WO2013167927A1

WO2013167927A1 - Formulation and method for treating hair loss

Info

Publication number: WO2013167927A1
Application number: PCT/IB2012/000923
Authority: WO
Inventors: Guillermo Alfredo DURAN
Original assignee: Biologix Hair Science Ltd.
Priority date: 2012-05-11
Filing date: 2012-05-11
Publication date: 2013-11-14

Abstract

An injectable composition or kit for treating hair loss includes biotin, minerals and oligo-elements, organic silicon, pentoxyfilline, and procaine hydrochloride. The minerals and oligo-elements include at least Boron (B), Sulfur (S). The composition can include a buffering agent, for example sodium bicarbonate, to maintain a desired pH, for example a pH between about 5.3 and 5.7. The compositions can be used to promote hair loss caused by alopecia areata, androgenic alopecia, frontal fibrosing alopecia and effluviums Additional minerals and oligo-elements can include Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), Zinc (Zn), Nickel (Ni), Vanadium (Va), Calcium (Ca), Magnesium (Mg), Potassium (K), Chlorine (CI), Lithium (Li), Iodine (I), or Copper (Cu) and combinations thereof. The composition can also include one or more of D-panthenol; triamcinolone; Serenoa repens; capsaicin; bimatoprost; lanatoprost; essential amino acids; follicusan; cell growth factors; stem cells; Astressin-B; Fullerenes (for example as a vehicle); Asiasari Radix extract; Ginseng extract; Cyoctol; and RU 58841.

Description

Formulation and Method For Treating Hair Loss

Field of the Invention

The present invention relates generally to a formulation and method for treating hair loss. More particularly the invention relates to an injectable composition to stop hair loss and promote hair re-growth.

Background

Baldness is seen in modern society as related to lack of attractiveness, sexual potency and aging. The syndrome that causes baldness is complex, multifactor and polygenic, and the psychological ramifications are equally complex.

"Alopecia" is the medical term for hair loss in humans - both male and female.

Alopecia can be caused by a number of factors and be manifested in a number of different ways. For example, androgenic alopecia, often known as male pattern baldness, typically begins in men above the temples and then affects the top of the head. Androgenic alopecia can often be the result of overproduction of dihydrotestosterone (DHT). The syndrome often results in a ring of hair that leaves the center of the scalp bald in the so-called "Hippocratic balding" pattern. Women experiencing androgenic alopecia, while balding, are not necessarily subjected to this particular pattern of hair loss but instead may undergo thinning across the entire scalp.

Alopecia areata is another condition which can manifest itself as hair loss in patches and, if not treated, can in time evolve into complete baldness. Alopecia areata can happen at any age and it often begins in childhood. It is an autoimmune disease, which means the body's immune system attacks its own hair follicles, rendering them inactive. A person's genetic makeup, combined with other factors, triggers this form of hair loss.

Another type of hair loss is effluviums, including telogen effluvium and anagen effluvium. Telogen effluvium is a form of nonscarring alopecia characterized by diffuse hair shedding. Telogen effluvium can be a reactive process caused by a metabolic or hormonal stress or by medications. Anagen effluvium is the loss of anagen or growth-phase hairs.

Men and women can suffer from depression, insecurity and other negative emotions that can be brought on by hair loss. In the case of women, specifically, 40% of women with alopecia have had marital problems as a consequence, and about 63% claim to have had career related problems. It may sound trivial but to millions it is no minor matter: psychiatric disorders are more common in people with alopecia than in the general population, suggesting that those with alopecia may be at higher risk for developing a serious depressive episode, anxiety disorder, social phobia, or paranoid disorder.

Issues with baldness are evident the world over: 40% of men have noticeable hair loss by age 35, 65% by age 60, and 80% by age 80. Up to 50% of women can be affected as well. It's an important problem, especially for the many men and women who dread looking in the mirror in the morning. In addition to these statistics, it is also important to highlight the fact that these numbers have been increasing even more for the past twenty years. The causes for this are not yet clear but it is believed that a combination of factors like changes in diet, environmental pollution and a less healthy lifestyle altogether are serious contributors. Young men and women under the age of 35 are some of the most affected by this increase in incidence.

There remains a need for methods of treating hair loss and promoting hair growth that is useful across a broad spectrum of disorders.

Brief Summary of the Invention

In summary, the invention involves a program for the treatment of hair loss and the regrowth of the patient's own hair. The program is based on an injectable formula, and can also include treatment with a hair lotion and a shampoo. The injectable formula can be applied in a doctor's office, which can also supply the lotion and shampoo.

Prior approaches used as microinjection therapy to treat hair loss suffer from numerous setbacks. Many formulations focus primarily on anti-androgenic effects alone, for example by inhibiting the conversion of testosterone to conversion of testosterone to dihydrotestosterone (DHT). (See, for example, http://www.cocoona.ae/mesotherapyl.asp) To accomplish this, formulations for injection have incorporated synthetic inhibitors such as Finasteride (Propecia) and Dutasteride (Avodart). (See

http://www.allureeyecosmetic.com/mesotherapy.asp) However, these types of compounds can cause a wide range of serious side effects and may not be approved for injection.

Furthermore, compositions incorporating such compounds focus on only this singular cause of hair loss and thus have limited applicability across a wide range of symptomologies and conditions. The present invention treats multiple mechanisms that cause hair loss and thus provides the advantage of treating a broader population.

