hair growth regulating compositions of the present invention include: zinc salts of carboxylic acids, minoxidil, finasteride, cyclosporin, ketoconazole, triclocarbon, triclosan, zinc pyrithione, itraconazole, hinokitiol, mipirocin, hydrocortisone, tenidap, triiodothyrionine, latanoprost, isotretinoin, acitretin, tazarotene, nicotinic acid, niacinamide, glycosaminoglycanase inhibitors, ethylenediaminetetraacetic acid, oleanolic acid, ursolic acid, interleukin-1 inhibitors, interleukin-6 inhibitors, interleukin-10 promotors, saponins, triterpenes, betulinic acid, betulonic acid, crataegolic acid, celastrol
  • compositions according to the invention may also optionally comprise one or more penetration enhancers, which may potentiate the benefit of the metal complex of an oxidized carbohydrate by improving its delivery through the stratum corneum to its site of action in the immediate environment of the hair follicle close to the hair bulb.
  • penetration enhancers may potentiate the benefit of the metal complex of an oxidized carbohydrate by improving its delivery through the stratum corneum to its site of action in the immediate environment of the hair follicle close to the hair bulb.
  • Non-limiting examples of penetration enhancers which may be used herein include, for example: 2-methyl propan-2-ol; propan-2-ol; l-propan-l,2-diol; ethyl-2-hydroxypropanoate; hexan-2,5- diol; POE(2) ethyl ether; di(2-hydroxypropyl) ether; pentan-2,4-diol; acetone; POE(2) methyl ether; 2-hydroxypropionic acid; 2-hydroxypropanoic acid; 2-hydroxyoctanoic acid; propan-1-ol; 1,4-dioxane; tetrahydrofuran; butan-l,4-diol; propylene glycol dipelargonate; polyoxypropylene 15 stearyl ether; octyl alcohol; POE ester of oleyl alcohol; oleyl alcohol; lauryl alcohol; dioctyl adipate; dicapryl a
  • Patent 5,015,470 issued May 14, 1991 and U.S. Patent 5,496,827, issued July 15, 1994 (both of which are herein incorporated in its entirety by reference), dimethylsulfonyl oxide (DMSO), octonol, niacinamide, and mixtures thereof.
  • DMSO dimethylsulfonyl oxide
  • octonol octonol
  • niacinamide niacinamide
  • the hair growth regulating compositions of the present invention may, in some embodiments, comprise from about 0.1% to about 10%, by weight of the composition, preferably from about 0.3% to about 5%, more preferably from about 0.3% to about 2.5%, of a suspending agent suitable for application to the hair or skin. It is believed that the suspending agent suspends water-insoluble, dispersed materials in the shampoo compositions.
  • suspending agents which may be suitably employed in the compositions herein include, but are not limited to: acyl derivatives, long chain amine oxides, xanthan gum, carboxyvinyl polymers; primary amines having a fatty alkyl moiety having at least about 16 carbon atoms (e.g.
  • palmitamine, and stearamine and secondary amines having two fatty alkyl moieties each having at least about 12 carbon atoms (e.g. dipalmitoylamine, and di-(hydrogenated taIlow)-amine).
  • cellulose ethers e.g., methylcellulose, hydroxybutyl methylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxyethyl ethylcellulose and hydroxyethylcellulose
  • guar gum polyvinyl alcohol, polyvinyl pyrrolidone, hydroxypropyl guar gum, starch and starch derivatives, and other thickeners, viscosity modifiers, gelling agents, and mixtures thereof.
  • a preferred viscosity modifier useful as a suspending agent is trihydroxystearin, (e.g. THIXIN (RTM) R, available from Rheox Company).
  • NSAIDS suitable for use herein include the following categories: propionic acid derivatives; acetic acid derivatives; fenamic acid derivatives; biphenylcarboxylic acid derivatives; and oxicams. All of these NSAIDS are fully described in U.S. Patent 4,985,459 to Sunshine et al., issued January 15, 1991, incorporated by reference herein in its entirety. Examples of useful
  • NSAIDS include acetyl salicylic acid, ibuprofen, naproxen, benoxaprofen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, tiaprofenic acid, fluprofen and bucloxic acid.
