WO2016153103A2 - Procédé pour favoriser la pousse des cheveux et empêcher la chute des cheveux d'un patient, composition associée et procédé de préparation de la composition - Google Patents

Procédé pour favoriser la pousse des cheveux et empêcher la chute des cheveux d'un patient, composition associée et procédé de préparation de la composition Download PDF

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WO2016153103A2
WO2016153103A2 PCT/KR2015/004633 KR2015004633W WO2016153103A2 WO 2016153103 A2 WO2016153103 A2 WO 2016153103A2 KR 2015004633 W KR2015004633 W KR 2015004633W WO 2016153103 A2 WO2016153103 A2 WO 2016153103A2
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Prior art keywords
bfgf
patient
hair loss
hair
prp
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English (en)
Korean (ko)
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WO2016153103A3 (fr
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임재현
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Individual
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Priority claimed from US14/665,740 external-priority patent/US9173921B1/en
Priority to AU2015388056A priority Critical patent/AU2015388056B2/en
Priority to BR112017020132A priority patent/BR112017020132A2/pt
Priority to MX2017012125A priority patent/MX2017012125A/es
Priority to CA2979822A priority patent/CA2979822C/fr
Priority to RU2017132712A priority patent/RU2690845C2/ru
Application filed by Individual filed Critical Individual
Priority to EP15886551.9A priority patent/EP3275459A4/fr
Priority to CN201580078177.6A priority patent/CN107708721A/zh
Priority to JP2016576075A priority patent/JP6823463B2/ja
Publication of WO2016153103A2 publication Critical patent/WO2016153103A2/fr
Publication of WO2016153103A3 publication Critical patent/WO2016153103A3/fr
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    • 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
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention comprises at least one of basic fibroblast growth factor (bFGF), platelet rich plasma (PRP) and plasma which can be injected intradermal or subcutaneously to promote hair growth and prevent hair loss.
  • bFGF basic fibroblast growth factor
  • PRP platelet rich plasma
  • the present invention relates to a composition, a method for preparing the same, and a method for promoting hair growth and preventing hair loss in a patient.
  • Hair loss can be a factor that makes you look older than your actual age or makes you look less attractive to others.
  • the causes of hair loss are many and varied, including representatives of natural aging, damage to the hair growth cycle, genetic causes, adverse effects of medications, environmental factors such as allergies, infections, stress, dietary intake and lack of sleep, and / Or other strains of the disease.
  • FIG. 1 is a conceptual diagram showing how baldness (male hair loss) progresses in a large number of male populations.
  • women's hair loss is not accepted as a common and common phenomenon due to social norms, which can stress women suffering from hair loss.
  • thinning hair due to the typical symptoms of female hair loss can cause problems not only to shrink the woman herself but also negatively judge the external image of the female hair loss from others.
  • hair loss such as medicine, surgical operations, and injection procedures.
  • drugs such as minoxidil (Rogains), finasteride (Propecia), and dutasteride (Avodart) are known to have hair loss. Approved as a treatment for.
  • these drugs are effective only when the patient takes the medicine every day, and a long time passes from the start of taking the medicine, and if the drug is discontinued for any reason, there is a possibility that the therapeutic effect between them disappears.
  • some of the therapeutic drugs were not available to women for safety reasons.
  • Surgical methods for treating hair loss include hair follicle transplantation, scalp reduction, head skin transplantation, and injection therapy. Such surgery risks necrosis of the skin at the site of surgery or formation of keloid wound tissue.
  • the number of hair follicles that appear unnatural after surgery or the number of hair follicles that can be safely implanted is not unsatisfactory. (Up to 4000 hair follicles can be implanted per operation, the maximum number of surgeries that can be performed throughout a patient's lifetime is three.)
  • these operations require three to four hours of surgery and post-treatment time. It is necessary, and even in the absence of other complications, it is very inconvenient for the patient because the daily life is impossible for about two weeks after the operation.
  • Platelets are biochemical reservoirs of regulatory molecules, signaling systems, and growth factors that participate in tissue repair and treatment as well as first aid to wounds.
  • the platelet-related growth factors include platelet-derived growth factor (PDGF), transforming growth-factor-beta (TGF-b), and vascular epidermal growth factor (VEGF).
  • PDGF platelet-derived growth factor
  • TGF-b transforming growth-factor-beta
  • VEGF vascular epidermal growth factor
  • EGF epidermal growth factor
  • FGF-2 fibroblast growth factor-2
  • IGF insulin-like growth factor
  • hair loss including (a) Dihydrotestosterone Theory, (b) Gravity Theory, and (c) Blood Supply Theory We reviewed existing theories about this.
  • Dihydrotestosterone Theory is a major theory that assumes that dihydrotestosterone (DHT) binds to certain parts of hair follicles, causing hair follicles to shrink, thus shortening the growth of healthy hair.
  • DHT dihydrotestosterone
  • the theory does not explain to some people why high levels of DHT do not affect hair loss. That is, most men with high levels of DHT are still growing laryngeal and temporal hair, and have healthy hair on areas such as armpits, legs, chest, and genitals.
  • the hair growth cycle consists of three stages: growth phase, degenerative phase, and resting phase.
