EP3703651A1 - Multi-factor hair growth formulation

EP3703651A1 - Multi-factor hair growth formulation - Google Patents Multi-factor hair growth formulation

Info

Publication number EP3703651A1 EP3703651A1 EP18804839.1A EP18804839A EP3703651A1 EP 3703651 A1 EP3703651 A1 EP 3703651A1 EP 18804839 A EP18804839 A EP 18804839A EP 3703651 A1 EP3703651 A1 EP 3703651A1 Authority EP European Patent Office Prior art keywords skin surface applying formulation polypeptide synthetic peptides Prior art date 2017-11-03 Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.) Granted Application number EP18804839.1A Other languages German (de) French (fr) Other versions EP3703651B1 (en Inventor James Bartholomeusz Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.) Skinqri LLC Original Assignee Skinqri LLC Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.) 2017-11-03 Filing date 2018-11-02 Publication date 2020-09-09 2018-11-02 Application filed by Skinqri LLC filed Critical Skinqri LLC 2020-09-09 Publication of EP3703651A1 publication Critical patent/EP3703651A1/en 2024-09-25 Application granted granted Critical 2024-09-25 Publication of EP3703651B1 publication Critical patent/EP3703651B1/en Status Active legal-status Critical Current 2038-11-02 Anticipated expiration legal-status Critical

Links

Espacenet EPO GPI EP Register Global Dossier Discuss

Classifications

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K38/00—Medicinal preparations containing peptides

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells A61K35/14—Blood; Artificial blood A61K35/16—Blood plasma; Blood serum

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K38/00—Medicinal preparations containing peptides A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans A61K38/18—Growth factors; Growth regulators

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K8/00—Cosmetics or similar toiletry preparations A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K9/00—Medicinal preparations characterised by special physical form A61K9/0012—Galenical forms characterised by the site of application A61K9/0014—Skin, i.e. galenical aspects of topical compositions

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K9/00—Medicinal preparations characterised by special physical form A61K9/10—Dispersions; Emulsions A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K9/00—Medicinal preparations characterised by special physical form A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/51—Nanocapsules; Nanoparticles

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS A61P17/00—Drugs for dermatological disorders

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS A61P17/00—Drugs for dermatological disorders A61P17/04—Antipruritics

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS A61Q5/00—Preparations for care of the hair

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS A61Q7/00—Preparations for affecting hair growth

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

A—HUMAN NECESSITIES A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients A61K2800/59—Mixtures

