Sebum secretion inhibitors

Abstract

To provide a sebum secretion inhibitor with high safety and therapeutic efficacy. [Solution] A sebum secretion inhibitor containing TEMPOL or a salt thereof as an active ingredient. A sebum secretion inhibitor containing 0.01 to 3% w / v of TEMPOL or a salt thereof. A sebum secretion inhibitor administered orally or applied topically to the skin. A sebum secretion inhibitor administered by injection. A sebum secretion inhibitor contained in a beverage or drinking water. A sebum secretion inhibitor contained in a cosmetic used on the skin.

Description

Technical Field

[0001] The present invention relates to a sebum secretion inhibitor.

Background Art

[0002] Acne (acne vulgaris) is an inflammatory disease centered around the hair follicles that enclose the hair roots. Normally, sebum is secreted by sebaceous glands in the hair follicles, but when the secretion of sebum becomes excessive, it may cause a state where sebum accumulates in the hair follicles (white acne). When acne further progresses, the growth of acne bacteria in the sebum accumulated in the hair follicles causes inflammation of the hair follicles (red acne). Acne mainly occurs on the face, and if left untreated, it is likely to cause aesthetic problems because it leaves scars and keloids.

[0003] As one of the therapeutic agents for acne, there is isotretinoin, which is mainly composed of a vitamin A derivative, retinoid. Isotretinoin has the effect of suppressing sebum secretion and is used for the treatment of severe acne. However, isotretinoin has a risk of serious side effects such as teratogenicity and has problems with safety. Therefore, there has been a demand for an effective sebum secretion inhibitor with higher safety than isotretinoin for patients suffering from sebum secretion.

[0004] On the other hand, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (hereinafter, TEMPOL) is an organic compound represented by the molecular formula C9H 18 NO2. Conventional uses of TEMPOL include oxidants and catalysts. In biochemistry, TEMPOL is known to have the effect of detoxifying reactive oxygen species such as superoxide, hydrogen peroxide, and hydroxyl radicals. As a literature verifying the effect of TEMPOL as a pharmaceutical, there is Non-Patent Document 1.

Prior Art Documents

Non-Patent Documents

[0005]

Non-Patent Document 1

[0006] Non-patent document 1 reported that intravenous administration of TEMPOL to a hypertensive model mouse resulted in a rapid and reversible dose-dependent decrease in blood pressure. However, no effects of TEMPOL on the body surface, such as the skin, had been reported. In particular, no effects that could be considered useful for preventing or treating acne, such as sebum suppression, had been reported until now.

[0007] The present invention has been made in view of the above circumstances, and its purpose is to provide a sebum secretion inhibitor that has high safety and therapeutic effect. [Means for solving the problem]

[0008] To solve the above problems, the present invention has the following aspects. [1] A sebum secretion inhibitor containing TEMPOL or a salt thereof as an active ingredient. [2] A sebum secretion inhibitor according to [1], comprising 0.01 to 3% w / v of the aforementioned TEMPOL or a salt thereof. [3] A sebum secretion inhibitor according to [1] or [2], administered orally or topically to the skin. [4] A sebum secretion inhibitor according to [1] or [2], administered by topical application to the skin. [5] A sebum secretion inhibitor according to [1] or [2], administered by injection. [6] A sebum secretion inhibitor contained in a beverage or drinking water, relating to [1] or [2]. [7] A sebum secretion inhibitor according to [1] or [2], contained in cosmetics used on the skin. [8] A sebum secretion inhibitor contained in sunscreen, relating to [7]. [9] An acne treatment agent, a sebum secretion inhibitor according to [1] or [2].

[10] A sebum secretion inhibitor relating to [1] or [2], which is used for the treatment of seborrhea.

[11] A sebum secretion inhibitor relating to [1] or [2], which is a body odor inhibitor.

[12] A dandruff preventative, which is a sebum secretion inhibitor related to [1] or [2]. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide a sebum secretion inhibitor with high safety and therapeutic effect. [Brief explanation of the drawing]

[0010] [Figure 1] Figure 1 is a graph showing the area of ​​sebum deposition on the back of rats administered TEMPOL (TEMPOL group) and control rats (control group). [Figure 2] Figure 2 shows photographs of representative samples from the TEMPOL group and the control group. [Figure 3] Figure 3 is a graph comparing body weight and marker gene expression levels in the TEMPOL group and the control group. [Figure 4] Figure 4 shows photographs of a rat model of excessive sebum production before and after administration of TEMPOL. [Modes for carrying out the invention]

[0011] One embodiment of the present invention will be described below. The embodiments shown below illustrate configurations for realizing the technical idea of ​​the present invention, and the present invention is not limited to the embodiments shown below. Various modifications can be made to the technical idea of ​​the present invention within the technical scope defined by the claims described in the claims.