Other formulations utilize compounds such as Minoxidil (Rogaine). (See, for example, http://midwesthairlosscenter.com/HairLossSolutions.htm) As with the anti-androgen medications, Minoxidil can cause a large number of highly undesirable side effects and has not been approved in the US for injection, but is limited to topical applications. Some injectable therapies utilize a combination of anti-androgen medications and Minoxidil (See

http://hairlossstlouis.com/new-hair-loss-treatment.html), which compounds the drawbacks of each individually. The present invention utilizes a much safer, balanced and logical combination of ingredients and, to the extent synthetic or semi-synthetic compounds are utilized, those components have been shown to be safe for injection.

With other injectable treatments, recommended use is limited by requiring use in conjunction with hair transplantation. (See http://www.nadermedical.com/mesotherapy.html) The present invention does not require hair transplantation.

Finally, there are a great number of injectable therapies that utilize only a limited number of vitamins (see, e.g. http://mincmedspa.com/hair-loss.php) that do not present a robust, complete and demonstrably successful solution.

In general, prior art injectable formulations fail to achieve success across a broad spectrum of symptomologies and therefore have similar results as those described above. These drawbacks can arise from, for example, not treating a broad range of causes of hair loss by focusing on only a limited number of hair loss mechanisms which may start the changes that result in the lack of hair growth such as focusing on increasing circulation without considering fibrosis or microinflammation; focusing only on anti-adrogenic mechanisms or including vitamins but omitting minerals and oligo-elements that can help stop hair loss and promote hair growth.

The invention is an injectable composition for treating hair loss that includes biotin, minerals and oligo-elements, organic silicon, pentoxyfilline, and procaine hydrochloride, in which the minerals and oligo-elements include Boron (B), Sulfur (S). The compositions can include a buffering agent or D-panthenol. In some embodiments, the minerals and oligo- elements also include Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), and Zinc (Zn). In embodiments, the minerals and oligo- elements include Nickel (Ni), Vanadium (Va) and combinations thereof. These and other embodiments can also include one or more of the minerals and oligo-elements Calcium (Ca), Magnesium (Mg), Potassium (K), Chlorine (CI), Lithium (Li), Iodine (I), and Copper (Cu).

Embodiments of the composition can further include triamcinolone. Compositions of the invention can further include zinc sulphate. Some embodiments can include one or more of Serenoa repens; capsaicin; bimatoprost; lanatoprost; essential amino acids; Follicusan; cell growth factors; stem cells; Astressin-B; Fullerenes (for example as a vehicle); Asiasari Radix extract; Ginseng extract; Cyoctol; and RU 58841.

Amounts of the various components of the invention can be, for example, about 0.5 mg/mL biotin, about 0.5 mg/mL organic silicon, about 2 mg/mL pentoxyfilline, about 2 mg/mL procaine, about 5.0 mg/mL D-panthenol. The pH of the composition can be controlled to be between about 5.3 and about 5.7.

Compositions of the invention can be used to treat hair loss due to a disorder such as alopecia areata, androgenic alopecia, frontal fibrosing alopecia, and effluvium.

The invention is also a method of treating hair loss in a subject in need of treatment that includes the steps of preparing a composition according to the invention and injecting the composition into the scalp of the subject at a plurality of locations in the area suffering from hair loss. In embodiments, the injection locations can be separated by from about 1.5 to about 2.0 cm. About 0.2 mL of the composition can be injected at each of the locations. The composition can be prepared from a plurality of stock solutions, where each of the stock solutions contains one or more components of the composition. In some methods of practicing the invention, a second composition that may be the same as or different from the first composition is prepared and injected into the scalp at a plurality of locations, about one month after injecting the first composition. The composition can be injected repeatedly at one or more predetermined time intervals, for example, once a month, once every two months, once every three months or once every six months. In a particular method, the composition is injected once a month for six months, once every two months for the next six months, once every three months for the next year and six months thereafter until treatment ceases. The invention is also a kit for preparing a composition according to the invention, where the kit includes a plurality of containers, each of the containers containing a stock solution that includes one or more components of the composition. In some embodiments, at least one of the containers contains a stock solution comprising more than one component of the formulation. The kit can also include one or more of a comb, a marker for marking injection points, a syringe for injecting the composition, pipettes or other instruments for measuring stock solutions in the preparation of composition, cotton swabs, alcohol, and alcohol wipes.

Further objectives and advantages, as well as the structure and function of preferred embodiments will become apparent from a consideration of the description, drawings, and examples.

Brief Description of the Drawings

FIGS. 1A, IB and 1C depict exemplary injection patterns in patients with differing patterns of hair loss;

FIG. 2A and 2B depict a first patient with Alopecia areata before and after treatment, respectively, according to the invention;

FIG. 3A and 3B depict a second patient with Alopecia areata before and after treatment, respectively, according to the invention;

FIG. 4A and 4B depict a third patient with Alopecia areata before and after treatment, respectively, according to the invention;

FIG. 5A and 5B depict a fourth patient with Male Alopecia before and after treatment, respectively, according to the invention;

FIG. 6A and 6B depict a fifth patient with Male Alopecia before and after treatment, respectively, according to the invention;

FIG. 7A and 7B depict a sixth patient with Male Alopecia before and after treatment, respectively, according to the invention;

FIG. 8A and 8B depict a seventh patient with Female Alopecia before and after treatment, respectively, according to the invention;

FIG. 9A and 9B depict a eighth patient with Female Alopecia before and after treatment, respectively, according to the invention; and FIG. 10A and 10B depict a ninth patient with Female Alopecia before and after treatment, respectively, according to the invention.