Definitions

the present invention relates generally to a method and formulation for promoting hair growth and, more particularly, to a synergistic blend of oligiopeptides and growth factors selected to address differing stages of the human hair growth cycle, as well as methods of using such blends to promote hair growth. Hair loss prevention has been a topic of considerable interest. Numerous methods and compounds have been suggested to prevent loss of hair and/or to promote the growth of new hair. These approaches include medications such as finasteride (sold under the brand name Propecia) and minoxidil (sold as Rogaine), as well as individual oligopeptides or growth factors which, on an individual basis, are alleged to prevent hair loss and/or promote hair regeneration and growth. medications such as finasteride (sold under the brand name Propecia) and minoxidil (sold as Rogaine) individual oligopeptides or growth factors which, on an individual basis, are alleged to prevent hair loss and/or promote hair regeneration and growth. United States Patents 7,750,115; 7,560,428; 7,404,498; 7,241,731; and 7,095,569 disclose a variety of peptides, peptidic conjugates, and growth factor proteins that are individually alleged to promote hair growth and/or treat hair loss conditions such as alopecia. a number of pending patent publications describe peptides and other compositions in this regard, such as United States Patent Publication 2016/0199498; 2016/0199282; 2015/0272860; 2015/0265516; 2014/0069452; 2013/0011356; 2012/0065131 ; 2012/0054034; 2012/0039837; 2012/0021029; and 201 1/081802. Additional methods and other delivery systems are also described. the methods, the prescriptions, and/or oligopeptides appear to approach the question as a simple, single mechanism. the efficacy of these documents is implicitly or explicitly premised on the discovery that a single compound or method is more effective than previously known approaches. the current invention improves over previously disclosed formulations by considering the context of the hair growth cycle. In this manner, the inventors were able to utilize a combination of different items which provides an overall synergistic effect that vastly improves the efficacy of the hair growth treatment, particularly when coupled with specific means of introducing the serum containing that formulation to the scalp. One aspect of the invention contemplates a method for promoting hair growth. It includes any combination of the following features: o in group 2 protein rich plasma (PRP), human growth hormone (Hgh), vasoactive endothelial growth factor (VEFG), insulin-like growth factor (IGF); PRP protein rich plasma Hgh human growth hormone VEFG vasoactive endothelial growth factor IGF insulin-like growth factor EGF epidermal growth factor KGF keratin growth factor VIP vasoactive intestinal polypeptide topically applying the formulation to a skin surface of a subject, wherein the topically applying promotes uptake of the formulation into the skin surface but without ingestion or uptake of the formulation into the subject's bloodstream; wherein at least Hgh is selected from group 2 and at least VIP and EGF are selected from group 3; topically applying the formulation includes at least one of mechanical delivery means and energetic delivery means; the mechanical delivery means are selected from diliation of pores in the skin surface through use of a diliating or vaso-diliating agent, applying positive pressure to pores in the skin surface, applying negative pressure to pores in the skin surface, and puncturing the skin surface with one or more needles; the energetic delivery means are selected from iontophoresis, applying ultrasonic energy to the skin surface, applying visible light to the skin surface, applying radio waves to the skin surface, and creating temporary, fractional injuries in the skin surface with laser light; • wherein at least one of the synthetic peptides is individually encapsulated within at least one of lipids and nanoliposomes to create encapsulated particles; topically applying the formulation includes creating temporary, fractional injuries in the skin surface, said injuries having a width which accommodates the encapsulated particles; the width of the injuries is between 100 and 500 microns and wherein a depth of the injury is proximate to and no greater than a level of hair roots beneath the skin surface; formulation also contains at least one selected from group 4; a topical mixture of active ingredients for promoting all stages during an anagenic phase of human growth is described. the mixture includes sh-oligopeptide-1, sh-polypeptide-7, and sh-polypeptide-71. topical mixture may consist essentially of any combination of the following features: the encapsulating material is a nanoliposome combination of synthetic peptides also includes sh-polypeptide-2 and sh-polypeptide-9 and wherein an amount of sh-polypeptide-71 in the combination of synthetic peptides is comparatively lowest and an amount of sh-oligopeptide-1 in the combination of synthetic peptides is comparatively greatest; combination of synthetic peptides also includes sh-polypeptide-1 and sh-polypeptide-9 and wherein an amount of sh-oligopeptide-1 in the combination of synthetic peptides is comparatively lowest and an amount of sh-polypeptide-71 in the combination of synthetic peptides is comparatively greatest; sh-polypeptide-7, sh- oligopeptide-4, sh-polypeptide-1, sh-polypeptide-9, and sh-polypeptide-11 are provided in an approximately equal amounts that are between the amount of sh-oligopeptide-1 and the amount sh-polypeptide-71; the inactive components include at least one solvent, a surfactant, an antioxidant, a masking agent, and a smoothing agent; the solvents are pentylene glycol and water the surfactant is polysorbate the antioxidant is ascorbyl glucoside the chelator is disodium ethylenediaminetetaacetic acid the smoothing agent is niacinamide inactive components consist essentially of pentylene glycol, water, polysorbate, ascorbyl glucoside, disodium ethylenediaminetetraacetic acid, niancinamide, panethenol, and arginine. a method of preparing at least some of the aforementioned aspects of topical mixtures is also contemplated. This method may include any combination of the following: Methods for promoting hair growth are also contemplated in some aspects of the invention. these methods may include any combination of the following: applying the mixture includes at least one of mechanical delivery means and energetic delivery means; the mechanical delivery means are selected from diliation of pores in the skin surface through use of a diliating or vaso-diliating agent, applying positive pressure to pores in the skin surface, applying negative pressure to pores in the skin surface, and puncturing the skin surface with one or more needles; the energetic delivery means are selected from iontophoresis, applying ultrasonic energy to the skin surface, applying visible light to the skin surface, applying radio waves to the skin surface, and creating temporary, fractional injuries in the skin surface with laser light; the width of the injuries is between 100 and 500 microns and wherein a depth of the injury is proximate to and no greater than a level of hair roots beneath the skin surface. Figure 1 is a cross sectional side view illustration of a human hair follicle. Hair shaft S extends into the subject's skin connecting to hair root R. Root R comprises hair bulb B and hair matrix/papilla M. Bulge located stem cells B, derivative stem cell populations D, and transient amplifying cells TA are located proximate to these structures, while arrows 1 indicate the modifying influence of adjacent mesenchyme. the words “example” and “exemplary” mean an instance, or illustration. the words “example” or “exemplary” do not indicate a key or preferred aspect or embodiment. the word “or” is intended to be inclusive rather an exclusive, unless context suggests otherwise. the phrase “A employs B or C,” includes any inclusive permutation (e.g., A employs B; A employs C; or A employs both B and C). the articles “a” and “an” are generally intended to mean “one or more” unless context suggest otherwise. Both protein rich plasma (PRP) and human adipose-derived stem cell media contain some of the growth factors inherent to the prior art methods and compounds mentioned above. However, the inventors have discovered, since specific growth factors are more important than others in relation to hair growth, using only a single type growth factor and/or a fixed concentration of the mix of factors found in PRP and/or adipose-derived factors is not desirable. the inventive method focuses on a holistic range of growth factors specifically selected for aspects of hair growth, as well as a number of means to promote uptake of serums containing such formulations. the invention is distrinct from disci ousres that coincidentally identify a single growth factor (e.g., as pertinent in the context of wound healing or other uses not immediately associated with hair growth) and/or a method of promoting uptake that is not necessarily associated with the aims of this invention. a hair follicle generally illustrated in Figure 1— has a three phase life cycle. the anagen phase refers to actual growth, with the root dividing and adding structure and length to the hair shaft itself. the catagen phase is a transitional period from growth to rest, with blood supply being cut off from the cells that normally produce new hair. the final phase, the telogen phase results in dead hair that may be lost/shed from the scalp. the inventors Rather than focus on the broad anagen phase (which can last several years), the inventors identified four additional stages of that phase: 1) hair follicle induction; 2) hair follicle formation via stem cell proliferation; 3) growth of the hair shaft itself; and 4) microcirculation. these additional stages rather than generically referring to overall hair growth in the anagen phase— the inventors were able to identify and optimize specific growth factors and synthetic peptides that improve and influence hair growth. each hair will independently follow this cycle, such that a substantial portion of the individual hairs will be actively growing in a variety of these phases at any given time. inventive hair growth methods and formulations achieve improved results in comparison to prior art solutions wherein only a single growth factor or a single stage the hair growth phase is contemplated. topical application means the spray or serum (or whatever form the mixtures of compounds described herein may take) is applied to the surface of the skin without entering the bloodstream or otherwise being ingested by other organs or tissue. physical application may be by way of direct physical contact. This contact can include deliberate, fractional injuries and/or physical manipulation/movement of the skin and pores to facilitate penetration of the formulation down to hair root itself. These manipulations or injuries can be characterized as mechanical or energetic in nature. While each will be discussed separately below, it may be possible to incorporate a combination of these techniques to further improve the uptake of the formulation and, ultimately, the efficacy of the treatment/ application. Diliation may include vasodilating compounds or negative pressure vacuums which effectively open pores and/or create voids in the skin so as to allow the formulation to come into closer proximity with the hair root. pressure methods include the application of positive pressure so as to force the formulation into and through the skin, with vibration and massage of exposed skin being examples. Puncture methods contemplate the use of small needles (e.g., 32 gauge needles create 300 micron openings) or puncturing apparatus that to create a plurality of temporary openings. Energetic methods may rely on electrical current, sonic energy, and/or electromagnetic radiation. galvanic current e.g., iontophoresis Ultrasonic energy, lasers, visible light (e.g., red light), or radio waves (or other non-visible light) are also possibilities. some of these additional possibilities create openings in the top layer of the skin by way of fractional injury, while others create a temporary physiological response and/or mimic vibration and direct positive pressure (similar to the mechanical methods noted above) to accomplish the same effects. these energetic means may be used in combination with positive pressure to work the formulation into the skin. the openings or voids created by any of the delivery methods above should be between about 100 to 500 microns wide so as to accommodate the nanolipsome encapsulated particles described below. It may be possible to rely on even larger openings (e.g., less than 1000 microns, less than 750 microns, less than 600 microns, less than 500 microns, etc.), although consideration should be given to the comfort of the patient. the minimum size of the openings can be dictate by the size of the encapsulated particle (e.g., at least 100 microns, at least 200 microns, at least 250 microns, at least 300 microns, etc.). the depth of the openings does not need to penetrate the epidermis and, instead, should be calibrated to be in proximity with the hair roots. Notably, there is no need to have the formulation enter the bloodstream, such that the delivery methods are effectively intra-dermal and do not cause permanent injury or result in significant bleeding. the components of the formulation can be individually encapsulated and then mixed as part of the formlation processes contemplated below, although it may also be possible to create the entire formulation and then encapsulate that mixture. Additionally or alternatively, only selected components could be encapsulated. the active ingredients e.g., the synthetic peptides and growth factors identified below the inactive components could be provided in solution, serum, powder, slurry/suspension, or some other form. follistatin Wnt 7a aFGF acidic fibroblast growth factor bFGF basic fibroblast growth factor growth factors around the now-induced follicle unit in stage 2 up to four separate growth factors could be significant. These factors relate to wound healing and may include PRP, as well as human growth hormone (Hgh) and vascular or vasoactive endothelial growth factor (VEFG). Additionally, insulin-like growth factor (IGF) could be useful in this stage. PRP human growth hormone Hgh human growth hormone VEFG vascular or vasoactive endothelial growth factor IGF insulin-like growth factor EGF epidermal growth factor KGF keratin growth factor VIP vasoactive intestinal polypeptide stage 4 a combination of growth factors, skin proteins, and manual/mechanical massage prove to be useful. neo-vascularization and/or angiogenesis is desired at or around the follicle during this stage. the active compound most useful for these purposes is thymosin beta 4. these compounds may be individually or collectively coated or encapsulated in bio-compatible coatings to further facilitate delivery. the encapsulation reduces the formulation to an optimal, consistent size (relative to the "particle" formed by the encapsulation material) that is compatible with the selected delivery method. the formulation (or some or all of the individual components of the formulation) is coated and encapsulated with an appropriately biocompatible material so as to impart a particle size that is less than the needle size (e.g., particle size of 200 microns with 32-gauge needles having an outer diameter of approximately 300 microns), thereby allowing the encapsulated formulation to penetrate the top layer of skin and, ultimately, come into closer proximity to the hair root itself. an appropriately biocompatible material e.g., particle size of 200 microns with 32-gauge needles having an outer diameter of approximately 300 microns composition incorporates a plurality of different oligopeptides and polypeptides. the formulation may also include a number of inactive components, including water, glycerol, lecithin, polysorbate 60, sodium citrate, citric acid, and/or phenoxyethanol. Table 1 Basic hair rowth romotion ormulation. a second embodiment is provided in Table 2. This formulation should remain refrigerated, preferably between 2° and 8° C. the inactives may include glycerin (@ 2.0 w/w%), lecithin (@ 1.0 w/w%), Polysorbate 60 (@ 0.300 w/w%), sodium citrate (@ 0.150 w/w%), and citric acid (@ 0.020 w/w%). glycerin @ 2.0 w/w%) lecithin @ 1.0 w/w%) Polysorbate 60 @ 0.300 w/w%) sodium citrate @ 0.150 w/w%) citric acid @ 0.020 w/w% mass percentages in Table 2 are relative, so as to allow for easy scaling. any value within the range is contemplated, and three equally spaced intervals (in addition to the upper and lower limits) are specifically disclosed herein for each item (e.g., if the range disclosed is 0.00 to 1.00, this disclosure expressly includes at least 0.00, 0.25, 0.50, 0.750, and 1.00). a third embodiment is provided in Table 3a. homogenization should be employed by slow addition and mild mixing of the compounds to avoid foaming. Alcohols should be minimized, as they may negatively impact the stability of certain active ingredients. Less than 10 w/w% of ethanol is preferred. this table expressly discloses three equally spaced intervals in addition to these upper and lower limits for each line item. Table 3a Basic hair rowth romotion ormulation. sequence group A is slowly mixed and heated to 50°C. Group B compounds are then added, again with good mixing. the resulting mixture is allowed to cool to at least 40°C (and more preferably less than 35°C), at which point group C is added with good mixing. a cross linked polyacrylic acid polymer may also be employed. Water used herein should preferably be distilled and/or deionized. Table 3b discloses yet another formulation that is appropriate for mixing at room temperature. Each of the hair conditioning components should be added slowly and under sufficiently controlled mixing so as to avoid the formation of foam. Each may be pre-mixed with comparable amounts of water, glycerin, lechtin, polysorbate 60, sodium citrate, citric acid, and/or phenoxyethanol (for the purposes identified above). Any value within the range is contemplated, and three equally spaced intervals (in addition to the upper and lower limits) are specifically disclosed herein for each item. the invention may encompass selecting the proteins, peptides, and/or growth factors (or their functional equivalents) to address each of the stages identified by the inventors. a synergistic and heretofore unrealized level of efficacy can be attained in the promotion of hair growth. any of the embodiments contemplated above can be encapsulated. the encapsulating material(s) should be bio-compatible material and capable of eventually releasing the encapsulated material. Lipids, liposomes, and proteins, and particularly nanoliposomes, are useful in this regard. Non-limiting example of such encapsulating materials can be found in United States Patents 7,951,396 and 8,846,61 1, which are both incorporated by reference herein. the active components are individually encapsulated and then mix them at the desired proportions noted above, although it may be possible to encapsulate the final formulation in its entirety. non- limiting exemplary embodiments may include at least three separate formulations where, in a first example, component A is 0.1%, component B is 2.0%, and component C is 0.2%, while in a second example is component A at 0.1%, component B at 1.0%, and component C at 0.2% and a third example is component A at 0.5%, component B at 1.0%, and component C at 0.6%, etc.).