[0012] (Sebum secretion inhibitor) The sebum secretion inhibitor in this embodiment contains TEMPOL or its salt as an active ingredient, and is a sebum secretion inhibitor for administration and treatment to a subject showing symptoms of a disease caused by excessive sebum secretion such as acne.

[0013] TEMPOL (C9H 18 NO2, CAS number: 2226-96-2) is known as a stable radical, and it has been reported that it promotes the decomposition of active oxygen as a pharmaceutical.

[0014] As the salt of TEMPOL, any pharmaceutically acceptable salt can be appropriately selected. Also, within the pharmaceutically and physiologically acceptable range and within the range that does not reduce the pharmacological effect, various derivatives of TEMPOL can be selected.

[0015] The sebum secretion inhibitor of this embodiment is a sebum secretion inhibitor for administration and treatment to a subject showing symptoms of a disease caused by excessive sebum secretion. Such diseases include, for example, acne, seborrhea, abnormal body odor, and dandruff. The sebum secretion inhibitor of this embodiment can be used as an acne treatment drug and a treatment drug for these diseases.

[0016] Acne is an inflammatory disease centered around the hair follicles that surround the hair roots. Usually, sebum is secreted by the sebaceous glands in the hair follicles, but when the secretion of sebum becomes excessive, it may cause a state where sebum accumulates in the hair follicles (white acne). When acne progresses further, the growth of acne bacteria in the sebum accumulated in the hair follicles causes inflammation of the hair follicles (red acne). The sebum secretion inhibitor of this embodiment is also effective for acne treatment. Also, the sebum secretion inhibitor of this embodiment has fewer side effects compared to the prior art.

[0017] The sebum secretion inhibitor of this embodiment is also effective for seborrhea treatment, body odor suppression, and dandruff prevention. For these diseases, the sebum secretion inhibitor of this embodiment shows an effect by suppressing the secretion of excessive sebum. Also, the sebum secretion inhibitor of this embodiment has fewer side effects compared to the prior art.

[0018] The subjects exhibiting symptoms of excessive sebum secretion, such as acne, that are the target of this embodiment can be appropriately selected from humans and other animals. Other animals mainly include mammals. Specifically, mammals include domestic animals (pigs, sheep, goats, cattle, horses, etc.), companion animals (dogs, cats, etc.), laboratory animals (mice, guinea pigs, hamsters, rats, other rodents, rabbits, etc.), and other animals (marmosets, chimpanzees, other monkeys). In this specification, the term "patient" mainly refers to human subjects, but is not limited to humans.

[0019] The purpose of administering the sebum secretion inhibitor of this embodiment to patients with acne or the like broadly includes medical treatment purposes such as treatment, prevention, and prevention of recurrence after treatment. As will be described later, treatment may include, but is not limited to, oral administration.

[0020] The sebum secretion inhibitor of this embodiment preferably contains 0.01 to 3% w / v of TEMPOL or a salt thereof when administered orally. More preferably 0.04 to 1.5% w / v, and even more preferably 0.06 to 0.75% w / v. When administered topically, 0.01 to 3% w / v is preferred, and more preferably 0.1 to 3% w / v. When administered by injection, 0.01 to 1% w / v is preferred, and more preferably 0.1 to 1% w / v.

[0021] (Oral medication) The sebum secretion inhibitor of this embodiment may be an oral liquid formulation. The oral liquid formulation of the sebum secretion inhibitor is preferably a formulation suitable for oral administration. The concentration can be appropriately selected from the concentration of the sebum secretion inhibitor described above. In addition to the sebum secretion inhibitor, the oral liquid formulation of this embodiment may contain pharmaceutically acceptable optional components, provided that they do not impair the effects of the configuration of this embodiment.

[0022] (Other pharmaceuticals) The sebum secretion inhibitor of this embodiment may be a topical agent applied to the skin. In addition to the above, these may contain ingredients similar to those found in general skin ointments. These topical agents may be in the form of a liquid, lotion, emulsion, spray, cream, or gel. They may also be in the form of other topical products such as lotions, serums, or sunscreens.

[0023] (aqueous solution) The sebum secretion inhibitor of this embodiment may be an aqueous solution. These aqueous solutions may be in the form of beverages, supplements, or cosmetics, and may contain the same ingredients as general beverages, supplements, and cosmetics.

[0024] The administration conditions for the sebum secretion inhibitor in this embodiment may be appropriately selected depending on the form of the therapeutic agent, as well as the patient's symptoms, weight, age, and sex.

[0025] The sebum secretion inhibitor of this embodiment can be widely used for the aforementioned purposes, specifically for administering and treating subjects exhibiting symptoms such as acne.

[0026] (Effects of this embodiment) According to this embodiment, it is possible to provide a sebum secretion inhibitor that has higher safety and therapeutic effect compared to the conventional technology.

[0027] The inventors discovered that oral administration of TEMPOL suppresses sebum secretion. Furthermore, the active ingredient of this embodiment was also effective against excessive sebum secretion.