  • the growth phase hair grows according to the normal hair growth cycle after 4 to 6 years, and after 2 to 3 weeks, the hair growth stops. Take a break of about three months, ready to stop the activity and get out of it.
  • gravity theory thinning of the skin tissue at the hair loss site substantially shortens the growth phase and increases the resting period.
  • the theory is supported by a product called minoxidil, which has been sold as a drug to treat hypertension for the purpose of vasodilation.
  • Hair growth at the hair loss site is one of the additional effects of minoxidil, which has been used to treat hair loss by assisting the blood circulation of the scalp with the vasodilating effect of minoxidil. While patients take minoxidil, the blood supply to the hair follicles increases, causing hair growth to be temporarily active.
  • the present invention has been made in order to overcome the problems of the above-described technology, the main object of the present invention to provide a method and treatment method using a composition that promotes hair growth more efficiently than the conventionally reported method and technology by bFGF do.
  • Another object of the present invention is to provide an additional mixed composition based on bFGF.
  • a method for promoting hair growth and preventing hair loss in a patient according to the present invention is to administer a composition containing an effective amount of an active ingredient comprising bFGF subcutaneously or subcutaneously to the affected part of the patient suffering from hair loss It is characterized by.
  • composition for promoting hair growth and preventing hair loss of the patient is characterized by consisting of bFGF and PRP (platelet rich plasma) mixture, bFGF and plasma mixture, and bFGF and PRP and plasma mixture.
  • bFGF and PRP platelet rich plasma
  • the patient has androgen alopecia, alopecia areata, systemic alopecia, degenerative alopecia, hair loss, telogen hair loss, growing hair loss, scarring alopecia, scar hair loss, scalp thinning, hair loss, infectious hair disease, genetic diseases and chemical treatment It is characterized by having any of the alopecia of hair loss caused by therapy, hormonal imbalance, fungal infection, drug intake.
  • FIG. 1 is a conceptual diagram showing how baldness (male hair loss) progresses in a large number of male populations.
  • 2A is a conceptual diagram illustrating Hamilton-Norwood classification for male hair loss.
  • 2B is a conceptual diagram illustrating Luudwing classification for gynecomastia.
  • FIG. 3A is an exemplary diagram illustrating the first pre-treatment affected condition in Case 1.
  • FIG. 3B is an illustration showing the state of the lesion 4 months after the first treatment in Case 1.
  • FIG. 4A is an exemplary diagram illustrating the condition of the first pretreatment lesion in Case 2.
  • FIG. 4B is an illustration showing the condition of the lesion 56 days after the first treatment in Case 2.
  • 5A and 5B illustrate exemplary head and right head conditions prior to treatment in Case 3;
  • 5A and 5B show exemplary lesions 56 days after the first treatment in Case 3;
  • FIG. 6A is an exemplary diagram illustrating the state of lesion prior to the first treatment in Case 4.
  • FIG. 6A is an exemplary diagram illustrating the state of lesion prior to the first treatment in Case 4.
  • FIG. 6B is an illustration of the lesions after 56 days after the first treatment in Case 4.
  • FIG. 7A is an illustrative diagram showing the condition of the first pretreatment affected in Case 5.
  • 7B is an illustration showing the condition of the lesion 56 days after the first treatment.
  • 8A is a graph depicting hair density change in Cases 1-5.
  • 8B is a graph depicting the average of hair density change in Cases 1-5.
  • the best mode for practicing the present invention is to provide a method for intradermal or subcutaneous administration of a composition containing an effective amount of an active ingredient comprising bFGF to the affected part of a patient suffering from hair loss.
  • Basic fibroblast growth factor is a biopharmaceutical widely used in the market for the healing of various skin diseases and wounds, such as Daewoong Pharmaceutical's FIFERMIN TM.
  • BFGF BFGF according to the present invention, if it has an effect in the prevention and treatment of hair loss, natural or genetically modified type, or their precursor protein; Proteins in which one or more natural or genetically modified types of amino acids are substituted, deleted, or inserted; CDNA-encoded proteins capable of hybridizing native human bFGF under certain conditions (65 ° C., 1 ⁇ SSC, 0.1% SDS or 0.1 ⁇ SSC, 0.1% SDS); At least any one of at least 75% and at least 95% homology with native human bFGF cDNA.
  • each protein gene (cDNA or cDNA plasmid) may be encoded nucleic acid, which may be administered in the form of a liposome-plasmid complex in combination with a single plasmid or expression vector.
  • Plasma is the liquid component that occupies the uppermost part when the blood is centrifuged and is taken from patients who wish to prevent and treat hair loss. (Red blood cells, white blood cells and platelets are in protein salt solution).
  • the plasma consisting of 92% water and 7-8% plasma proteins, accounts for 55% of the total blood volume.
  • the plasma contains globulins containing albumin, a major protein component, and fibrinogen and antibodies involved in blood coagulation.
  • Plasma has a variety of functions, which not only supply important proteins related to blood coagulation and immunity by maintaining adequate blood pressure and volume, but also act as a medium for the exchange of key minerals such as sodium and potassium, Help maintain proper pH.
  • Such plasma is obtained by separating the liquid portion from tangible components such as blood cells in the blood.
