Application of rucotinib in prevention and treatment of androgenetic alopecia
By using ruxolitinib as a JAK inhibitor to counteract the hair follicle growth inhibition caused by dihydrotestosterone, the shortcomings of existing treatments for androgenetic alopecia have been overcome, achieving highly effective hair regeneration and providing a new treatment option for androgenetic alopecia.
Patent Information
- Application Number
- CN202511318011.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-16
- Publication Date
- 2025-12-16
AI Technical Summary
Existing treatments for androgenetic alopecia, such as minoxidil and finasteride, are inadequate in terms of effectiveness and safety. Furthermore, non-pharmacological treatments, such as PRP and microneedling, are complex or painful, leading to poor patient compliance. There is an urgent need for new, highly effective, and safe treatment options.
Ruxolitinib, as a JAK inhibitor, promotes hair regeneration by resisting the inhibition of hair follicle growth caused by dihydrotestosterone. It can be used in pharmaceuticals, daily chemical products, or food additives to intervene in or treat androgenetic alopecia.
Ruxolitinib can effectively combat hair loss caused by dihydrotestosterone and promote hair growth, providing a new treatment for androgenetic alopecia and showing significant hair regeneration effects.
Smart Images
Figure CN121129858A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of medicine, in particular to the application of relacorilant in the prevention and treatment of androgenetic alopecia. BACKGROUND
[0002] Androgenetic alopecia (AGA) is an androgen-dependent polygenic hereditary disease, and its typical manifestation is the shortening of the growth phase of hair follicles, leading to the shrinkage of hair follicles, the replacement of black and thick terminal hair with colorless and soft vellus hair, and the high atrophy of hair follicles and hair loss. AGA affects about 21.3% of men and 6% of women, and seriously affects the physical and mental health of patients.
[0003] Due to the increasing pressure in work, life and study in today's society, AGA shows a trend of youth, and the demand for hair loss treatment is increasing, and the method for treating AGA is also being developed. The main treatment methods for AGA include external application of minoxidil, oral administration of finasteride or spironolactone, hair transplantation surgery and low-density lipoprotein laser irradiation, and currently only two drugs, external minoxidil (promoting angiogenesis and dilating blood vessels) and oral finasteride (inhibiting 5-alpha reductase activity), have been approved by FDA for the treatment of AGA. However, a number of clinical studies have shown that these two treatment methods are not satisfactory in terms of effectiveness and safety. Many patients show poor compliance due to the need to use minoxidil twice a day, poor hair quality and propylene glycol contact dermatitis (propylene glycol is the main solvent of external minoxidil). The side effects of finasteride mainly include the impact on male sexual function, such as decreased libido and erectile dysfunction, as well as other symptoms such as depression, anxiety and male breast development. The efficacy of finasteride in treating female androgenetic alopecia is uncertain, and it may affect the estrogen level in the female body and have potential teratogenic effects. The classical treatment regimen for AGA has limitations, and most patients will continue to progress after stopping the drug, and even need to take the drug for life, so there is an urgent need for new treatment methods.
[0004] Non-pharmaceutical treatments such as PRP and microneedles are good treatment options, but the preparation process is relatively complex, some patients cannot tolerate the pain during the operation process, and some patients cannot accept blood products, which may not help severe AGA patients. There is not enough evidence to show that other commonly used drugs such as hormone drugs and over-the-counter supplements have efficacy on AGA. In addition, the multifactorial origin and chronic nature of AGA make it difficult to treat.
[0005] AGA causes serious psychological burden to patients, and leads to mental disorders in patients in the long run, and even depression in severe cases. Healthy and beautiful hair makes people more confident in the process of communication, so people's demand for hair loss treatment is becoming more and more urgent. Therefore, in this field, it is urgent to find more efficient and safe drugs for preventing and treating AGA to meet the clinical needs.
[0006] Ruxolitinib is a JAK inhibitor, which can be applied to the treatment of myelofibrosis, polycythemia vera and corticosteroid-refractory acute graft-versus-host disease. SUMMARY
[0007] Objective: In order to overcome the deficiencies in the prior art, the application provides an application of ruxolitinib in preventing and treating AGA, which has the effect of promoting hair regeneration and can resist hair loss caused by dihydrotestosterone.
[0008] To solve the above technical problems, the technical scheme adopted by the application is:
[0009] In a first aspect, the application provides an application of ruxolitinib in preventing and / or treating AGA.
[0010] Ruxolitinib can be applied to the treatment of myelofibrosis and polycythemia vera. The application of ruxolitinib to intervene in DHT-induced AGA model mice shows that ruxolitinib has the effect of promoting hair regeneration and can effectively resist hair loss caused by DHT. Based on this result, the application can provide a new method for preventing and / or treating AGA.