[0028] Conventionally, TEMPOL has been widely known to promote the detoxification of reactive oxygen species and to have a certain effect on lowering blood pressure. However, its effect on improving sebum secretion and acne was unknown. This embodiment differs from the previously known effects in that it has an inhibitory effect on sebum secretion, and oral administration of TEMPOL can improve the symptoms of acne patients.

[0029] This embodiment also includes, in other respects, the following aspects. Another aspect of this embodiment is a method for producing the sebum secretion inhibitor. Another aspect of this embodiment is the use of TEMPOL to produce the sebum secretion inhibitor. Another aspect of this embodiment is the use of a sebum secretion inhibitor for the treatment of acne and the like. Another aspect of this embodiment is the use of TEMPOL for use in the treatment of acne and the like. Another aspect of this embodiment is a method for treating acne and the like using the sebum secretion inhibitor. Another aspect of this embodiment is a method for treating acne and the like using the sebum secretion inhibitor.

[0030] Although embodiments of the present invention have been described above, the present invention is not limited to the above embodiments and can be modified in various ways. [Examples]

[0031] (Suppression of sebum secretion by oral administration) Twelve-week-old Wistar rats were divided into a TEMPOL group and a control group. The TEMPOL group rats were given an ad libitum of water containing TEMPOL dissolved in ultrapure water to a concentration of 1 mM for eight weeks. The control group rats were given water without TEMPOL for eight weeks. Subsequently, the area of ​​sebum deposition on the backs of the rats was compared between the TEMPOL group and the control group.

[0032] Figure 1 shows the area of ​​sebum deposition on the back in the TEMPOL group and the control group. The vertical axis represents the sebum deposition area (%), with the left side representing the control group and the right side representing the TEMPOL group. While sebum deposition on the back spontaneously occurs in rats, the TEMPOL group showed a significantly reduced area of ​​sebum deposition compared to the control group (p<0.0001), indicating that sebum secretion was suppressed.

[0033] Figure 2 shows the results of photographing the median samples from the TEMPOL group and the control group. The left side shows the control group, and the right side shows the TEMPOL group. It was confirmed that sebum accumulation was suppressed in the TEMPOL group compared to the control group, which was identifiable even with the naked eye.

[0034] (Safety check) To confirm the presence of side effects from TEMPOL administration, post-experimental body weight and liver inflammation marker gene expression were measured in rats from both the TEMPOL group and the control group. The results are shown in Figure 3.

[0035] The measurement results showed no significant differences in body weight or the expression of liver inflammation marker genes between the TEMPOL group and the control group. Based on these results, it was inferred that oral administration of TEMPOL has very few side effects.

[0036] (Experiments using a rat model with excessive sebum production) The inventors have empirically confirmed that rats develop excessive sebum on their backs as they age. Using this, they conducted experiments with aged rats over one year old as a model rat for excessive sebum, under the same conditions as the oral administration experiment of TEMPOL described above, and compared the area of ​​sebum deposition on the back before and after the experiment. The results are shown in Figure 4.

[0037] The image on the left shows a rat model of excessive sebum production before drinking TEMPOL, and the image on the right shows a rat model of excessive sebum production after drinking TEMPOL. The experimental results confirmed that a reduction in the area of ​​sebum deposition was visible to the naked eye even in rats modeling excessive sebum production.

[0038] The above experiments experimentally confirmed that drinking TEMPOL can effectively suppress sebum secretion, and that drinking TEMPOL has virtually no side effects. Since "excessive sebum secretion" is one of the causes of acne in humans, it is presumed that TEMPOL can effectively suppress acne development by suppressing sebum secretion. Furthermore, TEMPOL has not been found to be listed as a poison, and it showed high safety in this experiment, so it is presumed to be safer than conventional technologies.

Claims

1. A sebum secretion inhibitor containing TEMPOL or a salt thereof as an active ingredient.

2. The sebum secretion inhibitor according to claim 1, comprising 0.01 to 3% w / v of TEMPOL or a salt thereof.

3. An oral sebum secretion inhibitor according to claim 1 or 2.

4. A sebum secretion inhibitor according to claim 1 or 2, administered by topical application to the skin.

5. A sebum secretion inhibitor according to claim 1 or 2, administered by injection.

6. A sebum secretion inhibitor according to claim 1 or 2, contained in a beverage or drinking water.

7. A sebum secretion inhibitor according to claim 1 or 2, which is contained in cosmetics used on the skin.

8. A sebum secretion inhibitor according to claim 7, which is contained in sunscreen.

9. An acne treatment agent, the sebum secretion inhibitor according to claim 1 or 2.

10. A sebum secretion inhibitor according to claim 1 or 2, which is a treatment for seborrhea.

11. A sebum secretion inhibitor according to claim 1 or 2, which is a body odor inhibitor.

12. A sebum secretion inhibitor according to claim 1 or 2, which is a dandruff preventative.

Images