  • Platelet-rich plasma is the middle part of the blood when centrifuged from the blood collected from a patient who wants to prevent and treat hair loss, and refers to a plasma with concentrated autoplatelets. It is widely known as a treatment.
  • the PRP contains several growth factors and other cytokines that promote the treatment of bone and tissue.
  • Gel-type plasma is the result of submersion of the plasma in a polypropylene vessel sterilized at the optimum temperature for an optimal time to make the gel form with better retention when the solution is injected into the affected area.
  • the gel-type plasma is formed in the third step.
  • bFGF solution is a commercially available freeze-dried bFGF dissolved in saline, benzalkonium chloride and similar solvents.
  • the bFGF solution is prepared through the fourth step.
  • PRP and bFGF solution is a mixture of PRP and bFGF solution, it is prepared through the fifth step (a).
  • Anesthesia is a method of administering injections or inhalations, which means local anesthesia, neuroblocking, general anesthesia, etc. It blocks the feeling of pain and creates a deep unconscious state where all the senses are removed. Allow the procedure to be performed.
  • “Clinical trial” means the treatment that we have performed in a hospital, as confidential, as described in the following examples, thereby confirming the hair growth effect of the composition.
  • Dermat means administration (preferably injection) of the composition to the dermal tissue of the skin and "subcutaneous” to the adipose tissue of the skin.
  • hair in the present invention is not limited to the hairs on the scalp, and includes all the hairs on the scalp, head, face, and body, including eyelashes, eyebrows, beards, ears, nose, chest, and pubic hair. .
  • “Hair growth” is what induces the growth of new hair cycles, prolongs the growth phase, increases the growth rate of hair and thickens hair.
  • Hair loss and hair thinning mean normal hair density reduction, short hair growth stage, reduced hair thickness, and reduced hair number, which can be caused by aging, genetic causes, or other causes. This can be all.
  • the period of "promoting hair growth” or “treatment” may be determined by at least one of the treatment results such as the number of hairs, the length of the hair, the change in the thickness of the hair, and the like displayed on at least a portion of the treatment site.
  • Prevention related to the hair loss and the thinning of the hair means an effect of reducing the hair loss phenomenon and the hair thinning phenomenon in advance.
  • Therapeutic procedure means the continuation of the first to ninth steps in the examples, with blood collection and blood separation, preparation and use of specific solutions, including bFGF, anesthesia and micro-in the example “methods and procedures” described below Acupuncture treatments, intradermal and subcutaneous injections of the affected area are outlined.
  • a “suitable effective amount” means an amount sufficient for the composition to provide a hair growth promoting effect according to a reasonable benefit-hazard ratio.
  • the amount and ratio of active ingredients within the range of appropriate medical judgments may affect the condition of the affected area, the severity of symptoms, the cause of the onset, the duration of treatment, the specific active ingredient contained, the concentration used, the means of injection utilized, the general health of the patient and the various effects of the infusion Factors such as patient tolerance, other drugs administered to the patient, and specific information about the patient and the physician's expertise.
  • the present invention provides a method of using bFGF in the composition for the prevention and treatment of hair loss in the preparation of a composition for the prevention and treatment of hair loss;
  • the use of bFGF in the prevention and treatment of hair loss including administering bFGF subcutaneously or subcutaneously in a mammal, including humans; Mixing with other substances such as PRP and / or plasma to make bFGF mixtures.
  • 1) bFGF basic fibroblast growth factor, hereinafter referred to as 'bFGF'
  • 2) bFGF and PRP platelet rich plasma, hereinafter referred to as 'PRP'
  • a composition of at least one of the mixtures of plasma may be injected in a certain amount intradermal or subcutaneously to obtain a positive effect of promoting hair growth.
  • BFGF optionally mixed with plasma or plasma and PRP
  • MRS micro-needle therapy system
  • the microneedle therapy is a treatment that promotes the recovery of the affected area by injecting a small amount of fine wounds to the skin.
  • the micro-needle repeatedly penetrates the epidermis of the affected area to give a fine wound, thereby regenerating collagen and elastin. It is possible to facilitate.
  • the composition for 1) to 3) includes fibroblasts that not only promote healing and skin regeneration of the affected area, but also heal and regenerate, thereby thickening the skin of the affected area.
  • PRP and bFGF have been reported to provide an active function in angiogenesis in both in vitro and in vivo experiments and are used to heal wounds. Applicant was able to confirm that particularly healthy blood vessels are formed when using a mixture of PRP and bFGF.
  • the microacupuncture treatment causes a small wound in the affected area when the epidermis is repeatedly penetrated by the micro-needle, and thus the injection of a mixture of plasma and PRP allows new blood vessels to supply more blood to the affected area. Helps heal wounds by forming it.
  • composition according to the invention to be used in the procedure for promoting hair growth may be any specific if it comprises 1) bFGF, 2) a mixture of bFGF and plasma, 3) a mixture of bFGF and PRP, 4) a mixture of bFGF and plasma and PRP. It is, of course, not limited to materials, and can be injected intradermal or subcutaneously through various injection means.