Detailed Description of the Invention

Embodiments of the invention are discussed in detail below. In describing

embodiments, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected. While specific exemplary embodiments are discussed, it should be understood that this is done for illustration purposes only. A person skilled in the relevant art will recognize that other components and configurations can be used without parting from the spirit and scope of the invention. All references cited herein are incorporated by reference as if each had been individually incorporated.

As used herein, the terms "prevent," "preventing," "prevention," "prophylactic treatment" and the like refer to reducing the probability of developing a disorder or condition in a subject, who does not have, but is at risk of or susceptible to developing a disorder or condition.

By "subject" or "patient" is meant a mammal, including, but not limited to, a human or non-human mammal, such as a bovine, equine, canine, ovine, or feline.

As used herein, the terms "treat," treating," "treatment," "therapeutic" and the like refer to reducing or ameliorating a disorder and/or symptoms associated therewith. It will be appreciated that, although not precluded, treating a disorder or condition does not require that the disorder, condition or symptoms associated therewith be completely eliminated.

As used herein, "about" means within ten percent (10%) above or below the recited number, unless the context implies otherwise.

The terms "formulation" and "composition" are used interchangeably herein.

The present invention is directed toward a formulation and method to prevent hair loss and promote hair growth. Some information is known about the causes of hair loss and why baldness begins. For example, it is known that increased production of DHT can cause hair loss. However, simply blocking production of DHT does not necessarily cause hair to regrow, although it can retard the progression of baldness. Further, it has been observed that certain treatments, such as Minoxidil, are more successful if utilized shortly after the onset of hair loss, for example within about five years, but that over time, treatment becomes less likely to be successful. However, success rates with either Minoxidil or Finasteride rarely go above 40% and these treatments have to be taken for life, otherwise baldness reinstates itself very quickly after stopping its use.

Without being bound by theory, it is believed that one reason the present invention is so successful in not only retarding hair loss but in actually promoting hair growth is that it treats not only the factors that initiate baldness, but also stimulates follicles to regenerate hair growth. The invention helps to rehabilitate the hair follicle and take it out from a "dormant" phase to a "wake" phase by regenerating the conditions around the follicle that will allow it to reactivate its working function and to recuperate its capacity to produce healthy hair again. If has been thought that, after hair loss has progressed for some time, hair follicles die. This is one reason that prior art systems are sometimes recommended to be used only in conjunction with hair transplants. This was also believed to be a reason that particular therapies, for example Minoxidil treatment, are successful only if begun shortly after the onset of hair loss, i.e. before follicle death. In developing the present invention, it was hypothesized that hair follicles do not in fact die, but rather go into a state of dormancy. Accordingly, the present formulation was developed using factors that re-invigorate the hair follicle growth, bringing them out of a dormant state and causing hair growth to resume.

Baldness is a problem with multiple causes and surrounding circumstances, requires a method with multiple solutions. Formulations of the present invention include a number of components with a broad spectrum of beneficial effects and as a result can treat a number of causes of hair loss and lack of hair growth which in turn makes it more successful in addressing a large number of the currently known causes for baldness. Prior approaches tend to use a very small number of ingredients because it has been the general belief that injecting more than three substances in the dermis (the middle layer of the skin) was not possible or would not result in the presence of sufficient amounts of individual components to be effective. However, as demonstrated by the present invention, treatment with a broad spectrum of components has proven that it is not only possible to utilize multiple components, but very beneficial for the patient. At one time it was commonly believed that the only problem causing hair loss was related to the testosterone. However, it is now known that there are multiple causes that can operate individually or collectively to cause hair loss and lack of hair growth. The present formulation and method addresses many of these factors.

The present formulations include minerals and oligo-elements (or trace elements) that had not been used before in injectable hair growth compositions. These include macro and micro minerals in very small concentrations to act where needed and in an amount the hair follicle needs. Macro minerals refers to minerals that the body uses in greater amounts than the micro minerals. Although both are present in only small amounts, they fulfill a variety of functions. These minerals are found in the body in proportion equal to or less than 0.01 % of total body weight. However, their presence is important for the proper functioning of many biological processes of living beings; for example, effects are closely linked with the correct performance of enzymes. They also participate in various metabolic processes and are very important in the structure of many proteins and other substances in the body, by stimulating or inhibiting hormone functions, regulating physiological responses, etc. They are biocatalysts involved in the biochemical transformation of large quantities of substrates, from which different components required for vital processes are produced. It is known that the imbalance of some of these minerals in the body has a significant role in the pathogenesis of some types of alopecia. The relationship between vitamins, minerals and the health of the hair has been well established through the observation of the alteration of the hair in different diseases concomitant with nutritional deficiencies or the lack of some of the vitamins and minerals.

Although treatments exist that involve injecting some of the components of the present formula into the scalp, the pH of the formulation has not been previously considered. An incorrect pH can result in too painful a treatment, which could decrease patient compliance and decrease the likelihood of successful treatment even if the formulation were adequate to treat the particular patient's problems. The present formulation take this into consideration as well. As a result the pH is controlled and balanced to minimize pain as much as possible, rendering it almost imperceptible. No previous injectable approach to treating hair loss, and in fact very few topical or other treatments have achieved the high rate of success experienced by the present invention. As a result of the above features and considerations, success rates of over 80% in men and over 92% in women have been observed when utilizing the present invention.

