Novel pharmaceutical and method for hair growth or restoration

Abstract

To provide novel pharmaceuticals, combination agents, and preparations for hair growth and / or restoration.SOLUTION: A pharmaceutical composition for the growth and / or restoration of the hair and the like includes a pharmaceutically effective amount of oxytocin, and a pharmaceutically acceptable carrier. The pharmaceutical composition optionally further contains one or more KATP channel opener.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a novel pharmaceutical composition, agent, method, etc. for promoting hair growth and / or hair development, and a method therefor. Specifically, the present invention relates to a novel pharmaceutical composition, agent, method, etc. comprising oxytocin and, optionally, a KATP channel opener as active ingredients. [Background technology]

[0002] Oxytocin is currently used as an injectable labor-promoting drug. However, in recent years, it has been discovered that oxytocin has an appetite-suppressing effect, and therefore has the effect of improving diseases such as obesity and metabolic syndrome (Non-Patent Documents 1 to 3). Oxytocin is also known to have the effect of improving mental disorders such as autism, schizophrenia, and depression (Non-Patent Document 2).

[0003] However, to date, no medicine for promoting hair growth and / or hair development using oxytocin as an active ingredient has been known. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Maejima Y et al., AGING, December 2011, Vol, 3, No. 12 [Non-patent document 2] Maejima Y et al., Neuroendocrinology DOI: 10.1159 / 000371636 [Non-patent document 3] Maejima Y et al., Scientific Reports, DOI: 10.1038 / s41598-017-09318-7 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a novel medicament and method for hair growth and / or hair development. [Means for solving the problem]

[0006] The present inventors have now discovered for the first time that oxytocin receptors are present in hair roots and hair matrix cells. Based on this finding, they have discovered for the first time that administering oxytocin alone, or optionally in combination with a KATP channel opener, as an active ingredient can express these oxytocin receptors and observe hair growth and / or hair development, thereby completing the present invention. Specifically, the present invention provides a pharmaceutical composition for hair growth and / or hair development, comprising a pharmaceutically effective amount of oxytocin, optionally a pharmaceutically effective amount of a KATP channel opener, and a pharmaceutically acceptable carrier. Thus, the pharmaceutical composition of the present invention makes it possible to provide novel medicaments and methods for hair growth and / or hair development.

[0007] That is, the present invention includes the following aspects, but is not limited to these.

[0008] (Pharmaceutical composition) Item [1] A pharmaceutical composition for hair growth and / or hair development, comprising a pharmaceutically effective amount of oxytocin and a pharmaceutically acceptable carrier. Item [2] The pharmaceutical composition according to item [1], further comprising a pharmaceutically effective amount of one or more KATP channel openers. Item [3] The pharmaceutical composition according to item [2], wherein the KATP channel opener is one or more compounds selected from the group consisting of nicorandil, minoxidil, and diazoxide. Item [4] The pharmaceutical composition according to any one of items [1] to [3], wherein at least one of the pharmaceutically acceptable carriers is a skin-penetrating agent. Item [5] The pharmaceutical composition according to any one of items [1] to [4], wherein the skin penetration agent is one or more compounds selected from the group consisting of methylglyoxal and propylene glycol. Item [6] The pharmaceutical composition according to any one of items [1] to [5], for promoting hair growth and / or hair development.

[0009] (Combination drug) The present invention also includes the following aspects, but is not limited to these. Item [7] A first agent comprising a pharmaceutically effective amount of oxytocin as an active ingredient and a pharmaceutically acceptable carrier; and a second agent comprising a pharmaceutically effective amount of one or more KATP channel openers as active ingredients and a pharmaceutically acceptable carrier; A drug for hair growth and / or hair restoration, comprising a combination of: Item [8] The drug according to Item [7], wherein the KATP channel opener is one or more compounds selected from the group consisting of nicorandil, minoxidil, and diazoxide. Item [9] The drug according to either item [7] or item [8], wherein at least one of the pharmaceutically acceptable carriers in the first drug and / or the second drug is a skin-penetrating agent. Item

[10] The agent according to any one of items [7] to [9], wherein the skin penetration agent is one or more compounds selected from the group consisting of methylglyoxal and propylene glycol. Item

[11] The first drug containing oxytocin is administered simultaneously with, before, or after the administration of a second drug containing one or more KATP channel openers. The drug according to any one of items [7] to

[10] .