Landscapes

Health & Medical Sciences (AREA) Life Sciences & Earth Sciences (AREA) Animal Behavior & Ethology (AREA) General Health & Medical Sciences (AREA) Public Health (AREA) Veterinary Medicine (AREA) Chemical & Material Sciences (AREA) Medicinal Chemistry (AREA) Pharmacology & Pharmacy (AREA) Epidemiology (AREA) Engineering & Computer Science (AREA) Bioinformatics & Cheminformatics (AREA) Immunology (AREA) Proteomics, Peptides & Aminoacids (AREA) Gastroenterology & Hepatology (AREA) Zoology (AREA) Endocrinology (AREA) Dermatology (AREA) Vascular Medicine (AREA) General Chemical & Material Sciences (AREA) Organic Chemistry (AREA) Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA) Chemical Kinetics & Catalysis (AREA) Birds (AREA) Cell Biology (AREA) Hematology (AREA) Biomedical Technology (AREA) Diabetes (AREA) Molecular Biology (AREA) Dispersion Chemistry (AREA) Developmental Biology & Embryology (AREA) Biotechnology (AREA) Virology (AREA) Physics & Mathematics (AREA) Nanotechnology (AREA) Optics & Photonics (AREA) Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA) Cosmetics (AREA)

Abstract

A synergistic, multi-factor hair growth formulation and its method of use are described. A plurality of synthetic peptides and proteins are selected to maximize efficacy at discrete stages of the anagenic growth phase of a hair follicle, and these compounds may be further coated to promote uptake into the skin and/or hair root. The formulation itself is topical, so as to allow for direct, selective application alone or in combination with mechanical or energetic delivery techniques.

Description

TITLE

MULTI-FACTOR HAIR GROWTH FORMULATION

TECHNICAL FIELD

[0001] The present invention relates generally to a method and formulation for promoting hair growth and, more particularly, to a synergistic blend of oligiopeptides and growth factors selected to address differing stages of the human hair growth cycle, as well as methods of using such blends to promote hair growth.

BACKGROUND

[0002] Hair loss prevention has been a topic of considerable interest. Numerous methods and compounds have been suggested to prevent loss of hair and/or to promote the growth of new hair. These approaches include medications such as finasteride (sold under the brand name Propecia) and minoxidil (sold as Rogaine), as well as individual oligopeptides or growth factors which, on an individual basis, are alleged to prevent hair loss and/or promote hair regeneration and growth.

[0003] United States Patents 7,750,115; 7,560,428; 7,404,498; 7,241,731; and 7,095,569 disclose a variety of peptides, peptidic conjugates, and growth factor proteins that are individually alleged to promote hair growth and/or treat hair loss conditions such as alopecia. In the same manner, a number of pending patent publications describe peptides and other compositions in this regard, such as United States Patent Publication 2016/0199498; 2016/0199282; 2015/0272860; 2015/0265516; 2014/0069452; 2013/0011356; 2012/0065131 ; 2012/0054034; 2012/0039837; 2012/0021029; and 201 1/081802. Additional methods and other delivery systems are also described.

[0004] In each instance, the methods, the prescriptions, and/or oligopeptides appear to approach the question as a simple, single mechanism. In some instances, the efficacy of these documents is implicitly or explicitly premised on the discovery that a single compound or method is more effective than previously known approaches.

SUMMARY

[0005] The current invention improves over previously disclosed formulations by considering the context of the hair growth cycle. In this manner, the inventors were able to utilize a combination of different items which provides an overall synergistic effect that vastly improves the efficacy of the hair growth treatment, particularly when coupled with specific means of introducing the serum containing that formulation to the scalp.

[0006] By considering the question from the perspective of hair damage mechanisms, a multi-factored composition was identified to treat the anagenic phase, the progenitor cells associated with hair follicle, and stimulation of hair of the hair bulge. Additionally, compounds and methods which assist and improve upon underlying blood circulation within the scalp can be included to further enhance the efficacy of the final composition, including mechanical or energetic means.