Formulations

Formulation according to the present invention, as exemplified by the non-limiting examples appended hereto, can include a number of ingredients including biotin, minerals and oligo-elements (or trace elements), organic silicon, pentoxyfilline, procaine hydrochloride, and bicarbonate (in saline solution). The formulation can also include D-panthenol. Minerals and oligo-elements can include Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), and Zinc (Zn). Additional minerals can include Calcium (Ca), Magnesium (Mg), Potassium (K), Chlorine (CI), Lithium (Li), Iodine (I), Boron (B), Sulfur (S), and Copper (Cu). The formulation can also include Nickel (Ni) and Vanadium (Va), and/or Zinc Sulphate. In exemplary embodiments, the minerals and oligo-elements are used in

homeopathically acceptable concentrations. Alternatively, minerals and oligo-elements can be used in traditional pharmaceutical or nutritional concentrations.

As previously stated, the various components of the present formulation treat a variety of aspects of hair loss. Additionally, the components can act to re-invigorate hair follicle activity, promoting a return from dormancy and follicle health. Without being bound by theory, the various components could provide the following advantages:

Biotin participates in and/or regulates cellular growth, fatty acids production, fats and amino acids metabolism, sugar levels maintenance. It can also regulate sebaceous secretion. Biotin also assists in incorporating amino acids in the formation of keratin, which aids in hair formation and can promote restoration of hair pigmentation or prevent loss of pigment in the hair.

D-panthenol participates in the metabolism and synthesis of proteins, fats and carbohydrates. Like biotin, D-panthenol can help regulate sebaceous secretion, and

incorporates amino acids in the formation of keratin and can promote restoration of hair pigmentation or prevent loss of pigment in the hair. Additionally, D- panthenol hydrates the corneal strata improving hair shaft permeability.

Minerals and oligo-elements can have many beneficial effects and are part of the natural balance in biological systems. They are generally indispensable in every biologic process of living beings. In treating hair loss, deficiencies can often be found in one or more of Chromium, Calcium, Magnesium and Zinc. Among the minerals, zinc is found in the highest concentration after Iron in biological systems. Zinc is an endocrine regulator and participates in cellular integrity, It is also an antioxidant, immune regulator, and anti-inflammatory. Zinc integrates and/or serves as cofactor for over 300 enzymes, and is also an anti-androgen. In addition, copper is essential for the formation of pigmentation and can be very important.

Organic silicon or organic silicea can act as a cellular metabolism and division regulator, and can suppress free radicals, e.g. by acting as an antioxidant or reorganizing cell membranes and make them more resistant to the attack of free radicals, thus providing anti aging effects. Organic silicon can have restructuring and hydrating effects; the binding of silicon molecules to proteins and mucopolysaccharides, surrounded by water molecules linked by hydrogen bonds, simulates a tissue that is able to maintain the hydration of the epidermis. It can also have cell- stimulant action by stimulating the functioning of the cells of the dermis and the hair follicle (e.g., fibroblasts and keratinocytes). Organic silicon can also act as an anti-inflammatory. In vivo studies have shown that silanols inhibit the local infiltration of white blood cells and the onset of clinical signs that characterize the inflammation, such as erythema and edema.

Studies in vitro show, for its part, the silanols also inhibit the release of interleukins, e.g., Interleukin 1 by keratinocytes in culture media when exposed to UV radiation Organic silicon can be indispensable in the synthesis of collagen and elastin. It can act as an anti-sclerosis agent, provide hydrating action, and can act as an anti-inflammatory. Organic silicons include silanol salicylate, monomethylsilanetriol or dimethylsilanediol, are monomethyltrisilanol mannuronate and methylsilanol mannuronate, dimethyl oxobenzodioxasilane, and dimethylsilanol hyaluronate.

Pentoxyfilline can act as a vasodilator, endothelium protector, and immune modulator. It is a hyper-coagulation regulator and has anti-inflammatory properties. In addition to its anesthetic and pain relief properties procaine hydrochloride, is a vasodilator and anti-histaminic. It improves hair color, and promotes restoration of original hair color. It is also a cell membrane stabilizer and can act to repolarize cells.

Bicarbonate, for example sodium bicarbonate, is utilized in the formulation as a vehicle to dilute the other ingredients. It also serves as a buffer. Bicarbonate can act as a buffering agent to balance pH, resulting in a decrease pain at the time of injection and increasing active ingredients absorption. Other biologically acceptable buffering agents can also be used.

In exemplary embodiments, certain ingredients traditionally used to treat hair loss are intentionally omitted. Examples of components that can be omitted include therapeutic agents that are not approved for injection, for example Minoxidil and certain anti-androgenic compounds, even though there may be some benefits to such compounds. Certain minerals and oligo-elements can also be intentionally omitted. Examples of minerals and oligo-elements that can be omitted include gold, fluoride, neon and aluminum.

In an embodiment of the present application, referred to herein as the first basic formulation according to the present invention, the composition includes biotin, minerals and oligo-elements (or trace elements), organic silicon, pentoxyfilline, and procaine hydrochloride. The minerals and oligo-elements include Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), Boron (B), Sulfur (S), and Zinc (Zn). A buffer, for example sodium bicarbonate, may also be present. The composition may be provided in, for example, a saline solution.