[0010] (formulation) Item

[12] A pharmaceutical preparation for a subject in need of treatment, comprising a pharmaceutical composition according to any one of items [1] to [6] or a drug according to any one of items [7] to

[11] . Item

[13] The pharmaceutical preparation according to item

[12] , which is a skin external preparation. Item [13-2] The pharmaceutical preparation according to item

[13] , wherein the topical skin preparation is a topical liquid, ointment, cream, lotion, or spray.

[0011] Item

[14] The pharmaceutical preparation according to item

[12] , wherein the subject is a human. Item

[15] The pharmaceutical preparation according to Item

[14] , wherein the subject is a human suffering from baldness or baldness disease.

[0012] (method) The present invention also includes the following aspects, but is not limited to these. Item

[16] A method for hair growth and / or hair development, comprising administering to a subject a pharmaceutically effective amount of oxytocin, and optionally a pharmaceutically effective amount of one or more KATP channel openers.

[17] The method according to

[16] , wherein the subject is a human.

[18] The method according to

[16] or

[17] , wherein the subject is a human suffering from baldness or a baldness disease.

[0013] (use) Item

[19] Use of a pharmaceutically effective amount of oxytocin alone or in combination with a pharmaceutically effective amount of one or more KATP channel openers to manufacture a formulation for hair growth and / or hair development in a subject. Item

[20] Use of a pharmaceutically effective amount of oxytoxi alone or in combination with a pharmaceutically effective amount of one or more KATP channel openers for hair growth and / or hair development in a subject. [Effects of the Invention]

[0014] The use of oxytocin as an active ingredient of the present invention, alone or in combination with one or more KATP channel openers, can produce significant effects in promoting hair growth and / or hair development. [Brief explanation of the drawings]

[0015] [Figure 1]Figure 1 shows the results of an investigation into the hair growth promoting effect when shaved mice were administered a test solution containing oxytocin or when no oxytocin was administered (i.e., when a control test solution not containing oxytocin was administered). DETAILED DESCRIPTION OF THE INVENTION

[0016] (definition) The term "oxytocin" as used herein refers to a peptide hormone composed of nine amino acids. While receptor expression has been confirmed in the uterus, mammary gland, kidney, heart, thymus, pancreas, and adipose tissue, its expression in hair matrix and hair root cells has not been reported. The inventors of this application have now discovered, for the first time, the presence of oxytocin receptors in hair matrix and hair root cells.

[0017] As used herein, the term "KATP channel opener" refers to an ATP-sensitive K + This refers to a channel. It is also known to be a vasodilator, and is therefore expected to have a significant effect on hair growth and / or hair development. Specific examples of KATP channel openers used in the present invention include diazoxide, minoxidil, and nicorandil, with nicorandil being preferred.

[0018] The pharmaceutically effective amount of oxytocin used in the present invention is not limited unless otherwise specified, but may be, for example, 0.01 mg to 1 mg per kg of patient body weight per day.

[0019] The pharmaceutically effective amount of the KATP channel opener used in the present invention is not limited unless otherwise specified, but can be, for example, 0.01 mg to 1 mg per day as the total amount of one or more KATP channel openers per kg of patient body weight.

[0020] The pharmaceutical composition of the present invention comprises a pharmaceutically effective amount of oxytocin, a pharmaceutically acceptable carrier, and, optionally, a pharmaceutically effective amount of one or more KATP channel openers. Preferably, a pharmaceutically effective amount of one or more KATP channel openers is included in the pharmaceutical composition of the present invention.

[0021] According to one embodiment of the present invention, when the pharmaceutical composition of the present invention is administered to a subject (e.g., a human), the pharmaceutical composition may be administered 1 to 10 times, 1 to 5 times, 1 to 3 times, 1 to 2 times, or once per day. Alternatively, the pharmaceutical composition of the present invention may be administered 1 to 3 times, 1 to 2 times, or once per day within several days, or 1 to 3 times, 1 to 2 times, or once per week, or 1 to 3 times, 1 to 2 times, or once per week (e.g., 2 to 3 weeks). The number of administrations may be adjusted taking into consideration the effects after administration or side effects (e.g., inflammation).