[0007] One aspect of the invention contemplates a method for promoting hair growth. It includes any combination of the following features:

• creating a formulation from a plurality of synthetic peptides and growth factors associated with anagenic phase hair growth, including at least one selected from group 2 and at least one selected from group 3, selected from: o in group 1 : follistatin (Wnt 7a), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF);

o in group 2: protein rich plasma (PRP), human growth hormone (Hgh), vasoactive endothelial growth factor (VEFG), insulin-like growth factor (IGF);

o in group 3: epidermal growth factor (EGF), keratin growth factor (KGF), vasoactive intestinal polypeptide (VIP); and

o in group 4: thymosin beta 4;

topically applying the formulation to a skin surface of a subject, wherein the topically applying promotes uptake of the formulation into the skin surface but without ingestion or uptake of the formulation into the subject's bloodstream; wherein at least Hgh is selected from group 2 and at least VIP and EGF are selected from group 3;

wherein the topically applying the formulation includes at least one of mechanical delivery means and energetic delivery means;

wherein the mechanical delivery means are selected from diliation of pores in the skin surface through use of a diliating or vaso-diliating agent, applying positive pressure to pores in the skin surface, applying negative pressure to pores in the skin surface, and puncturing the skin surface with one or more needles;

wherein the energetic delivery means are selected from iontophoresis, applying ultrasonic energy to the skin surface, applying visible light to the skin surface, applying radio waves to the skin surface, and creating temporary, fractional injuries in the skin surface with laser light; • wherein at least one of the synthetic peptides is individually encapsulated within at least one of lipids and nanoliposomes to create encapsulated particles;

• wherein the topically applying the formulation includes creating temporary, fractional injuries in the skin surface, said injuries having a width which accommodates the encapsulated particles;

• wherein the width of the injuries is between 100 and 500 microns and wherein a depth of the injury is proximate to and no greater than a level of hair roots beneath the skin surface;

• wherein the formulation also contains at least one selected from group 4; and

• wherein the formulation also contains at least one selected from group 1

[0008] In another aspect, a topical mixture of active ingredients for promoting all stages during an anagenic phase of human growth is described. The mixture includes sh-oligopeptide-1, sh-polypeptide-7, and sh-polypeptide-71.

[0009] In a separate aspect, the topical mixture may consist essentially of any combination of the following features:

• a combination of synthetic peptides including sh-oligopeptide-1, sh- oligopeptide-4, sh-polypeptide-7, sh-polypeptide-1 1, and sh-polypeptide-71 ;

• inactive components including an encapsulating material;

• wherein the encapsulating material is a nanoliposome;

• wherein at least one of the synthetic peptides is individually encapsulated as particles having a size between 100 and 500 microns;

• wherein the combination of synthetic peptides also includes sh-polypeptide-2 and sh-polypeptide-9 and wherein an amount of sh-polypeptide-71 in the combination of synthetic peptides is comparatively lowest and an amount of sh-oligopeptide-1 in the combination of synthetic peptides is comparatively greatest;

• wherein the combination of synthetic peptides also includes sh-polypeptide-1 and sh-polypeptide-9 and wherein an amount of sh-oligopeptide-1 in the combination of synthetic peptides is comparatively lowest and an amount of sh-polypeptide-71 in the combination of synthetic peptides is comparatively greatest;

• wherein, in the combination of synthetic peptides, sh-polypeptide-7, sh- oligopeptide-4, sh-polypeptide-1, sh-polypeptide-9, and sh-polypeptide-11 are provided in an approximately equal amounts that are between the amount of sh-oligopeptide-1 and the amount sh-polypeptide-71;

• wherein the combination of synthetic peptides also includes sh-polypeptide-1;

• wherein the inactive components include at least one solvent, a surfactant, an antioxidant, a masking agent, and a smoothing agent;

• wherein the solvents are pentylene glycol and water, the surfactant is polysorbate, the antioxidant is ascorbyl glucoside, the chelator is disodium ethylenediaminetetaacetic acid, the smoothing agent is niacinamide; and

• wherein the inactive components consist essentially of pentylene glycol, water, polysorbate, ascorbyl glucoside, disodium ethylenediaminetetraacetic acid, niancinamide, panethenol, and arginine.

[0010] A method of preparing at least some of the aforementioned aspects of topical mixtures is also contemplated. This method may include any combination of the following:

• mixing the inactive components into a solvent to create a solution;

• heating the solution to 50°C; • allowing the solution to cool to less than 40°C and then mixing the combination of synthetic peptides into the solution; and

• wherein the combination of synthetic peptides are mixed into the solution when the solution is at approximately 35°C.

[0011] Methods for promoting hair growth are also contemplated in some aspects of the invention. Here, these methods may include any combination of the following:

• creating any topical mixture encompassed by the disclosure of paragraph 9 above;

• applying the topical mixture to a skin surface of a subject, wherein the topically applying promotes uptake of the formulation into the skin surface but without ingestion or uptake of the formulation into the subject's bloodstream;

• wherein the applying the mixture includes at least one of mechanical delivery means and energetic delivery means;

• wherein the mechanical delivery means are selected from diliation of pores in the skin surface through use of a diliating or vaso-diliating agent, applying positive pressure to pores in the skin surface, applying negative pressure to pores in the skin surface, and puncturing the skin surface with one or more needles;

• wherein the energetic delivery means are selected from iontophoresis, applying ultrasonic energy to the skin surface, applying visible light to the skin surface, applying radio waves to the skin surface, and creating temporary, fractional injuries in the skin surface with laser light;

• prior to applying the mixture, individually encapsulating at least one of the synthetic peptides within at least one of lipids and nanoliposomes to create encapsulated particles; • wherein the applying the mixture includes creating temporary, fractional injuries in the skin surface, said injuries having a width which accommodates the encapsulated particles; and

• wherein the width of the injuries is between 100 and 500 microns and wherein a depth of the injury is proximate to and no greater than a level of hair roots beneath the skin surface.

[0012] Specific reference is made to the appended claims, drawings, and description below, all of which disclose elements of the invention. While specific embodiments are identified, it will be understood that elements from one described aspect may be combined with those from a separately identified aspect. In the same manner, a person of ordinary skill will have the requisite understanding of common processes, components, and methods, and this description is intended to encompass and disclose such common aspects even if they are not expressly identified herein.

DESCRIPTION OF THE DRAWINGS

[0013] Operation of the invention may be better understood by reference to the detailed description taken in connection with the following illustrations. These appended drawings form part of this specification, and any written information in the drawings should be treated as part of this disclosure. In the same manner, the relative positioning and relationship of the components as shown in these drawings, as well as their function, shape, dimensions, and appearance, may all further inform certain aspects of the invention as if fully rewritten herein.

[0014] In the drawings:

[0015] Figure 1 is a cross sectional side view illustration of a human hair follicle. Hair shaft S extends into the subject's skin connecting to hair root R. Root R comprises hair bulb B and hair matrix/papilla M. Bulge located stem cells B, derivative stem cell populations D, and transient amplifying cells TA are located proximate to these structures, while arrows 1 indicate the modifying influence of adjacent mesenchyme.

DETAILED DESCRIPTION

[0016] Reference will now be made in detail to exemplary embodiments of the present invention, examples of which are illustrated in the accompanying drawings. It is to be understood that other embodiments may be utilized and structural and functional changes may be made without departing from the respective scope of the invention. As such, the following description is presented by way of illustration only and should not limit in any way the various alternatives and modifications that may be made to the illustrated embodiments and still be within the spirit and scope of the invention.