In an embodiment of the present application, referred to herein as the second basic formulation, the composition includes biotin, D-panthenol, minerals and oligo-elements (or trace elements), organic silicon, pentoxyfilline, and procaine hydrochloride. The minerals and oligo-elements include Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), Boron (B), Sulfur (S), and Zinc (Zn). A buffer, for example sodium bicarbonate, may also be present. The composition may be provided in, for example, a saline solution.

In another embodiment of the present application, referred to herein as the third basic formulation, the composition includes biotin, minerals and oligo-elements (or trace elements), organic silicon, pentoxyfilline, and procaine hydrochloride. The minerals and oligo-elements include Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), Zinc (Zn), Calcium (Ca), Magnesium (Mg), Potassium (K), Chlorine (CI), Lithium (Li), Iodine (I), Boron (B), Sulfur (S), Copper (Cu), Nickel (Ni) and Vanadium (Va). A buffer, for example sodium bicarbonate, may also be present. The composition may be provided in, for example, a saline solution.

In another embodiment of the present application, referred to herein as the fourth basic formulation, the composition includes biotin, D-panthenol, minerals and oligo-elements (or trace elements), organic silicon, pentoxyfilline, and procaine hydrochloride. The minerals and oligo-elements include Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), Zinc (Zn), Calcium (Ca), Magnesium (Mg), Potassium (K), Chlorine (CI), Lithium (Li), Iodine (I), Boron (B), Sulfur (S), and Copper (Cu). A buffer, for example sodium bicarbonate, may also be present. The composition may be provided in, for example, a saline solution.

In another embodiment of the present application, referred to herein as the fifth basic formulation, the composition includes biotin, minerals and oligo-elements (or trace elements), organic silicon, pentoxyfilline, and procaine hydrochloride. The minerals and oligo-elements include Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), and Zinc (Zn). Additional minerals can include Calcium (Ca), Magnesium (Mg), Potassium (K), Chlorine (CI), Lithium (Li), Iodine (I), Boron (B), Sulfur (S), and Copper (Cu). A buffer, for example sodium bicarbonate, may also be present. The composition may be provided in, for example, a saline solution.

Another embodiment of the present application, referred to herein as the sixth basic formulation, includes all of the materials of the first basic formulation and adds zinc sulphate. Still other embodiments includes all of the materials of the one of the second through fifth basic formulations and adds zinc sulphate.

A number of additional optional ingredients can also be utilized with any of the above mentioned formulations. Additional components may be useful in cases that provide difficult to treat or where alopecia is wide spread or has gone untreated for extended periods. For example, in the treatment of alopecia areata or frontal fibrosing alopecia, triamcinolone can be added. Other ingredients that can be added could include Serenoa repens; capsaicin; bimatoprost; lanatoprost; essential amino acids; follicusan; cell growth factors; stem cells; astressin-b; fullerenes (for example as a vehicle); Asiasari Radix extract; ginseng extract;

cyoctol; and RU 58841. Preparation of the Formulations

In general, formulations used in the present invention are prepared from stock solutions of the various components which are combined to provide the component as part of a final formulation in a desired amount. Stock solutions can be individually prepared and combined immediately prior to injection, for example in a doctor's office. Alternatively, the formulations can be prepared in advance and provided to the treating physician in a finished or ready to use state. Intermediate types of preparations are also envisioned and within the scope of the present invention. For example, an intermediate preparation can include a number of components, but less than all of those used in the final formulation, which be combined into individual packages or vials that are combined immediately before use. Thus, rather than each component being provided individually and mixed immediately prior to use, certain components are present in a number of premixed packages, each containing one or more of the components of the formulation, and the premixed packages are then combined immediately prior to use. This type of preparation can be advantageous where various components lack long term stability when combined.

Accordingly, in one aspect, the present invention is a kit. The kit can include a plurality of containers, for example vials, each containing a stock solution. The stock solution in each container can include one or more components to be present in the final formulation. For example, a kit could comprise a first container having contained therein a stock solution of biotin, a second container having contained therein a stock solution of D-panthenol, a third container having contained therein a stock solution of minerals and oligo-elements, a fourth container having contained therein a stock solution of organic silicon, a fifth container having contained therein a stock solution of pentoxyfilline, a sixth container having contained therein a stock solution of procaine hydrochloride, and a seventh container having contained therein a solution of bicarbonate or other buffer. The various solution can be prepared in an aqueous solution, for example a saline solution. The various components in the stock solutions can be present in amounts as specified elsewhere in the present specification.

In other embodiments, the kit can exclude containers of components not used in the particular formulation. For example, a kit for the preparation of the first or third basic formulation as described above may not have a container with a stock solution of D- panthenol. Kits can also include containers having contained therein optional ingredients. For example, a kit could contain an eighth container having contained therein a stock solution of triamcinolone.

In still other embodiments, the kit can include various components combined in a single container, rather than in multiple containers, and other components contained in containers individually or with other containers having one or more components in a stock solution. For example, rather than the kit including seven containers as described above, the first and fourth containers could be replaced by a single container having contained therein a stock solution that includes both biotin and organic silicon at suitable concentrations. As will be appreciated, there are numerous combinations and permutations of how the various components could be combined, such that the total number of vials in the kit could be as few as two and as many as there are ingredients in the formulation to be prepared. The kit can also include containers with stock solutions of optional ingredients to allow preparation of more than one specific formulation from a single kit.