[0022] According to one aspect of the present invention, when the pharmaceutical composition of the present invention is administered to a subject (e.g., a human), the pharmaceutical composition may be administered for several days, several weeks, several months, several years, or even several decades. The administration period may be adjusted taking into consideration the number of administrations, the effects after administration, or side effects (e.g., inflammation). Depending on the effect achieved, the administration period may be varied as appropriate, for example, for several weeks, several months, several years, or several decades, preferably for several weeks, several months, or several years. Administration may also be resumed after a certain period of suspension.

[0023] The pharmaceutical composition, drug, or pharmaceutical preparation of the present invention comprises a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may vary depending on the dosage form used, but may include carriers commonly used in formulations. For example, when the pharmaceutical composition, drug, or pharmaceutical preparation of the present invention is used as an external preparation for skin (e.g., ointment, cream, external liquid), the pharmaceutically acceptable carrier may include surfactants (including anionic, nonionic, cationic, and amphoteric surfactants), higher fatty acids, oils and fats, pH stabilizers, antioxidants, chelating agents, solvents, etc., or combinations of two or more of these substances, such as pharmaceutically acceptable carriers commonly used in known compositions, drugs, or pharmaceutical preparations for hair.

[0024] The pharmaceutically acceptable carrier used in the present invention preferably includes a skin penetrating agent.Skin penetrating agent refers to a component that promotes the penetration of the active ingredient of the present invention into the skin (for example, scalp) or hair.Examples of the penetrating agent include amines, alcohols, surfactants, etc., or the combination of two or more of these substances. Specific examples of amines include urea, alcohol amines (e.g., monoethanolamine, etc.), and combinations of two or more of these substances. Specific examples of alcohols include, but are not limited to, lower alcohols (e.g., ethanol), higher alcohols (e.g., stearyl alcohol and lauryl alcohol), and polyhydric alcohols (e.g., ethylene glycol and methylglyoxal). Specific examples of skin-penetrating agents include alcohols, preferably polyhydric alcohols, and more preferably one or more compounds selected from the group consisting of propylene glycol and methylglyoxal. For example, the ratio of propylene glycol and methylglyoxal to the active ingredient of the present invention may be adjusted to achieve optimal skin penetration.

[0025] According to one embodiment of the present invention, the weight ratio of methylglyoxal or propylene glycol to the total weight of the pharmaceutical composition is, but is not particularly limited to, in the range of 0.1 to 10%.

[0026] The mechanism of hair growth is thought to be that, under the control of hair papilla cells, hair matrix cells use oxygen and / or nutrients delivered from the capillaries as energy, repeatedly proliferate and / or differentiate, and this process leads to hair growth. More specifically, oxytocin stimulates oxytocin receptors on the surface of hair matrix cells, promoting hair growth. Furthermore, as mentioned above, KATP channel openers, known as vasodilators, stimulate hair matrix cells from the hair papilla with VEGF (vascular endothelial growth factor) or IGF-1 (insulin-like growth factor), which increases blood flow and promotes hair growth. Therefore, the overall mechanism of hair growth and growth involves oxytocin and KATP channel openers stimulating hair matrix cells with VEGF or IGF-1 produced by the hair papilla, and the increased blood flow caused by KATP channel openers increases the supply of oxygen and nutrients, promoting hair growth in a rational manner. Additionally, skin penetration agents are optionally used to increase and optimize penetration of the agent (eg, oxytocin or KATP channel opener) into the skin (eg, scalp).

[0027] When the pharmaceutical composition of the present invention is administered (e.g., applied) to a subject, it may be provided to the subject in the form of a pharmaceutical composition containing a skin penetration agent, or the skin penetration agent may be provided to the subject before, simultaneously with, or after administering (e.g., applying) the pharmaceutical composition. Providing the skin penetration agent beforehand is preferred.

[0028] The hair to be grown and cared for in the present invention includes hair on the entire body, particularly human scalp hair, and also includes hair on both male and female scalps, more preferably male scalp hair.

[0029] (Combination drug) The present invention can use oxytocin as an active ingredient in combination, ie, in conjunction, with one or more KATP channel openers.