  • topical anesthetic drugs suitable for use herein include benzocaine, lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexyl- caine, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically acceptable salts thereof.
  • compositions described herein may be comprised of the following optional ingredients: conditioning agents selected from polydimethylsiloxane, polydiethylsiloxane, polymethylphenylsiloxane, amodimethicone, trimethylsilylamodimethicone, paraffin oil, mineral oil, polydecene, 1-decene homopolymer, C 8 -C ⁇ o triester of trimethylolpropane, polyethylene glycol, and mixtures thereof; cationic polymers selected from Polyquatemium 10, Polyquatemium 24, guar hydroxypropyltrimethylammonium chloride, Polyquatemium 16, and mixtures thereof; anti-dandruff actives selected from zinc pyrithione, selenium sulfide, sulfur, ketoconazole, climbazole, and mixtures thereof; activity enhancers selected from minoxidil, finasteride, cyclosporin, ketoconazole, triclocarbon, triclosan, zinc pyrithione,
  • the hair growth regulating compositions of the present invention may, in some embodiments, further comprise additional optional components known or otherwise effective for use in hair care or personal care products.
  • concentration of such optional ingredients generally ranges from zero to about 25%, more typically from about 0.05% to about 25%, even more typically from about 0.1% to about 15%, by weight of the composition.
  • Such optional components should also be physically and chemically compatible with the essential components described herein, and should not otherwise unduly impair product stability, aesthetics or performance.
  • Non limiting examples of optional components for use in the shampoo composition include antistatic agents (e.g. tricetyl methyl ammonium chloride), foam boosters (e.g. fatty ester (e.g. C 8 - C22) mono- and di (C1-C5, especially C1-C3) alkanol amides, preferably coconut monoethanolamide, coconut diethanolamide, and mixtures thereof), viscosity modifiers and thickeners (e.g. sodium chloride, sodium sulfate, and magnesium sulfate), pH adjusting agents (e.g.
  • antistatic agents e.g. tricetyl methyl ammonium chloride
  • foam boosters e.g. fatty ester (e.g. C 8 - C22) mono- and di (C1-C5, especially C1-C3) alkanol amides, preferably coconut monoethanolamide, coconut diethanolamide, and mixtures thereof
  • viscosity modifiers and thickeners e.g. sodium chloride,
  • anti-oxidants e.g. sodium sulphite, hydroquinone, sodium bisulphite, sodium metabisulphite and thyoglycolic acid, sodium dithionite, erythrobic acid and other mercaptans, which such anti-oxidants may be delivered using encapsulation techniques described in U.S. Pat. No.
  • the metal complexes of oxidized carbohydrates of the present invention may be synthesized using any conventional method. Some typical methods are: (a) multiple synthesis method, as described in "The Synthesis and Analysis of Copper (U) Carboxylates,” Yoder, et al., Journal of Chemical Education (1995), vol. 72, pages 267 et seq.; (b) bivalent metal oxide method, as described in “Complex Formation Between D-lactobionate and Bivalent Metal Ions,” Frutos, et al., Canadian Journal of Chemistry, (1977), vol.
  • compositions containing the metal complexes of oxidized carbohydrates of the present invention may be the form of a tablet, capsule, caplet, cream, gel, hydrogel, foam, mousse, liquid, solid, powder, tonic, rinse, shampoo, spray, paste, or other suitable form.
  • compositions according to the present invention can be packaged in a kit, as follows: one article of the kit comprises an individually packaged component containing at least one metal complex of an oxidized carbohydrate, while further kit articles could comprise one or more components for use in pre-treatment or post-treatment steps as part of a regimen for regulating hair growth regulating, for further enhancing hair growth performance, for creating special and individualized hair growth regulation effects, or for addressing specific needs of the consumer.