In some embodiments, any of the kits described herein could contain other components, as well as tools or implements useful in practicing the invention. For example, the kit could include one or more of a comb, a marker for marking injection points, a syringe for injecting the formulation, pipettes or other instruments for measuring stock solutions in the preparation of formulations, cotton swabs, alcohol, alcohol wipes, and the like.

Exemplary methods and concentrations for preparing the injectable formulation of the invention are described below. However, in view of the various methods for preparing the formulation, persons skilled in the art will be able to routinely vary the quantity of various ingredients in the stock solutions or pre-prepared vials in order to arrive at suitable final concentrations of components suitable for use in the present invention. An example of preparing the second basic formulation described above utilizes a stock solution of biotin containing from about 2.5 mg/mL to about 7.5 mg/mL, for example about 5.0 mg/mL biotin; a stock solution of D-panthenol containing from about 25 mg/mL to about 75 mg/mL, for example about 50 mg/mL D-panthenol; a stock solution of organic silicon containing from about 2.5 mg/mL to about 10 mg/m L, for example about 5.0 mg/mL organic silicon; a stock solution of pentoxyfilline containing from about 10 mg/mL to about 75 mg/mL, for example about 20 mg/mL pentoxyfilline; and a stock solution of procaine hydrochloride containing from about 5 mg/mL to about 20 mg/mL, for example about 10 mg/mL procaine hydrochloride, or a 1% solution of procaine hydrochloride. In addition, a stock solution of minerals and oligo-elements can be prepared.

The stock solution can include minerals and oligo-elements. These are commonly prepared using standard homeopathic methods and can be present in about the following amounts as expressed by their homeopathic potencies where the letter and number after each element refers to its homeopathic dilution using standard notation. For example, D8 indicates a 10:1 dilution repeated 8 times and CIO means a 100:1 dilution repeated 10 times. The stock solution can contain one or more of the following: Calcium (D8), Magnesium (D6), Potassium (D6), Chlorine (D8), Molybdenum (CIO), Iron (D10), Chromium (D30), Cobalt (D30), Lithium (D10), Selenium (CIO), Manganese (D10), Nickel (C30), Vanadium (D30), Iodine (D10), Zinc (D30), Boron (C6), Sulfur (CIO), and Copper (C-O). These minerals and oligo-elements can be utilized in typical homeopathic forms.

A bicarbonate solution can be prepared by adding about 1.0 to about 5.0 mL, for example about 2.0 mL, of 7.5% (44.6 mEq/50 mL) sodium bicarbonate (Na HC03) to about 25 to 100 mL, for example about 50 mL, of water or a normal saline solution, for example a 0.09% saline solution.

The stock solutions described above are further diluted to prepare the final formulation. An exemplary final formulation can be prepared by combining, for example, about 0.5 mL of the biotin stock solution, about 0.5 mL of the D-panthenol stock solution, about 0.5 mL to about 5.0 mL, for example about 1.0 mL or the stock solution of minerals and oligo-elements, about 0.5 mL of the stock organic silicon solution, about 0.5 mL of the stock pentoxyfilline solution, about 1.0 mL of the stock procaine solution and about 1 mL of the stock bicarbonate solution. According to these exemplary dilution ranges, the final concentrations of components in the formulation are about 0.5 mg/mL biotin, about 5.0 mg/mL D-panthenol, about 0.5 mg/mL organic silicon, about 2 mg/mL pentoxyfilline, and about 2 mg/mL procaine.

The amounts described can be varied to provide a sufficient amount of the formulation for a particular treatment. For example, if the area to be treated is about 6 cm X 6 cm in size and the 0.2 mL of the formulation is to be injected at 2.0 cm intervals, about 16 injections, or about 3.2 mL of formulation is required and preparing 5 mL of the formulation (as outlined above) is sufficient. However, if the application area or injection amount is larger, or if the injection interval is smaller, it may be necessary to scale up the amounts outlined above to provide a sufficient amount of the formulation.

In preparing the formulation, the pH of the final formulation is checked. The pH should be between about 5.0 and 6.0, for example between about 5.3 and 5.7 of about 5.5. If the pH varies below of this range, additional bicarbonate solution is added to maintain the pH.

Although rarely encountered, if the pH is too high, it can be lowered by the addition of an acid, for example a 20% hydrochloric acid solution.

In preparing other basic formulations as outlined above, similar amounts of individual components can be used, and the final volume adjusted, through addition of more or less water or bicarbonate stock solution, for example, to obtain the desired final concentration of each component. If triamcinolone is used in the formulation, it can be added as a stock solution to provide a final triamcinolone concentration of about 2.0 mg/mL to about 15 mg/mL, for example about 10 mg/mL. If zinc sulfate is used in the formulation, a stock solution can have a concentration of about 2.0 mg/mL. The stock solution can be added to the formulation to provide a final zinc sulphate dosage of about 100 to about 500 g per injection.