[0030] According to one embodiment of the present invention, The agent for hair growth and / or hair development of the present invention is a first agent comprising a pharmaceutically effective amount of oxytocin as an active ingredient and a pharmaceutically acceptable carrier; and a second agent comprising a pharmaceutically effective amount of one or more KATP channel openers as active ingredients and a pharmaceutically acceptable carrier; Includes a combination of:

[0031] According to one embodiment of the present invention, the pharmaceutically effective amount of oxytocin in the combination drug is not limited unless otherwise specified, but may be, for example, 0.01 mg to 1 mg per kg of patient body weight per day.

[0032] The pharmaceutically effective amount of the KATP channel opener used in the present invention is not limited unless otherwise specified, but examples include a total amount of the compound used as a KATP channel opener of 0.01 mg to 1 mg per kg of patient body weight per day.

[0033] According to one embodiment of the present invention, when oxytocin is used in combination with one or more KATP channel openers, the amount of oxytocin and the total amount of the one or more KATP channel openers may be in a weight ratio of 1:100 to 100:1, 1:50 to 50:1, 1:20 to 20:1, or 1:10 to 10:1 in terms of the blending amount or content.

[0034] According to one embodiment of the present invention, when the agent (i.e., combination) of the present invention is administered to a subject (e.g., a human), the agent (i.e., combination) may be administered 1 to 10 times, 1 to 5 times, 1 to 3 times, 1 to 2 times, or once per day. Alternatively, the pharmaceutical composition of the present invention may be administered 1 to 3 times, 1 to 2 times, or once within several days, or 1 to 3 times, 1 to 2 times, or once within a week, or 1 to 3 times, 1 to 2 times, or once within a few weeks (e.g., 2 to 3 weeks). Here, the number of administrations of the first agent containing oxytocin and the second agent containing a KATP channel opener may be the same or different. The number of administrations may be adjusted taking into account the post-administration effects or side effects (e.g., inflammation).

[0035] In the agents (ie, combination agents) of the present invention, a first agent comprising oxytocin may be administered simultaneously with, before, or after the administration of a second agent comprising one or more KATP channel openers.

[0036] The pharmaceutically acceptable carriers used in the agents (eg, combination agents) of the present invention are as described above in the pharmaceutical compositions.

[0037] (formulation) Unless otherwise specified, the term "pharmaceutical preparation" used herein includes either or both of the above pharmaceutical compositions and / or drugs.

[0038] According to one embodiment of the present invention, the pharmaceutical composition, combination, or pharmaceutical preparation of the present invention is formulated into a dosage form well known in pharmaceutical formulations, including, but not limited to, topical skin preparations. Examples of topical skin preparations include topical preparations, such as topical solutions, ointments, creams, lotions, and sprays.

[0039] When administering (e.g., applying) the agents (combinations) of the present invention to a subject, the skin penetration agent may be provided to the subject in the form of an agent contained in either or both of the first and second agents, or the skin penetration agent may be provided to the subject before, simultaneously with, or after administering (e.g., applying) the first and / or second agents. It is preferable to provide the skin penetration agent before administering both the first and second agents. When the skin penetration agent is not provided simultaneously with the first drug and / or the second drug, it is provided within a period of several seconds to several hours, preferably within a period of several seconds to several tens of minutes, and more preferably within a period of several seconds to several minutes.

[0040] Subjects to which the pharmaceutical use of the present invention can be applied include mammals (e.g., primates (e.g., humans), cows, pigs, sheep, goats, horses, dogs, cats, rabbits, mice, or rats, but are not limited to these), preferably humans, and more preferably people suffering from baldness or baldness.

[0041] The intended uses and / or effects of the present invention include hair growth and / or hair care in mammals (e.g., including pets and livestock, but particularly preferably humans) and hair (e.g., scalp hair is particularly preferred).

[0042] The pharmaceutical composition, combination, or pharmaceutical preparation of the present invention may further contain or be used in combination with other active substances for hair growth or hair restoration, if necessary. Such other active substances for hair growth or hair restoration may be, for example, known active substances, and specific examples include, but are not limited to, herbal medicines (e.g., Swertia japonica) and / or synthetic drugs (e.g., finasteride).