  • Such a composition according to the present invention promotes the transition from the resting phase to the growing phase to normalize (at least improve) the hair growth cycle and increase the shortened growth phase, and at the same time to promote hair growth as well as enhance hair health and hair. It provides a thickening characteristic.
  • the effective dosage of plasma, PRP and bFGF is not particularly limited, but for the treatment of hair loss it is generally preferred to administer 1 mg of bFGF at 0.1 ⁇ g per cm 2 of skin surface.
  • 1 ⁇ g to 100 ⁇ g, 0.1 ⁇ g to 50 ⁇ g, or 10 ⁇ g to 100 ⁇ g of bFGF was used per cm 2 of the skin surface.
  • Plasma may be used from 0.05 ml to 40 ml per cm 2 of skin surface.
  • a state in which 0.05 ml to 20 ml, 0.05 ml to 15 ml or 10 ml to 30 ml is used per cm 2 of the skin surface is presented.
  • PRP may be obtained by collecting blood from a patient to be treated, or may use commercially available marketed merchandise.
  • PRP has a very large number of platelets compared to naturally occurring platelets.
  • the PRP used in the embodiment of the present invention contains at least 2 to 12 times more platelets than the general platelets contained in normal blood.
  • PRP can be used from 0.01 ml to 20 ml per cm 2 of skin surface. In an embodiment of the present invention, a state using 0.01 ml to 15 ml, 0.01 ml to 10 ml, or 5 ml to 20 ml per 1 cm 2 of the skin surface is presented.
  • compositions used in the examples of the present invention comprise (a) an effective amount of bFGF for promoting hair growth, (b-1) platelet rich plasma (PRP), (b-2) plasma, (b-3) ) Is a mixture of PRP and plasma.
  • the amount of PRP and plasma in the composition of the present invention is 0.1 to 10 times or 0.2 to 20 times depending on the respective volume, and 1 ml of bFGF solution may contain 50 to 200 ⁇ g, preferably 100 ⁇ g of bFGF.
  • the composition comprises essentially (a) bFGF in an amount effective to promote hair growth, (b-1) platelet rich plasma (PRP), (b-2) plasma, or ( b-3) optionally comprising a mixture of PRP and plasma.
  • the composition optionally comprises (a) bFGF and (b-1) platelet rich plasma (PRP), (b-2) plasma, or (b-3) a mixture of PRP and plasma.
  • compositions may be injected continuously or as a mixture. For example, it may be mixed just before injecting the composition into the scalp of the patient.
  • the infusion frequency is not particularly limited, and a single infusion may have a sufficient effect. In order to maintain a good effect, it is desirable to inject periodically once a month for a period of time, for example for three months.
  • the infusion cycle may be adjusted according to the patient's hair condition and the patient's desired treatment outcome.
  • the bFGF is currently available commercially only by topical treatment or topical spraying.
  • An example is a commercially available Fiblast Spray (TRAFERMIN TM), and other commercially available bFGF products are available for similar results.
  • bFGF can be used as such or in admixture with a suspension or in admixture with a suspension or emulsifier, details of which will be described below.
  • the PRP and the plasma can be obtained from a patient in need of treatment. For example, on the day of treatment, an appropriate amount of whole blood is drawn from the patient and centrifuged to separate plasma and PRP. Centrifugation can be performed according to known techniques. Whole blood and separated blood (PRP, plasma, etc.) thus obtained are safely stored until used for treatment. Whole blood extraction is determined by the patient's health and affected area. The person who can collect whole blood is not limited to the patient who wants to be treated. Whole blood may be taken one or more days prior to treatment and stored in a suitable environment. As will be described in more detail below, plasma may be used in gel type.
  • bFGF is used as the base composition and optionally a composition including a mixture of the PRP and the plasma is injected intradermally or subcutaneously, one or more steps may be omitted or proceed in a different order.
  • Step 1 draw the right amount of blood from the patient
  • Blood volume may vary depending on the overall health of the patient being treated and the progress of hair loss.
  • the collected blood is preferably used for the treatment of the patient on that day, so that more blood than the required amount is collected.
  • centrifuged From the blood extracted in the first step, plasma, platelet rich plasma (PRP), and red blood cells (RBC) are centrifuged by a centrifugal device. Centrifugation separates PRP from PPP (platelet-poor plasma) and PBC using differences in specific gravity.
  • PRP platelet-poor plasma
  • PBC red blood cells
  • FDA US Food and Drug Administration
  • Both methods involve taking a patient's whole blood before going through two stages of centrifugation (TruPRP, Harvest), designed to separate PRP samples from PPP and RBC.
  • the collected whole blood is an anticoagulant (eg Dex). Preserved by throse-citric acid).
  • the average human platelet count is about 200,000 per ⁇ L, and the therapeutic PRP is about four times more concentrated.
  • ACD-A anticoagulant dextrose solution A
  • EDTA ethylenediaminetetraacetic acid
  • coagulation and platelet aggregation are very different and anticoagulants do not prevent platelet aggregation, but platelet aggregation inhibitors to this are not considered.
  • Step 3 Preparation of Gel-Type Plasma by Plastering a Sterilized Polypropylene Container with Plasma at a Specific Temperature and Time
  • Plasma in sterilization vessels is bathed in boiling water at the optimal temperature (0 ° C to 100 ° C) for optimum time (0 to 10 minutes) to produce a jelly form called gel-type plasma.