[0017] As used herein, the words "example" and "exemplary" mean an instance, or illustration. The words "example" or "exemplary" do not indicate a key or preferred aspect or embodiment. The word "or" is intended to be inclusive rather an exclusive, unless context suggests otherwise. As an example, the phrase "A employs B or C," includes any inclusive permutation (e.g., A employs B; A employs C; or A employs both B and C). As another matter, the articles "a" and "an" are generally intended to mean "one or more" unless context suggest otherwise.

[0018] Both protein rich plasma (PRP) and human adipose-derived stem cell media contain some of the growth factors inherent to the prior art methods and compounds mentioned above. However, the inventors have discovered, since specific growth factors are more important than others in relation to hair growth, using only a single type growth factor and/or a fixed concentration of the mix of factors found in PRP and/or adipose-derived factors is not desirable.

[0019] The inventive method focuses on a holistic range of growth factors specifically selected for aspects of hair growth, as well as a number of means to promote uptake of serums containing such formulations. As such, the invention is distrinct from disci ousres that coincidentally identify a single growth factor (e.g., as pertinent in the context of wound healing or other uses not immediately associated with hair growth) and/or a method of promoting uptake that is not necessarily associated with the aims of this invention.

[0020] First, the inventors considered the entirety of the hair growth cycle. Generally speaking, a hair follicle— generally illustrated in Figure 1— has a three phase life cycle. The anagen phase refers to actual growth, with the root dividing and adding structure and length to the hair shaft itself. The catagen phase is a transitional period from growth to rest, with blood supply being cut off from the cells that normally produce new hair. The final phase, the telogen phase, results in dead hair that may be lost/shed from the scalp.

[0021] Rather than focus on the broad anagen phase (which can last several years), the inventors identified four additional stages of that phase: 1) hair follicle induction; 2) hair follicle formation via stem cell proliferation; 3) growth of the hair shaft itself; and 4) microcirculation. By considering these additional stages— rather than generically referring to overall hair growth in the anagen phase— the inventors were able to identify and optimize specific growth factors and synthetic peptides that improve and influence hair growth. Notably, each hair will independently follow this cycle, such that a substantial portion of the individual hairs will be actively growing in a variety of these phases at any given time. Thus, by providing formulations that address all of the phases, rather than focusing on a single component to influence a single phase or stage, the inventive hair growth methods and formulations achieve improved results in comparison to prior art solutions wherein only a single growth factor or a single stage the hair growth phase is contemplated.

[0022] Additionally, instead of approaching the question of hair loss as one to be treated by orally ingested medication, the inventors deliberately selected an approach that considered topical application. In this manner, the treatment can be more selectively applied, either as a spray or serum. As used herein, it will be understood that topical application means the spray or serum (or whatever form the mixtures of compounds described herein may take) is applied to the surface of the skin without entering the bloodstream or otherwise being ingested by other organs or tissue.

[0023] In particular, physical application may be by way of direct physical contact. This contact can include deliberate, fractional injuries and/or physical manipulation/movement of the skin and pores to facilitate penetration of the formulation down to hair root itself. These manipulations or injuries can be characterized as mechanical or energetic in nature. While each will be discussed separately below, it may be possible to incorporate a combination of these techniques to further improve the uptake of the formulation and, ultimately, the efficacy of the treatment/ application.

[0024] With respect to mechanical methods, these can be subdivided into diliation, pressure, and puncture methods. Diliation may include vasodilating compounds or negative pressure vacuums which effectively open pores and/or create voids in the skin so as to allow the formulation to come into closer proximity with the hair root. In contrast, pressure methods include the application of positive pressure so as to force the formulation into and through the skin, with vibration and massage of exposed skin being examples. Puncture methods contemplate the use of small needles (e.g., 32 gauge needles create 300 micron openings) or puncturing apparatus that to create a plurality of temporary openings.

[0025] Energetic methods may rely on electrical current, sonic energy, and/or electromagnetic radiation. In partucliar, galvanic current (e.g., iontophoresis) can be applied to the skin open pores. Ultrasonic energy, lasers, visible light (e.g., red light), or radio waves (or other non-visible light) are also possibilities. Notably, some of these additional possibilities create openings in the top layer of the skin by way of fractional injury, while others create a temporary physiological response and/or mimic vibration and direct positive pressure (similar to the mechanical methods noted above) to accomplish the same effects. In each instance, these energetic means may be used in combination with positive pressure to work the formulation into the skin.

[0026] Preferably, the openings or voids created by any of the delivery methods above should be between about 100 to 500 microns wide so as to accommodate the nanolipsome encapsulated particles described below. It may be possible to rely on even larger openings (e.g., less than 1000 microns, less than 750 microns, less than 600 microns, less than 500 microns, etc.), although consideration should be given to the comfort of the patient. The minimum size of the openings can be dictate by the size of the encapsulated particle (e.g., at least 100 microns, at least 200 microns, at least 250 microns, at least 300 microns, etc.). The depth of the openings does not need to penetrate the epidermis and, instead, should be calibrated to be in proximity with the hair roots. Notably, there is no need to have the formulation enter the bloodstream, such that the delivery methods are effectively intra-dermal and do not cause permanent injury or result in significant bleeding. [0027] The components of the formulation can be individually encapsulated and then mixed as part of the formlation processes contemplated below, although it may also be possible to create the entire formulation and then encapsulate that mixture. Additionally or alternatively, only selected components could be encapsulated. For example, the active ingredients (e.g., the synthetic peptides and growth factors identified below) need to be encapsulated, while the inactive components could be provided in solution, serum, powder, slurry/suspension, or some other form.

[0028] With respect to the formulation itself, a plurality of synthetic peptides and growth factors were associated with each of the four anagenic stages identified above. In stage 1, follistatin (Wnt 7a) and/or acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) were identified as useful in facilitating the switch from catagen/telogenic phases back to the anagenic phase, as well as potentially helpful in promoting the induction of new follicular bulbs.

[0029] In order to increase growth factors around the now-induced follicle unit in stage 2, up to four separate growth factors could be significant. These factors relate to wound healing and may include PRP, as well as human growth hormone (Hgh) and vascular or vasoactive endothelial growth factor (VEFG). Additionally, insulin-like growth factor (IGF) could be useful in this stage.

[0030] Growth of the hair shaft itself in stage 3 may determine the density, length, and color of the resulting hair. Further, certain skin proteins may be expressed at this stage. As such, key active compounds include epidermal growth factor (EGF), keratin growth factor (KGF), and/or vasoactive intestinal polypeptide (VIP) are significant, particularly in connection with the bulge cells during the anagen phase.

[0031] Finally, in stage 4, a combination of growth factors, skin proteins, and manual/mechanical massage prove to be useful. In particular, neo-vascularization and/or angiogenesis is desired at or around the follicle during this stage. The active compound most useful for these purposes is thymosin beta 4.

[0032] As noted above, the use mechanical and/or energetic delivery methods, as well as massage/physical contact, may prove useful to enhance topical penetration and maintain healthy scalp circulation. Further, these compounds— and particularly some or all of the active ingredients— may be individually or collectively coated or encapsulated in bio-compatible coatings to further facilitate delivery. The encapsulation reduces the formulation to an optimal, consistent size (relative to the "particle" formed by the encapsulation material) that is compatible with the selected delivery method. For example, with respect to mechanical methods such as micro- puncturing, the formulation (or some or all of the individual components of the formulation) is coated and encapsulated with an appropriately biocompatible material so as to impart a particle size that is less than the needle size (e.g., particle size of 200 microns with 32-gauge needles having an outer diameter of approximately 300 microns), thereby allowing the encapsulated formulation to penetrate the top layer of skin and, ultimately, come into closer proximity to the hair root itself.