  • the method of the present invention involves the administration of the compositions described herein for regulating hair growth in mammals (e.g., humans and domestic animals). It is also contemplated that the compositions may be administered to the skin for achieving skin benefits, and to the finger nails or toe nails for nail growth benefits.
  • the compositions of the present invention can be administered topically, orally or parenterally.
  • a preferred method of using the present invention involves the topical application of the compositions described herein to the scalp, skin, and/or hair, more preferably to the scalp, skin, and/or hair where the scalp is already bald or balding.
  • the amount of the composition and the frequency of application to scalp, skin, and/or hair can vary widely, depending on the desired effect and/or personal needs.
  • compositions of the present invention can be also be used as a pre-treatment or post-treatment step to additional hair growth regulating processes taking place in order to further enhance hair growth performance or to create special and individualized hair growth regulation effects or to address specific needs of the consumer.
  • the topical compositions can be delivered the hair/scalp/skin from a variety of delivery devices.
  • the compositions can be incorporated into a medicated cleansing pad.
  • these pads comprise form about 50% to about 75% of a substrate and from about 25% to about 50% of a liquid composition deliverable from the substrate.
  • Suitable pads are described, for example, in U.S. Patent 4,891,228; Thurman et al.; issued January 2, 1990; and U.S. Patent 4,891,227; Thaman et al.; issued January 2, 1990, both of which are incorporated by reference.
  • Topical compositions of the present invention can also be delivered via any conventional hair care products, including, but not limited to shampoos, conditioners, styling products or other leave-in or rinse-off products.
  • Examples 1-8 are non-limiting examples of topical compositions used in the method of the present invention:
  • Tween 20 1.0 — 0.20 ... — ... ... ... propylene glycol 10.0 8.0 15.0 20.0 25.0 15.0 10.0 dimethylisosorbide 18.0 19.0 ... 18.0 18.0 — ... —
  • Examples 1-8 may be prepared as follows: 1. Add the ethyl alcohol, if present, and water, if present, and polyquatemium 10, if present, into mixing container and mix for 1 to 2 hours.
  • Examples 9-17 are non-limiting examples of topical compositions used in the method of the present invention:
  • Tween 20 1.0 ... 0.20 ... ... — ... 1.0 propylene glycol 10.0 8.0 15.0 20.0 25.0 6.0 12.0 18.0 10.0 dimethylisosorbide 18.0 19.0 ... 18.0 18.0 ... ... ... 18.0
  • Examples 9-17 may be prepared in the same manner as Examples 1-8.
  • Examples 18 and 19 are non-limiting examples of tablet compositions which can be used in the method of the present invention: Ingredient Example 18 (me) Example 19 Cms)
  • Example 18 may be prepared as follows:
  • Example 19 may be prepared as follows:
  • Example 20 is a non-limiting example of a composition which can be injected subcutaneously according to the method of the present invention.
  • Ingredient Example 20 fm-/mL
  • Example 20 may be prepared as follows:
  • the zinc lactobionate is micronized in a jet mill and sterilized by exposing it to 2.5 Mrad of radiation from a cobalt 60 source.
  • the dibasic sodium phosphate, monobasic sodium phosphate, edetate disodium, and benzalkoniurn chloride are dissolved in 9 liters of water for injection in a standard mixing tank.
  • the solution is filtered through a 0.22 micron filter to achieve sterilization.
  • the zinc lactobionate is added and mixed for 30 minutes under agitation. 5.
  • the suspension is aseptically filled into 3 mL flint glass vials, stoppered and sealed on standard filling equipment.
  • Examples 21 to 25 are non-limiting examples of shampoo compositions which embody the present invention.
  • Examples 21 to 25 may be prepared according to any conventional method for making shampoos.
  • Examples 26 to 30 are non-limiting examples of products prepared processes, which embody the present invention.
  • Examples 26 to 30 may be prepared as follows:
  • the resulting formulation will contain from about 0.001% to about 99.9%, by weight, of at least one metal complex of an oxidized carbohydrate, as desired.

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