  • the gel-type plasma obtained in this step is mixed with the bFGF solution formed in the fourth step below.
  • the mixed solution is again mixed with a portion of the mixture of PRP and bFGF (formed in step 5-b).
  • Jelly forms provide better retention when the solution is injected into the affected area.
  • plasma mixtures and bFGF that have not been submerged at optimum temperatures for a certain time may also be used.
  • the amount and ratio of bFGF and plasma may vary depending on hair loss progression, and the solution thickens the scalp.
  • Step 4 Prepare bFGF Solution
  • bFGF a commercially available lyophilized bFGF is dissolved in 5 ml of saline.
  • bFGF is dissolved as soon as the bFGF solution is made and the bFGF solution is prepared for injection and refrigerated below 10 ° C. for use on the day or within two weeks.
  • Centrifuged PRP and bFGF are mixed with each other in an effective amount to produce an injectable solution, which is provided to promote hair growth.
  • the actual amount of each of these ingredients is determined by the patient's overall health and the state of hair loss progression.
  • bFGF, PRP and plasma may be mixed at a volume ratio of about 1: 0.5 to 2.0: 1.5 to 3.0, but in an embodiment of the present invention, a preferred ratio is 1: 1.09: 2.36 (bFGF: PRP: plasma) in a volume ratio.
  • bFGF PRP: plasma
  • the compositions may each be injected as a mixture rather than applied alone.
  • RPR and bFGF mixtures, bFGF and plasma mixtures or bFGF, PRP and plasma mixtures may be injected.
  • each treatment may comprise the same or a different mixture, which may be determined by the physician providing the treatment following the results of the previous treatment.
  • PRP and bFGF mixtures, and plasma and bFGF and PRP mixtures can be injected in the first and second treatments, respectively, as in the above-mentioned embodiments.
  • different compositions eg, gel-type plasma, PRP, bFGF solution mixture and PRP, bFGF solution mixture
  • Step 6 the patient undergoes anesthesia procedures
  • anesthesia methods such as local anesthesia, neuroblocking and general anesthesia may be used.
  • Step 7 perform microacupuncture therapy (MTS) in the affected area
  • Sterilized microneedle therapy promotes skin regeneration at the treatment site.
  • the MTS promotes recovery of the affected area, promotes absorption of the prepared composition and triggers the inflammation healing process by inflicting fine wounds in the skin at an appropriate rate. That is, the micro-needle repeatedly penetrates the epidermis of the affected area, causing minute wounds, thereby promoting the regeneration of collagen and elastin.
  • Step 8 inject the composition to the affected area
  • the affected area is injected in the appropriate order.
  • These two injections are administered in sequence, either in the subcutaneous or subcutaneously of the affected area through various injection means, with an effective effective amount of 0.1 ⁇ g to 50 ⁇ g or 1 ⁇ g to 100 ⁇ g of bFGF per cm 2, more than 1000 ⁇ g per day. Should not be administered.
  • the appropriate effective amount may vary depending on the progress of hair loss and the general health of the patient.
  • the eighth step is a relatively convenient treatment method because it requires only about 20 to 180 minutes as the injection administration time, the patient can immediately return to daily life the next day, and of course, the shower is also possible.
  • the first to eighth steps are preferably repeated at least once a month, preferably at least three months, if possible, for a longer period (eg, about one year).
  • the frequency of injections can be controlled and complex procedures can be implemented.
  • composition according to the present invention includes various hair loss symptoms such as alopecia areata, resting alopecia, growing alopecia, scarring alopecia, baldness, thinning of the scalp, and hair loss, such as nodular fever, growth phase dropping syndrome, hair loss wall and traction alopecia.
  • hair loss symptoms such as alopecia areata, resting alopecia, growing alopecia, scarring alopecia, baldness, thinning of the scalp, and hair loss, such as nodular fever, growth phase dropping syndrome, hair loss wall and traction alopecia.
  • Infectious hair diseases such as ringworm ringworm, seborrheic dermatitis, and scalp folliculitis
  • Genetic diseases such as androgen alopecia
  • Alopecia due to chemotherapy, radiation therapy, hormonal imbalance eg, thyroid-related diseases such as hypothyroidism and hyperthyroidism, pregnancy, childbirth, birth control pills and changes in life cycle
  • It can be used to treat various hair loss symptoms due to anticoagulants, gout drugs, antidepressants, high blood pressure medications, side effects of certain heart medications, and the like, but is not limited to those described.
  • composition is not only for hair loss due to environmental factors (hair dry) and chemicals (dyeing, bleaching agents, etc.) that are performed for hair care, but also physical / impairment due to diabetes, lupus, malnutrition, surgery, disease, and high fever. It can also be used to treat hair loss associated with physical stress.
  • composition according to the invention is preferably administered several times at regular intervals (eg 2-6 weeks or 3-5 weeks) in the affected area.
  • the composition may be repeatedly administered at least once a month (not more than once a week), and the period of repeated administration is preferably at least 3 months, if possible longer (eg about one year). Do.
  • the frequency of injections can be controlled and complex procedures can be implemented.