[0011] In the study of AGA patients, it is found that the JAK / STAT pathway of AGA patients is significantly activated, and this phenomenon is also observed in AGA animal models. Existing research shows that the activation of the JAK / STAT pathway may be related to the progress of AGA. Based on this result, the application further applies JAK inhibitor ruxolitinib to intervene in DHT-induced AGA model mice to determine the effect of ruxolitinib on AGA intervention, and expects to provide a new scheme for the prevention and / or treatment of AGA.
[0012] In some embodiments, the product includes a pharmaceutical product, a daily chemical product, a food product, or a food additive.
[0013] In some embodiments, the product is a pharmaceutical product, a daily chemical product, a food product, or a food additive for preventing and / or treating AGA by resisting dihydrotestosterone-induced inhibition of hair follicle growth.
[0014] In a second aspect, the application provides a product for treating AGA, wherein the active ingredient of the product includes ruxolitinib.
[0015] In some embodiments, the active ingredient of the product is luspatercept.
[0016] In some embodiments, the product is a pharmaceutical product, a daily chemical product, a food product, or a food additive.
[0017] In some embodiments, the product is a pharmaceutical product, a daily chemical product, a food product, or a food additive that prevents and / or treats androgenetic alopecia by resisting DHT-induced hair follicle growth inhibition.
[0018] In some embodiments, the daily chemical product includes hair care products and skin external use additives.
[0019] Beneficial effects: The luspatercept provided by the present application has the effect of promoting hair regeneration, can effectively resist DHT-induced hair loss, can be applied to prevent and / or treat androgenetic alopecia, and provides a new treatment scheme for preventing and / or treating androgenetic alopecia.
[0020] The present application discloses a method for preventing and / or treating androgenetic alopecia by resisting DHT-induced hair follicle growth inhibition, and provides a theoretical basis for intervention or / and treatment of androgenetic alopecia, and gives the feasibility of luspatercept in promoting hair regeneration. BRIEF DESCRIPTION OF DRAWINGS
[0021] Figure 1 Figure 1 is a graph showing the back hair growth of mice in Example 1 of the present application on the 0th day, 3rd day, 7th day, 10th day, 13th day, 16th day, and 19th day of the experiment.
[0022] Figure 2 Figure 2 is a graph showing the H&E staining observation and statistical results of the back skin of mice in Example 2 of the present application after 19 days of treatment. Figure 2 Figure 2A is a graph showing the H&E staining observation results of the back skin of mice in the control group. Figure 2 Figure 2B is a graph showing the H&E staining observation results of the back skin of mice in the DHT group. Figure 2 Figure 2C is a graph showing the H&E staining observation results of the back skin of mice in the DHT / luspatercept group. Figure 2 Figure 2D is a graph showing the statistical results of the number of hair follicles in each group. Figure 2 Figure 2E is a graph showing the statistical results of the dermal thickness in each group. DETAILED DESCRIPTION
[0023] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention or its application or use.
[0024] Unless otherwise specifically stated, the relative arrangement, numerical expressions, and values of the components and steps set forth in these embodiments do not limit the scope of the invention. It should also be understood that, for ease of description, the dimensions of the various parts shown in the drawings are not drawn to actual scale. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples shown and discussed herein, any specific values should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may include different values. It should be noted that similar reference numerals and letters in the following figures denote similar items; therefore, once an item is defined in one figure, it need not be further discussed in subsequent figures.
[0025] This invention provides the application of JAK inhibitors in products for the prevention and treatment of androgenetic alopecia. By exploring the application of ruxolitinib in alleviating hair loss in mice stimulated by DHT and the related molecular mechanisms, it clarifies the effectiveness of ruxolitinib in inhibiting abnormal hair follicle growth in mice induced by DHT, and proves the feasibility of ruxolitinib in promoting hair regeneration. This provides a basis for the intervention or treatment of androgenetic alopecia and demonstrates the feasibility of using ruxolitinib to intervene in and / or treat androgenetic alopecia by resisting the inhibition of hair follicle growth induced by DHT.
[0026] The present invention will be further described below with reference to the embodiments.
[0027] In this embodiment of the invention, the JAK inhibitor selected is ruxolitinib, whose CAS number is 941678-49-5.
[0028] The experimental animals used in this invention embodiment were 15 specific pathogen-free (SPF) grade adult male C57BL / 6J mice, 6 weeks old, weighing (25±2) g. The mice were provided by the Institute of Comparative Medicine, Yangzhou University.
[0029] In this embodiment of the invention, ruxolitinib phosphate cream (Opzelura) ®The following were purchased from Incyte Corporation, USA: Hematoxylin and eosin staining kit (Beijing Solarbio Science & Technology Co., Ltd.); Dihydrotestosterone (DHT) (Beijing Solarbio Science & Technology Co., Ltd.); Hair removal cream (Reckitt Benckiser Chemicals Ltd., France); Corn oil (Shanghai Yuanye Biotechnology Co., Ltd.); Canon EOS 7D MARK II digital camera (Canon Ltd.); Dermlite DL4 handheld dermatoscope (Dermlite Corporation, USA).