[0033] In terms of formulations that sufficiently accommodate the various phases and stages as described above, the inventors combined a series of peptides and growth factors that were previously only considered useful on an individual basis. Thus, table 1 below describes one embodiment of the invention. The composition incorporates a plurality of different oligopeptides and polypeptides. The formulation may also include a number of inactive components, including water, glycerol, lecithin, polysorbate 60, sodium citrate, citric acid, and/or phenoxyethanol. Table 1. Basic hair rowth romotion ormulation.

[0034] A second embodiment is provided in Table 2. This formulation should remain refrigerated, preferably between 2° and 8° C.

Table 2. Basic hair rowth romotion ormulation.

[0035] The inactives may include glycerin (@ 2.0 w/w%), lecithin (@ 1.0 w/w%), Polysorbate 60 (@ 0.300 w/w%), sodium citrate (@ 0.150 w/w%), and citric acid (@ 0.020 w/w%). However, other inactives may be used, so long as the substituted, added, or omitted substances fulfill substantially similar roles as the disclosed blend. Also, the mass percentages in Table 2 are relative, so as to allow for easy scaling. Notably, any value within the range is contemplated, and three equally spaced intervals (in addition to the upper and lower limits) are specifically disclosed herein for each item (e.g., if the range disclosed is 0.00 to 1.00, this disclosure expressly includes at least 0.00, 0.25, 0.50, 0.750, and 1.00).

[0036] A third embodiment is provided in Table 3a. When preparing this composition, homogenization should be employed by slow addition and mild mixing of the compounds to avoid foaming. Alcohols should be minimized, as they may negatively impact the stability of certain active ingredients. Less than 10 w/w% of ethanol is preferred. Here again, in addition to the specifically disclosed lower and upper values, this table expressly discloses three equally spaced intervals in addition to these upper and lower limits for each line item.

Table 3a. Basic hair rowth romotion ormulation.

*These compounds are provided at ~ 0.5 to 2 ppm with water, lecithin, sodium phosphate, pheoxyethanol, and disodium EDTA. The active protein should be at least 95% pure.

[0037] In certain embodiments, it may be possible to employ a specific sequence of heating and mixing to further improve the efficacy. The compounds associated with sequence group A are slowly mixed and heated to 50°C. Group B compounds are then added, again with good mixing. The resulting mixture is allowed to cool to at least 40°C (and more preferably less than 35°C), at which point group C is added with good mixing. A cross linked polyacrylic acid polymer may also be employed. Water used herein should preferably be distilled and/or deionized.

[0038] Table 3b discloses yet another formulation that is appropriate for mixing at room temperature. Each of the hair conditioning components should be added slowly and under sufficiently controlled mixing so as to avoid the formation of foam. Each may be pre-mixed with comparable amounts of water, glycerin, lechtin, polysorbate 60, sodium citrate, citric acid, and/or phenoxyethanol (for the purposes identified above). Any value within the range is contemplated, and three equally spaced intervals (in addition to the upper and lower limits) are specifically disclosed herein for each item.

Table 3b. Basic hair rowth ormulation

[0039] Thus, additional formulations based on the four stage approach described above are possible. In the most abstract form, the invention may encompass selecting the proteins, peptides, and/or growth factors (or their functional equivalents) to address each of the stages identified by the inventors. In this manner, a synergistic and heretofore unrealized level of efficacy can be attained in the promotion of hair growth. Further, given the topical application, it is possible to selectively apply the formulation to the areas desired to experience hair growth. In this manner, some of the shortcomings of oral medications or broad-based treatments can be diminished.

[0040] Any of the embodiments contemplated above can be encapsulated. The encapsulating material(s) should be bio-compatible material and capable of eventually releasing the encapsulated material. Lipids, liposomes, and proteins, and particularly nanoliposomes, are useful in this regard. Non-limiting example of such encapsulating materials can be found in United States Patents 7,951,396 and 8,846,61 1, which are both incorporated by reference herein. Preferably, the active components are individually encapsulated and then mix them at the desired proportions noted above, although it may be possible to encapsulate the final formulation in its entirety.

[0041] Although the present embodiments have been illustrated in the accompanying drawings and described in the foregoing detailed description, it is to be understood that the invention is not to be limited to just the embodiments disclosed, and numerous rearrangements, modifications and substitutions are also contemplated. The exemplary embodiment has been described with reference to the preferred embodiments, but further modifications and alterations encompass the preceding detailed description. These modifications and alterations also fall within the scope of the appended claims or the equivalents thereof.

[0042] Understanding that the formulations herein necessarily include multiple components and that each component is indicated as having a range of possible concentration values, contemplated embodiments encompass any combination of selected values for each disclosed range (e.g., if component A is provided at 0.1% to 0.5%; component B at 1.0% to 2.0%; and component C at 0.2% to 0.6%, then non- limiting exemplary embodiments may include at least three separate formulations where, in a first example, component A is 0.1%, component B is 2.0%, and component C is 0.2%, while in a second example is component A at 0.1%, component B at 1.0%, and component C at 0.2% and a third example is component A at 0.5%, component B at 1.0%, and component C at 0.6%, etc.).

Claims CLAIMS What is claimed is:

1. A method for promoting hair growth comprising:

creating a formulation from a plurality of synthetic peptides and growth factors associated with anagenic phase hair growth, including at least one selected from group 2 and at least one selected from group 3, selected from:

in group 1 : follistatin (Wnt 7a), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF);

in group 2: protein rich plasma (PRP), human growth hormone (Hgh), vasoactive endothelial growth factor (VEFG), insulin-like growth factor (IGF);

in group 3: epidermal growth factor (EGF), keratin growth factor

(KGF), vasoactive intestinal polypeptide (VIP); and in group 4: thymosin beta 4; and

2. The method according to claim 1 wherein at least Hgh is selected from group 2 and at least VIP and EGF are selected from group 3.

3. The method according to claim 2 wherein the topically applying the formulation includes at least one of mechanical delivery means and energetic delivery means.

4. The method according to claim 3 wherein the mechanical delivery means are selected from diliation of pores in the skin surface through use of a diliating or vaso- diliating agent, applying positive pressure to pores in the skin surface, applying negative pressure to pores in the skin surface, and puncturing the skin surface with one or more needles.

5. The method according to claim 3 wherein the energetic delivery means are selected from iontophoresis, applying ultrasonic energy to the skin surface, applying visible light to the skin surface, applying radio waves to the skin surface, and creating temporary, fractional injuries in the skin surface with laser light.

6. The method according to claim 2 wherein at least one of the synthetic peptides is individually encapsulated within at least one of lipids and nanoliposomes to create encapsulated particles.

7. The method according to claim 6 wherein the topically applying the formulation includes creating temporary, fractional injuries in the skin surface, said injuries having a width which accommodates the encapsulated particles.

8. The method according to claim 7 wherein the width of the injuries is between 100 and 500 microns and wherein a depth of the injury is proximate to and no greater than a level of hair roots beneath the skin surface.

9. The method according to any one of claims 1 , 2, 3, 4, 5, 6, 7, and 8 wherein the formulation also contains at least one selected from group 4.