  • the composition may comprise a pharmaceutically acceptable carrier.
  • the bFGF according to the present invention may be formed into a suitable formulation according to a general method.
  • the bFGF may be in a solid form such as powder or granules, but in order to obtain the best effect for the prevention and treatment of hair loss, it may be preferable to use an injectable liquid agent such as a solution, an emulsion, a suspension and a gel.
  • a method of mixing bFGF in a solvent or mixing the suspending agent or the emulsion with bFGF may be exemplified to prepare the liquid agent.
  • gelatin and bFGF can be mixed.
  • pharmaceutically acceptable carriers such as solvents, suspending agents, emulsifiers, solubilizers, excipients, binders, tonics, buffers, preservatives, stabilizers, soothing agents, antioxidants, colorants And the like can be formulated to suit the needs of the formulation.
  • the solvent is purified water, saline, Ringer's solution, ethanol (ethanol), propylene glycol (propylene glycol), glycerin (glycerin), polyethylene glycol (polyethylene glycol), macrogol (macrogol), and other hydrophilic solvents such as olive oil, peanut oil, Lipophilic solvents such as sesame oil, camellia oil, canola oil, fatty acid monoglycerides, fatty acid diglycerides, fatty acid esters, liquid paraffin and the like.
  • the suspending agent is stearyl triethanol amine, sodium lauryl sulfate, lauryl aminopropionate, lecitin, benzalkonium chloride, benzalkonium chloride (benzethonium chloride), glyceryl monostearate, polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethyl cellulose, methyl cellulose, hydroxy Hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polysolvates, polyoxyethylene hydrogenated castor oil, gum arabic arabic), bentonite and the like.
  • the emulsifiers are gum arabic, gelatin, lecithin, cholesterol, yolk, bentonite, veegum, cetanol, glyceryl mono Stearates (glyceryl monostearate), methyl cellulose (methyl cellulose), carboxymethyl cellulose (sodium carboxymethyl cellulose), stearic acid (stearic acid) and the like.
  • the solubilizing agent is polyethylene glycol, propylene glycol, propylene glycol, D-mannitol, trehalose, benzyl benzoate, ethanol, tris Trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium acetate, and the like.
  • the excipients are lactose, white soft sugar, D-sorbitol, starch, alpha starch, pregelatinized starch, corn starch, D-mannitol (D- mannnitol, dextrin, crystalline cellulose, gum arabic, low substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, methyl cellulose methyl cellulose, serum albumin and the like.
  • the binder is alpha starch, pregelatinized starch, sucrose, gelatin, gum arabic, methyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose sodium carboxymethyl cellulose, crystalline cellulose, white soft sugar, D-mannnitol, trehalose, dextrin, pullulan, hydroxypropyl Cellulose (hydroxypropyl cellulose), hydroxypropyl methyl cellulose (hydroxypropyl methyl cellulose), polyvinyl pyrrolidone, polyvinyl alcohol, and the like.
  • the tonicity agent is sodium chloride, potassium chloride, glucose, glucose, fructose, mannitol, sorbitol, lactose, sugar, saccharose, glycerin (glycerin), urea (urea) and the like
  • the buffer may include sodium citrate, glycerin (glycerin) and the like
  • the preservatives paraoxy benzoic acid esters paraoxy benzoic acid esters
  • chlorobutanol chlorobutanol
  • benzyl alcohol phenethyl alcohol, dehydroacetic acid, sorbic acid.
  • the stabilizer may include polyethylene glycol, dextran sulfate sodium, amino acid, human serum albumin, and the soothing agent may include glucose sugar, glue, and the like. Calcium gluconate, procaine hydrochloride, and the like, and the antioxidant includes sulfite, ascorbic acid, vitamin D, and the like.
  • the colorant tar pigment
  • caramel caramel
  • colcothar titanium dioxide
  • Ellis & Everard's FD & C blue No. 2 and FD & C red No. FD & C pigments such as 40.
  • the composition for promoting hair growth and treating hair loss may include, in addition to the bFGF, a substance having or expected to have an effect on preventing and treating hair loss.
  • a substance having or expected to have an effect on the prevention and treatment of hair loss include fibroblast growth factor 10 (FGF10), acidic fibroblast growth factor (FGF1), and vascular epidermal growth factor.
  • FGF10 fibroblast growth factor 10
  • FGF1 acidic fibroblast growth factor
  • vascular epidermal growth factor vascular epidermal growth factor.
  • morphogenic substances such as vascular endothelial growth factor (VGEF), insulin-like growth factor (ILGF), hepatocyte growth factor (HGF), epidermal growth factor (EGF), etc. one or more from the group consisting of morphogens).
  • the substances may be further administered subcutaneously or subcutaneously to be used with the composition.
  • the method of administering the composition to the affected area or subcutaneously or subcutaneously for the prevention and treatment of hair loss is not limited to a specific method.
  • FIG. 2A shows the Hamilton-Norwood classification for male hair loss and FIG. 2B shows the Luudwing classification for female hair loss.
  • the sterilized polypropylene vessel containing the plasma is immersed in 100 ° C. water for 5 minutes to form 12 ml of gel type plasma.
  • compositions (a) and (b) are prepared.