Method of Treatment

According to the present invention, the formulation can be used as an injectable to prevent, halt the progression of, or reverse hair loss, and promote hair growth. The

formulation is useful in treating a broad spectrum of alopecia that results from a broad range of causes or disorders, for example, androgenic alopecia, alopecia areata, frontal fibrosing alopecia and effluviums, for example telogen and anagen effluvium. The present invention is particularly useful in the treatment of alopecia areata, with success rates close to 100%. For the treatment of androgenic alopecia in men (male pattern baldness) success rates of approximately 85% can be achieved with the present invention. In general, a treatment is considered successful if it results in a satisfactory response in terms of the recovery of the lost hair in the view of the patient. Quantitatively, a treatment is successful if it results in hair growth within six to twelve months and retains new hair for at least five years, with periodic controls of at least once a year.

Hair loss in females can have varying causes including androgenic alopecia (termed female pattern baldness) and effluviums, all of which result in a wide spread hair loss or thinning and can cause severe emotional distress. Utilizing the present invention, results obtained in women are even better than those obtained in men, reaching at least 92% success rates.

The process for using the present formulation is envisioned in a way that is intended to be relatively simple and straightforward. Typically, the procedure can be conducted in a doctor's office in the time it takes for any typical in-office procedure. General anesthesia is not required and no specialized instruments or care is needed, although the patient can generally be monitored for adverse reactions to components, pain, swelling, infection and the like.

Generally, the patient's clinical history is delineated, especially to inquiring about risk factors associated with hair loss and possible sensitivity to various components. This takes from 20 to 30 minutes. If justified by the clinical data collected from the patient, the first round of injections can be administered during a first office visit.

In treating the patient, the patient's existing hair is combed in straight lines. The patient's scalp is carefully cleaned with alcohol, for example as an alcohol wipe or an alcohol soaked cotton ball as a disinfectant. The treating physician determines the pattern in which the injections are to be applied. Generally, injections are applied throughout the alopecic zone, i.e. the area with the missing or thinning hair, about 1.5 to 2.0 cm apart. Exemplary injection patterns are shown in Figure 1A-C. Prior to injection, the pH of the formulation is checked and, if necessary, adjusted by the addition of bicarbonate solution. Approximately 0.2 ml of the formulation is applied at each injection site in a pattern that completely encompasses the alopecic zone. For example, injections can start at the crown or at the posterior-most border of the alopecic zone, and be applied from left to right. Once the opposite border (from the start point) is reached, a new line is started until the entire alopecic zone is injected. Injections are continued until the process is complete.

A second treatment is generally administered about 30 days after the first. Injections are applied in the same way as for the first set of injections. The timing of use of the present invention is different from that typically used for prior injection treatments, which is often much more frequent. More specifically, injection treatments using prior formulations are generally administered on approximately a weekly basis. The less frequent application according to the present invention affords several advantages. Because treatment is less frequent, costs are lowered. Also, the patient is subjected to less trauma, which can improve patient compliance providing even more improved results.

After the second treatment, a regular treatment plan is developed. An exemplary treatment plan can include:

• One session of injections every month until at least four additional sessions (six total) are completed;

• After the first six sessions, one session every two months until at least three

sessions are completed;

• Afterwards, one session every three months for another year; and

• One session every six months for maintenance.

There can be variations of these frequencies and times depending on personal responses to the treatments.

The process of the present invention provides several advantages including that:

• Frequency is monthly at the beginning (instead of weekly as in most of the other treatment programs);

• There are fewer or no side effects;

• Success rates are well over 80% in men and over 92% in women;

• In most cases, new hair grows in the original color of the patient;

• If gray hair was present, it often disappears with the treatment; and

• Pain is minimal. Aspects of the present invention are further evidenced and demonstrated by the limiting examples set forth below, which are illustrative and not intended to limit the invention.

EXAMPLE 1

The following formulation was made by preparing stock solutions of the various components in the indicated amounts. Portions of each stock solution were then combined in the amounts shown to provide a formulation according to the invention.

AMOUNT OF STOCK

CONCENTRATION IN STOCK

INGREDIENT SOLUTION IN SOLUTION FORMULATION

Procaine

Hydrochloride (1%; 10 mg/ml) 1.0 cc

2 cc of 7.5% (44.6 mEq/50 ml)

Sodium Bicarbonate

Bicarbonate in

(NaHC03) are added to a 50

normal saline 1.0 cc

ml bag of normal saline

solution

EXAMPLE 2

AMOUNT OF STOCK

CONCENTRATION IN STOCK

INGREDIENT SOLUTION IN SOLUTION FORMULATION

Procaine

Hydrochloride (1%; 10 mg/ml) 1.0 cc

2 cc of 7.5% (44.6 mEq/50 ml)

Sodium Bicarbonate

Bicarbonate in

(NaHC03) are added to a 50

normal saline 1.0 cc

ml bag of normal saline

solution

EXAMPLE 3

AMOUNT OF STOCK

CONCENTRATION IN STOCK

INGREDIENT SOLUTION IN SOLUTION FORMULATION

2 cc of 7.5% (44.6 mEq/50 ml)

Sodium Bicarbonate

Bicarbonate in

(NaHC03) are added to a 50

normal saline 1.0 cc

ml bag of normal saline

solution

EXAMPLE 4

AMOUNT OF STOCK

CONCENTRATION IN STOCK

INGREDIENT SOLUTION IN SOLUTION FORMULATION

2 cc of 7.5% (44.6 mEq/50 ml)

Sodium Bicarbonate

Bicarbonate in

(NaHC03) are added to a 50

normal saline 1.0 cc

ml bag of normal saline

solution

EXAMPLE 5

Patients with Alopecia Areata, Male Alopecia and Female Alopecia were treated with a composition as described in Example 1 above. The formulation was injected once a month for six months. The results are shown in Figures 2-10, where the Figure labeled A is before treatment and the Figure labeled B is after treatment. The patients shown in Figures 2-4 suffered from Alopecia Areata; the patients shown in Figures 5-7 suffered from Male Alopecia and the patients shown in Figures 8-10 suffered from Female Alopecia.