10. The method according to any one of claims 1 , 2, 3, 4, 5, 6, 7, and 8 wherein the formulation also contains at least one selected from group 1.

11. A topical mixture of active ingredients for promoting all stages during an anagenic phase of human hair growth, the mixture comprising:

sh-oligopeptide-1 ;

sh-polypeptide-7; and

sh-polypeptide-71.

12. A topical mixture of active ingredients for promoting all stages during an anagenic phase of human hair growth, the mixture consisting essentially of:

a combination of synthetic peptides including sh-oligopeptide-1 , sh- oligopeptide-4, sh-polypeptide-7, sh-polypeptide-1 1, and sh-polypeptide-71 ; and inactive components.

13. The topical mixture according to claim 12 wherein the inactive components include an encapsulating material.

14. The topical mixture according to claim 13 wherein the encapsulating material is a nanoliposome.

15. The topical mixture according to claim 14 wherein at least one of the synthetic peptides is individually encapsulated as particles having a size between 100 and 500 microns.

16. The topical mixture according to any one of claims 12, 13, 14, and 15 wherein the combination of synthetic peptides also includes sh-polypeptide-2 and sh-polypeptide- 9 and wherein an amount of sh-polypeptide-71 in the combination of synthetic peptides is comparatively lowest and an amount of sh-oligopeptide-1 in the combination of synthetic peptides is comparatively greatest.

17. The topical mixture according to any one of claims 12, 13, 14, and 15 wherein the combination of synthetic peptides also includes sh-polypeptide-1 and sh-polypeptide- 9 and wherein an amount of sh-oligopeptide-1 in the combination of synthetic peptides is comparatively lowest and an amount of sh-polypeptide-71 in the combination of synthetic peptides is comparatively greatest.

18. The topical mixture according to claim 17 wherein, in the combination of synthetic peptides, sh-polypeptide-7, sh-oligopeptide-4, sh-polypeptide-1, sh- polypeptide-9, and sh-poly peptide- 11 are provided in an approximately equal amounts that are between the amount of sh-oligopeptide-1 and the amount sh-polypeptide-71.

19. The topical mixture according to any one of claims 12, 13, 14, and 15, wherein the combination of synthetic peptides also includes sh-poly peptide- 1.

20. The topical mixture according to claim 19 wherein the inactive components include at least one solvent, a surfactant, an antioxidant, a masking agent, and a smoothing agent.

21. The topical mixture according to claim 20 wherein the solvents are pentylene glycol and water, the surfactant is polysorbate, the antioxidant is ascorbyl glucoside, the chelator is disodium ethylenediaminetetaacetic acid, the smoothing agent is niacinamide.

22. The topical mixture according to claim 19 wherein the inactive components consist essentially of pentylene glycol, water, polysorbate, ascorbyl glucoside, disodium ethylenediaminetetraacetic acid, niancinamide, panethenol, and arginine.

23. A method of preparing the topical mixture of claim 20 comprising:

mixing the inactive components into a solvent to create a solution;

heating the solution to 50°C; and

allowing the solution to cool to less than 40°C and then mixing the combination of synthetic peptides into the solution.

24. The method according to claim 21 wherein the combination of synthetic peptides are mixed into the solution when the solution is at approximately 35°C.

25. A method for promoting hair growth comprising:

creating a topical mixture according to claim 19; and applying the topical mixture to a skin surface of a subject, wherein the topically applying promotes uptake of the formulation into the skin surface but without ingestion or uptake of the formulation into a subject's bloodstream.

26. The method according to claim 25 wherein the applying the mixture includes at least one of mechanical delivery means and energetic delivery means.

27. The method according to claim 26 wherein the mechanical delivery means are selected from diliation of pores in the skin surface through use of a diliating or vaso- diliating agent, applying positive pressure to pores in the skin surface, applying negative pressure to pores in the skin surface, and puncturing the skin surface with one or more needles.

28. The method according to claim 26 wherein the energetic delivery means are selected from iontophoresis, applying ultrasonic energy to the skin surface, applying visible light to the skin surface, applying radio waves to the skin surface, and creating temporary, fractional injuries in the skin surface with laser light.

29. The method according to claim 25 further comprising, prior to applying the mixture, individually encapsulating at least one of the synthetic peptides within at least one of lipids and nanoliposomes to create encapsulated particles.

30. The method according to claim 29 wherein the applying the mixture includes creating temporary, fractional injuries in the skin surface, said injuries having a width which accommodates the encapsulated particles.

31. The method according to claim 30 wherein the width of the injuries is between 100 and 500 microns and wherein a depth of the injury is proximate to and no greater than a level of hair roots beneath the skin surface.

32. A method for promoting hair growth comprising:

creating a topical mixture according to claim 17; and applying the topical mixture to a skin surface of a subject, wherein the topically applying promotes uptake of the formulation into the skin surface but without ingestion or uptake of the formulation into a subject's bloodstream.

33. The method according to claim 32 wherein the applying the mixture includes at least one of mechanical delivery means and energetic delivery means.

34. The method according to claim 33 wherein the mechanical delivery means are selected from diliation of pores in the skin surface through use of a diliating or vaso- diliating agent, applying positive pressure to pores in the skin surface, applying negative pressure to pores in the skin surface, and puncturing the skin surface with one or more needles.

35. The method according to claim 33 wherein the energetic delivery means are selected from iontophoresis, applying ultrasonic energy to the skin surface, applying visible light to the skin surface, applying radio waves to the skin surface, and creating temporary, fractional injuries in the skin surface with laser light.

36. The method according to claim 32 further comprising, prior to applying the mixture, individually encapsulating at least one of the synthetic peptides within at least one of lipids and nanoliposomes to create encapsulated particles.

37. The method according to claim 36 wherein the applying the mixture includes creating temporary, fractional injuries in the skin surface, said injuries having a width which accommodates the encapsulated particles.

38. The method according to claim 37 wherein the width of the injuries is between 100 and 500 microns and wherein a depth of the injury is proximate to and no greater than a level of hair roots beneath the skin surface.

39. A method for promoting hair growth comprising:

creating a topical mixture according to claim 16; and applying the topical mixture to a skin surface of a subject, wherein the topically applying promotes uptake of the formulation into the skin surface but without ingestion or uptake of the formulation into a subject's bloodstream.

40. The method according to claim 39 wherein the applying the mixture includes at least one of mechanical delivery means and energetic delivery means.

41. The method according to claim 40 wherein the mechanical delivery means are selected from diliation of pores in the skin surface through use of a diliating or vaso- diliating agent, applying positive pressure to pores in the skin surface, applying negative pressure to pores in the skin surface, and puncturing the skin surface with one or more needles.

42. The method according to claim 40 wherein the energetic delivery means are selected from iontophoresis, applying ultrasonic energy to the skin surface, applying visible light to the skin surface, applying radio waves to the skin surface, and creating temporary, fractional injuries in the skin surface with laser light.

43. The method according to claim 39 further comprising, prior to applying the mixture, individually encapsulating at least one of the synthetic peptides within at least one of lipids and nanoliposomes to create encapsulated particles.

44. The method according to claim 43 wherein the applying the mixture includes creating temporary, fractional injuries in the skin surface, said injuries having a width which accommodates the encapsulated particles.