  • Anesthesia procedure In particular, it blocks both orbital nerves, trochlear nerves (pullary nerve), and large larynx nerves.
  • MTS microneedle therapy
  • a (a) gel-type plasma, a mixed solution of PRP and bFGF, and (b) a mixed solution of PRP and bFGF are sequentially administered to the site treated with MTS.
  • the temporal part with the least effect of hair loss is the reference point, and the hair density is measured with the Digital Scope BEAUTOPIA IS5000 for comparison with the affected part.
  • Step 3- The plasma from step 2 was placed in a sterile container and submerged in 100 ° C. water for 5 minutes to form 8 ml of gel-type plasma.
  • Step 7 Mecroneedle Therapy (MTS) for the affected area
  • Step 8 Inject the (a) gel-type plasma and the mixed solution of PRP and bFGF and (b) the PRP and bFGF solution sequentially into the microneedle treated area.
  • Step 9 Repeat the treatment from Step 1 to Step 8 at least twice for 4 months
  • FIG. 3A shows the condition of the lesion before the first treatment
  • FIG. 3B shows the condition of the lesion four months after the first treatment.
  • the patient in Case 1 is Hamilton-Norwood Phase III androgen alopecia, androgenetic alopecia.
  • the patient's hair loss began several years ago. After repeated treatments in the affected area, once every month for four months, the patient's hair density increased from 5% to 43%.
  • Step 3- The plasma from step 2 was placed in a sterile container and submerged in 100 ° C. water for 5 minutes to form 12 ml of gel-type plasma.
  • Step 7 Mecroneedle Therapy (MTS) for the affected area
  • Step 8 Inject the mixture of (a) gel-type plasma and a mixture of PRP and bFGF and (b) a mixture of PRP and bFGF into the microneedle
  • Step 9 Repeat the treatment from step 1 to step 8 again
  • FIG. 4A shows the condition of the lesion before the first treatment and FIG. 4B shows the condition of the lesion after 56 days after the first treatment.
  • the patient in Case 2 is a male with androgen alopecia of stage 4 of Hamilton-Norwood, who started hair loss about five years ago. After two treatments the affected hair density increased from 5% (FIG. 4A) to 49% (FIG. 4B). 4B is 56 days after the first treatment, and the third treatment of the patient is also going on.
  • Hair condition before treatment hair loss of both temporal heads due to previous radiation treatment
  • Step 3- The plasma from step 2 was placed in a sterile container and submerged in 100 ° C. water for 5 minutes to form 4 ml of gel-type plasma.
  • Step 7 Mecroneedle Therapy (MTS) for the affected area
  • Step 8 Inject the mixture of (a) gel-type plasma with PRP and bFGF and (b) PRP and bFGF
  • Step 9 Repeat the treatment from step 1 to step 8 again
  • 5A and 5B show the state of the left head and the right head before treatment.
  • 5C and 5D show the lesions 56 days after the first treatment.
  • the patient in Case 3 was a woman who had received radiation treatment at the site five years ago because of a left temporal lobe tumor. Hair loss in the left head was more advanced than in the right head. At 56 days after receiving two treatments at four week intervals, the hair density of the lesions increased from 3% (FIGS. 5A and 5B) to 43% (FIGS. 5C and 5D).
  • Step 3- The plasma from step 2 was placed in a sterile container and submerged in 100 ° C. water for 5 minutes to form 12 ml of gel-type plasma.
  • Step 4 Preparing 100 ⁇ g / ml bFGF solution by dissolving 500 ⁇ g of bFGF lyophilized product in 5 ml of saline.
  • Step 7 Mecroneedle Therapy (MTS) for the affected area
  • Step 8 Inject the (a) gel-type plasma and a mixture of PRP and bFGF and (b) PRP and bFGF
  • Step 9 Repeat the treatments from Step 1 to Step 8 two more times, four weeks apart
  • FIG. 6A shows the condition of the lesion before the first treatment
  • FIG. 6B shows the condition of the lesion 56 days after the first treatment.
  • Case 4 The patient in Case 4 is a male with a Hamilton-Norwood stage 4 alopecia, whose hair has begun about 25 years ago. After three months of treatment every four weeks, the affected hair density increased from 6% (Figure 6A) to 49% ( Figure 6B). One month after the first treatment, the patient noticed hair growth and thickened hair stems.
  • Step 3- The plasma from step 2 was placed in a sterile container and submerged in 100 ° C. water for 5 minutes to form 4 ml of gel-type plasma.
  • step (a) gel-type plasma (4 ml) and bFGF solution (0.5 ml) and solution of step (b) (0.5 ml),
  • Step 7 Mecroneedle Therapy (MTS) for the affected area
  • Step 8 Inject the (a) gel-type plasma and a mixture of PRP and bFGF and (b) PRP and bFGF
  • FIG. 7A shows the condition of the affected lesion before the first treatment
  • FIG. 7B shows the condition of the lesion 56 days after the first treatment.
  • the patient in Case 5 was a woman with alopecia areata with a Luwing wing classification stage I-3 and started to lose hair about a year ago. After two treatments at four-week intervals, the hair density of the lesions increased from 0% before treatment (FIG. 7A) to 59% (FIG. 7B) 56 days after the first treatment day.