[0043] As used herein, "about" or "approximately" refers to an acceptable error for a particular value as determined by one of ordinary skill in the art, which error depends in part on how the value is measured or determined. In certain embodiments, the term "about" or "approximately" means within 1, 2, 3, or 4 standard deviations. For example, it means within 50%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, or 0.05% of a given value or range. [Example]

[0044] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples.

[0045] (Test Example 1) Hair growth and / or hair restoration tests After completely shaving the backs of mice (approximately 3 months to 1 year old), a composition containing 0.001% oxytocin in a predetermined amount of 0.9% propylene glycol was prepared. An appropriate amount of this composition was applied to the shaved area. A control group received only 0.9% propylene glycol (control) without oxytocin. The application was performed twice daily, in the morning (e.g., between 6:00 AM and 11:00 AM after waking up) and in the evening (e.g., between 4:00 PM and 11:00 PM), for 14 days. The two applications were separated by at least 6 hours, preferably at least 8 hours, to maximize the drug's effectiveness. As a result, it was confirmed that hair growth was significantly promoted in mice receiving the oxytocin-containing treatment.

[0046] The test results are shown in Figure 1. The group to which oxytocin was applied is designated as the "oxytocin group," and the observation results are shown in the upper part, and the group to which a control without oxytocin was applied is designated as the "control group," and the observation results are shown in the lower part. The day of shaving one day before application is abbreviated as "Day 0," the fourth day after application is abbreviated as "Day 4," the twelfth day after application is abbreviated as "Day 12," and the 15th day after 14 days of application is abbreviated as "Day 15." The observation results on the 12th and 15th days showed that almost no hair growth was observed in the control group, but significant hair growth was observed in the oxytocin group. This confirmed that oxytocin alone had a hair growth effect. [Industrial Applicability]

[0047] According to the present invention, a medicament that shows significant hair growth and / or hair development can be provided by using oxytocin alone or appropriately in combination with a KATP channel opener.

Claims

1. A pharmaceutical composition for hair growth and / or hair care comprising a pharma- ceutical effective amount of oxytocin and a pharma- ceutical acceptable carrier.

2. 10. The pharmaceutical composition of claim 1, further comprising a pharma- ceutically effective amount of one or more K ATP channel openers.

3. 3. The pharmaceutical composition of claim 2, wherein the K ATP channel opener is one or more compounds selected from the group consisting of nicorandil, minoxidil, and diazoxide.

4. 10. The pharmaceutical composition of claim 1, wherein at least one of the pharma- ceutically acceptable carriers is a skin-penetrating agent.

5. 5. The pharmaceutical composition of claim 4, wherein the skin penetration agent is one or more compounds selected from the group consisting of methylglyoxal and propylene glycol.

6. The pharmaceutical composition according to claim 1 for promoting hair growth and / or hair development.

7. a first agent comprising a pharma- ceutical effective amount of oxytocin as an active ingredient and a pharma- ceutical acceptable carrier; and a second agent comprising a pharma- ceutical effective amount of one or more K ATP channel openers as active ingredients and a pharma- ceutical acceptable carrier; A drug for hair growth and / or hair restoration comprising a combination of:

8. The method of claim 7, wherein the K ATP channel opener is one or more compounds selected from the group consisting of nicorandil, minoxidil, and diazoxide.

9. 8. The method of claim 7, wherein at least one of the pharma- ceutically acceptable carriers in the first and / or second agent is a skin-penetrating agent.

10. 10. The method of claim 9, wherein the skin penetrating agent is one or more compounds selected from the group consisting of methylglyoxal and propylene glycol.

11. The method of claim 7, wherein a first agent comprising oxytocin is administered simultaneously with, before, or after administration of a second agent comprising one or more K ATP channel openers.

12. A pharmaceutical formulation for a subject in need of treatment comprising the pharmaceutical composition of claim 1 or the agent of claim 7.

13. The pharmaceutical preparation according to claim 12, which is an external preparation for skin.

14. The pharmaceutical formulation of claim 12, wherein the subject is a human.

15. 15. The pharmaceutical formulation of claim 14, wherein the subject is a human suffering from baldness or baldness disease.