The embodiments illustrated and discussed in this specification are intended only to teach those skilled in the art the best way known to the inventors to make and use the invention. Nothing in this specification should be considered as limiting the scope of the present invention. All examples presented are representative and non-limiting. The above- described embodiments of the invention may be modified or varied, without departing from the invention, as appreciated by those skilled in the art in light of the above teachings. It is therefore to be understood that, within the scope of the claims and their equivalents, the invention may be practiced otherwise than as specifically described.

Claims

WHAT IS CLAIMED IS:

1. An injectable composition for treating hair loss comprising biotin, minerals and oligo- elements, organic silicon, pentoxyfilline, and procaine hydrochloride;

wherein the minerals and oligo-elements comprise Boron (B), Sulfur (S).

2. An injectable composition for treating hair loss comprising biotin, minerals and oligo- elements, organic silicon, pentoxyfilline, procaine hydrochloride, and a buffering agent.

3. The composition of claim 1 or 2, further comprising D-panthenol.

4. The composition of one of claims 1-3, wherein the minerals and oligo-elements further comprise Chromium (Cr), Cobalt (Co), Iron (Fe), Iodine (I), Manganese (Mn), Molybdenum (Mo), Selenium (Se), and Zinc (Zn).

5. The composition of one of claims 1-4, wherein the minerals and oligo-elements further comprise Nickel (Ni), Vanadium (Va) and combinations thereof.

6. The composition of one of claims 1-5, wherein the minerals and oligo-elements further comprise one or more of Calcium (Ca), Magnesium (Mg), Potassium (K), Chlorine (CI), Lithium

(Li), Iodine (I), and Copper (Cu).

7. The composition of one of claims 1-6, further comprising triamcinolone.

8. The composition of one of claims 1-7, further comprising zinc sulphate.

9. The composition of one of claims 1-8, further comprising one or more of Serenoa repens; capsaicin; bimatoprost; lanatoprost; essential amino acids; Foilicusan; cell growth factors; stem cells; Astressin-B; Fullerenes (for example as a vehicle); Asiasari Radix extract; Ginseng extract; Cyoctol; and RU 58841.

10. The composition according to any one of claims 1-9, comprising about 0.5 mg/mL biotin, about 0.5 mg/mL organic silicon, about 2 mg/mL pentoxyfilline, and about 2 mg/mL procaine.

11. The composition according to any one of claims 3-10, comprising about 5.0 mg/mL D- panthenol.

12. The composition of any one of claims 1-11, wherein the pH of the composition is between about 5.3 and about 5.7.

13. The composition of any one of claims 1-12, wherein the hair loss is due to a disorder selected from alopecia areata, androgenic alopecia, frontal fibrosing alopecia, and effluvium.

14. The composition of claim 13, wherein the disorder is alopecia areata.

15. A method of treating hair loss in a subject in need of treatment comprising preparing a composition according to any one of claims 1-12; and

injecting the composition into the scalp of the subject at a plurality of locations in the area suffering from hair loss.

16. The method of claim 15, wherein each of the plurality of locations is separated from a nearest location by from about 1.5 to about 2.0 cm.

17. The method of one of claims 15 and 16, further comprising preparing the composition from a plurality of stock solutions, each of the stock solutions containing one or more components of the composition.

18. The method of one of claims 15-17, wherein about 0.2 mL of the composition is injected at each of the plurality of locations.

19. The method of one of claims 15-18, further comprising

preparing a second composition according to any one of claims 1-12; and

injecting the second composition into the scalp at a plurality of locations, of the subject in the area suffering from hair loss;

wherein the second composition may be the same as or different from the first composition; and

wherein injecting the second composition is performed about one month after injecting the composition.

20. A method of treating hair loss in a subject in need of treatment comprising:

(a) preparing a composition according to any one of claims 1-12;

(b) injecting the composition into the scalp at a plurality of locations, of the subject in the area suffering from hair loss; and repeating steps (a) and (b) at one or more predetermined intervals.

21. The method of claim 20, wherein the predetermined intervals are once a month, once every two months, once every three months or once every six months.

22. The method of claim 20, wherein the predetermined intervals are once a month for six months, once every two months for the next six months, once every three months for the next year and six months thereafter until treatment ceases.

23. The method of one of claims 15-22, wherein the subject in need of treatment suffers from a disorder selected from alopecia areata, androgenic alopecia, frontal fibrosing alopecia and effluvium.

24. The method of claim 23, wherein the disorder is alopecia areata.

25. A kit for preparing a composition for treating hair loss according to one of claims 1-12, comprising a plurality of containers, each of the containers containing a stock solution comprising one or more components of the composition.

26. The kit of claim 25, wherein at least one of the containers contains a stock solution comprising more than one component of the formulation.

27. The kit of claim 25 or 26, further comprising one or more of a comb, a marker for marking injection points, a syringe for injecting the composition, pipettes or other instruments for measuring stock solutions in the preparation of composition, cotton swabs, alcohol, and alcohol wipes.