  • Table 1 Graph showing hair change before and after treatment case gender age Scalp condition Number of treatments Hair density Before treatment After treatment Case 1 male 52 years old Hamilton-Norwood 3-stage Integer Hair Loss 3 5% 43% Case 2 male 45 years old Hamilton-Norwood Stage 4 2 5% 49% Case 3 female 44 years old Hair Loss Due to Radiation Therapy 2 3% 43% Case 4 male 67 years old Hamilton-Norwood 4-stage M-shaped hair loss 3 6% 49% Case 5 female 37 years old Ludwing Classifications I-3 Stage Alopecia areata 2 0% 59%
  • FIG. 8A is a graph showing the hair density change of the cases
  • FIG. 8B is a graph showing the average of the hair density change of the cases.
  • the average hair density of the patients before treatment was less than 5% but increased by more than 45% after one to three treatments.
  • composition according to the invention can stimulate and promote hair growth and prevent unwanted hair loss.
  • compositions of the present invention and methods for their preparation, as well as methods of treatment can be quantitatively treated to patients on a mass-producible basis, of course, with industrial applicability.

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Abstract

La présente invention concerne un procédé servant à favoriser la pousse des cheveux et à empêcher la chute des cheveux d'un patient, une composition associée et un procédé de préparation de la composition. Plus particulièrement, le procédé servant à favoriser la pousse des cheveux et à empêcher la chute des cheveux d'un patient est caractérisé en ce qu'une composition contenant une quantité efficace d'un ingrédient actif comprenant du bFGF est administrée par voie intradermique ou sous-cutanée à une lésion d'un patient souffrant de chute des cheveux. Le procédé servant à favoriser la pousse des cheveux et à empêcher la chute des cheveux d'un patient, la composition associée et le procédé de préparation de la composition de la présente invention ont pour effet la formation de nouveaux vaisseaux sanguins au niveau d'une lésion afin d'augmenter l'alimentation de sang, et la croissance des tissus de fibres et la régénération des tissus sont favorisées, épaississant ainsi le tissu de la peau d'une lésion.
PCT/KR2015/004633 2015-03-23 2015-05-08 Procédé pour favoriser la pousse des cheveux et empêcher la chute des cheveux d'un patient, composition associée et procédé de préparation de la composition Ceased WO2016153103A2 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP2016576075A JP6823463B2 (ja) 2015-03-23 2015-05-08 患者の毛髪成長促進及び脱毛予防のための方法、並びにこのための組成物とその製造方法
BR112017020132A BR112017020132A2 (pt) 2015-03-23 2015-05-08 métodos para promover o crescimento capilar ou prevenir a perda de cabelo em um indivíduo e para preparar uma composição, e, composição
MX2017012125A MX2017012125A (es) 2015-03-23 2015-05-08 Metodo para promover crecimiento capilar e impedir perdida capilar de paciente, composicion para el mismo, y metodo para preparar composicion.
CA2979822A CA2979822C (fr) 2015-03-23 2015-05-08 Procede pour favoriser la pousse des cheveux et empecher la chute des cheveux d'un patient, composition associee et procede de preparation de la composition
RU2017132712A RU2690845C2 (ru) 2015-03-23 2015-05-08 Способ для стимулирования роста волос и предотвращения выпадения волос пациента, вещество для него и способ получения вещества
AU2015388056A AU2015388056B2 (en) 2015-03-23 2015-05-08 Method for promoting hair growth and preventing hair loss of patient, composition therefor, and method for preparing composition
EP15886551.9A EP3275459A4 (fr) 2015-03-23 2015-05-08 Procédé pour favoriser la pousse des cheveux et empêcher la chute des cheveux d'un patient, composition associée et procédé de préparation de la composition
CN201580078177.6A CN107708721A (zh) 2015-03-23 2015-05-08 促进头发生长及预防脱发的方法及组合物与制造方法

Applications Claiming Priority (4)

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US14/665,740 US9173921B1 (en) 2015-03-23 2015-03-23 Method of promoting hair growth by administration of bFGF
US14/665,740 2015-03-23
KR1020150059960A KR101738536B1 (ko) 2015-03-23 2015-04-28 모발 성장 촉진용 염기성 섬유모세포 생장인자 조성물 및 그 제조 방법
KR10-2015-0059960 2015-04-28

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Cited By (1)

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Publication number Priority date Publication date Assignee Title
CN119015209A (zh) * 2024-10-28 2024-11-26 温州医科大学附属第一医院 一种负载聚乙烯吡咯烷酮修饰的铱纳米颗粒和碱性成纤维细胞生长因子的微针及应用

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KR100796817B1 (ko) * 2005-03-23 2008-01-22 정용지 모발과 피부의 치료를 위한 성장인자
US20080193386A1 (en) * 2005-03-24 2008-08-14 Medigenes Co., Ltd Compositions for Treating Alopecia or Promoting Hair Growth

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119015209A (zh) * 2024-10-28 2024-11-26 温州医科大学附属第一医院 一种负载聚乙烯吡咯烷酮修饰的铱纳米颗粒和碱性成纤维细胞生长因子的微针及应用

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