45. The method according to claim 44 wherein the width of the injuries is between 100 and 500 microns and wherein a depth of the injury is proximate to and no greater than a level of hair roots beneath the skin surface. EP18804839.1A 2017-11-03 2018-11-02 Multi-factor hair growth formulation Active EP3703651B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title US201762581103P 2017-11-03 2017-11-03 PCT/US2018/058826 WO2019090008A1 (en) 2017-11-03 2018-11-02 Multi-factor hair growth formulation

Publications (2)

Publication Number Publication Date EP3703651A1 true EP3703651A1 (en) 2020-09-09 EP3703651B1 EP3703651B1 (en) 2024-09-25

Family

ID=64362715

Family Applications (1)

Application Number Title Priority Date Filing Date EP18804839.1A Active EP3703651B1 (en) 2017-11-03 2018-11-02 Multi-factor hair growth formulation

Country Status (6)

Country Link US (1) US10894074B2 (en) EP (1) EP3703651B1 (en) KR (2) KR20240154106A (en) DK (1) DK3703651T3 (en) ES (1) ES2998479T3 (en) WO (1) WO2019090008A1 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party Publication number Priority date Publication date Assignee Title KR102346391B1 (en) * 2020-01-28 2022-01-04 주식회사 라비오 Composition for strengthening hair root and hair EP4120996A4 (en) * 2020-03-19 2024-09-25 Skingen International Inc. SKIN CARE COMPOSITIONS CONTAINING 8 OR MORE RECOMBINANT HUMAN GROWTH FACTORS AND USE THEREOF TO REDUCE SIGNS OF AGING US12303470B2 (en) * 2021-06-03 2025-05-20 Skinqri, Llc Method and composition for selective treatment of androgen receptors KR102369387B1 (en) * 2021-09-10 2022-03-08 (주)한성이비지니스 Cosmetic Composition for prevention of depilation or improvement of hair growth KR102582633B1 (en) * 2023-02-08 2023-09-26 주식회사 바니스트 Cosmetic composition for skin regeneration and wrinkle improvement containing epidermal growth factor liposomes and growth factor complex

Family Cites Families (28)

* Cited by examiner, † Cited by third party Publication number Priority date Publication date Assignee Title JPH04224522A (en) * 1990-04-27 1992-08-13 Merck & Co Inc Therapeutic or prophylactic method for alopecia using composition containing fibroblast growth factor US7241731B2 (en) 2000-06-05 2007-07-10 Sumitomo Electric Industries, Ltd. Oligopeptides for promoting hair growth JPWO2004101610A1 (en) 2003-05-16 2006-10-26 住友電気工業株式会社 Oligopeptide WO2005095441A1 (en) 2004-03-31 2005-10-13 National Institute Of Advanced Industrial Science And Technology Epithelial cell growth promoter US7095569B2 (en) 2004-04-26 2006-08-22 Delphi Technologies, Inc. Lens system for a motor vehicle vision system US20060242024A1 (en) 2004-09-02 2006-10-26 Welcomemat Services, Inc. Business method for promoting goods and services of providers JP4504772B2 (en) 2004-09-27 2010-07-14 株式会社ニフコ Fuel tank refueling pipe DE102004063627A1 (en) 2004-12-27 2006-07-06 Henkel Kgaa Hair treatment preparations containing corneocyte proteins or polypeptides and silicone (s) MX2007010674A (en) 2005-03-03 2007-11-08 Revance Therapeutics Inc Compositions and methods for topical application and transdermal delivery of an oligopeptide. US20070224150A1 (en) * 2005-03-24 2007-09-27 Yongji Chung Growth factor for hair and skin treatment JP4970424B2 (en) 2005-03-28 2012-07-04 リゲロンアイエヌシー Method for producing nanoliposome surrounding protein and protein-enclosing nanoliposome KR100705981B1 (en) 2005-10-12 2007-04-10 주식회사 리제론 Hair loss prevention or hair growth promoting composition containing human growth hormone KR100802144B1 (en) * 2007-01-24 2008-02-14 (주)쉐르본 Hair loss prevention or composition for promoting hair growth US20080317733A1 (en) * 2007-06-20 2008-12-25 Nugene Inc. Cosmeceutical Compositions and Methods with Biologically Active Ingredients CN101990425B (en) 2008-04-08 2016-01-20 默克专利股份有限公司 Compositions comprising cyclic peptides and methods of use US8287845B2 (en) 2008-12-18 2012-10-16 E I Du Pont De Nemours And Company Hair-binding peptides CN102395598B (en) 2009-04-17 2014-07-30 利普泰股份公司 Peptides for the treatment and/or care of the skin and/or hair, and their use in cosmetic or pharmaceutical compositions US8221159B2 (en) 2009-09-25 2012-07-17 Thomas William Knepp Audio patchbay/breakout panel GB2485475A (en) * 2010-11-10 2012-05-16 Pangaea Lab Ltd Topical growth factor application using controlled and multiple wounding of the skin KR101321011B1 (en) * 2011-11-30 2013-10-23 주식회사 엘지생활건강 Composition for Improvement of Skin microrelief WO2013190567A2 (en) * 2012-06-19 2013-12-27 Shome Debraj Composition and method for an intradermal hair growth solution DE102012216296A1 (en) 2012-09-13 2014-03-13 Henkel Ag & Co. Kgaa Hair care preparations containing selected amino acids and / or selected oligopeptides and selected plant-based cationic surfactants DE102012222768A1 (en) 2012-12-11 2014-06-12 Henkel Ag & Co. Kgaa Hair care compositions containing selected and / or selected oligopeptides and / or selected cationic protein hydrolysates and silicones containing sugar structures WO2015023649A2 (en) 2013-08-12 2015-02-19 3M Innovative Properties Company Peptides for enhancing transdermal delivery DE102013219919A1 (en) 2013-10-01 2015-04-02 Henkel Ag & Co. Kgaa Upgraded hair products US9173921B1 (en) * 2015-03-23 2015-11-03 Jaehyun Lim Method of promoting hair growth by administration of bFGF KR101772574B1 (en) * 2015-07-14 2017-08-30 (주)피앤피바이오팜 A cosmetic composition for hair care comprising growth factors, highly stable basic fibroblast growth factor and noggin peptide to promote regeneration and growth of hair follicular cell KR102535575B1 (en) * 2016-02-26 2023-05-23 (주)피앤피바이오팜 A cosmetic composition for hair care comprising high stable Fibroblast Growth Factor-9 mutant

2018

2018-11-02 US US16/178,693 patent/US10894074B2/en active Active 2018-11-02 WO PCT/US2018/058826 patent/WO2019090008A1/en not_active Ceased 2018-11-02 EP EP18804839.1A patent/EP3703651B1/en active Active 2018-11-02 KR KR1020247034726A patent/KR20240154106A/en active Pending 2018-11-02 DK DK18804839.1T patent/DK3703651T3/en active 2018-11-02 KR KR1020207015997A patent/KR102760486B1/en active Active 2018-11-02 ES ES18804839T patent/ES2998479T3/en active Active

Also Published As

Publication number Publication date KR102760486B1 (en) 2025-02-04 KR20200104289A (en) 2020-09-03 KR20240154106A (en) 2024-10-24 US20190134142A1 (en) 2019-05-09 DK3703651T3 (en) 2024-11-04 ES2998479T3 (en) 2025-02-20 WO2019090008A1 (en) 2019-05-09 US10894074B2 (en) 2021-01-19 EP3703651B1 (en) 2024-09-25

Follow this recovery question

Related recovery notes

Explore More Research from MendStride

Continue Through the MendStride Archive

Discover Another MendStride Research Page

Browse Additional MendStride Insights

Open More Research from MendStride

Continue Reading on MendStride