[0030] Example 1:
[0031] (1) Experimental preparation
[0032] Before the experiment began, the newly purchased male C57BL / 6 mice underwent a 7-day acclimatization period. Subsequently, these mice were randomly divided into 3 experimental groups of 5 mice each, following a randomization principle.
[0033] Solution preparation: DHT solution: Weigh 0.5 g DHT and dissolve it in 100 mL corn oil, sonicate, and store at 4℃ to prepare a DHT solution with a final concentration of 5 mg / mL.
[0034] The three experimental groups are as follows:
[0035] Control group: Hair was shaved, corn oil was injected intraperitoneally, and normal saline (NS) was injected subcutaneously.
[0036] DHT group: Hair was shaved and DHT solution was injected intraperitoneally to induce the AGA model.
[0037] DHT / Ruxolitinib group: Hair was shaved, DHT solution was injected intraperitoneally, and ruxolitinib phosphate cream was applied to the shaved area.
[0038] (2) Model establishment and drug administration
[0039] Day 0: Before the experiment began, all mice were shaved on the back and depilatory cream was applied to remove hair from a 3 cm × 4 cm area.
[0040] Day 1-Day 19: Starting from Day 1 of the experiment, for 19 consecutive days, mice in the DHT group and the DHT / ruxolitinib group were intraperitoneally injected with 250 μL of DHT solution daily; mice in the control group were intraperitoneally injected with 250 μL of corn oil daily. Simultaneously, the control group and the DHT group were subcutaneously injected with 300 μL of normal saline (NS) daily, while the DHT / ruxolitinib group had 200 mg of ruxolitinib phosphate cream applied to the shaved area daily.
[0041] Day 19: At the end of the experiment, skin samples were collected from the backs of all mice for biological indicator analysis in the following examples.
[0042] (3) Observation and Recording
[0043] Photography Recording: On days 0, 3, 7, 10, 13, 16, and 19 of the experiment, photographs were taken of the treated area on the backs of the mice to record hair growth. The results are as follows: Figure 1 As shown, the control group represents the control group, DHT represents the DHT group, and DHT / ruxolitinib represents the DHT / ruxolitinib group.
[0044] Figure 1 This study presents the dorsal hair growth in mice of the control, DHT, and DHT / ruxolitinib groups on days 0, 3, 7, 10, 13, 16, and 19 of the experiment. At day 13, the control and DHT / ruxolitinib groups showed significant hair regrowth, while the DHT group mice maintained pink skin on their backs with no hair growth. The DHT / ruxolitinib group showed significantly increased hair regrowth, with abundant hair growth on their backs, demonstrating a clear hair recovery effect. In contrast, the DHT group mice showed no hair regrowth until day 19, far less than the control and DHT / ruxolitinib groups in terms of hair coverage. These results indicate that ruxolitinib has a significant effect on resisting DHT-induced hair loss and promoting hair regrowth.
[0045] Example 2: Hematoxylin-eosin (H&E) staining of mouse skin tissue
[0046] Skin samples of 1 cm × 1 cm were taken from the back of mice, fixed with 4% paraformaldehyde, dehydrated, and embedded in paraffin. 5 μm thin sections were cut and baked in a 60℃ oven. The sections were treated in xylene for 15 min to remove paraffin, followed by a second soaking to ensure complete dewaxing. The sections were then stained in hematoxylin solution for 5 min, followed by rinsing with running water for 15 min. After staining, the sections were dehydrated stepwise in 75% and 90% ethanol for 10 min each. The sections were then immersed in 0.5% ethanol-eosin staining solution for 2 min and rinsed with running water for 1 min. After dehydration with anhydrous ethanol, the stained sections were cleared again in xylene for 3 min, and this process was repeated once. The sections were mounted with neutral resin and observed and photographed under a microscope.
[0047] The number of hair follicles was obtained by counting under a microscope; the thickness of the dermis was obtained by ImageJ software.
[0048] Figure 2The results of H&E staining of the dorsal skin of mice in each treatment group after 19 days are shown. Control represents the control group, DHT represents the DHT group, and DHT / Ruxolitinib represents the DHT / Ruxolitinib group.
[0049] The results showed that the dermal thickness of mice in the DHT group during the growth phase was less than that of mice in the control group and the DHT / ruxolitinib group, and the number of hair follicles in mice in the DHT group during the growth phase was less than that in mice in the control group and the DHT / ruxolitinib group. This indicates that ruxolitinib has a good effect on resisting the inhibition of hair follicle growth caused by DHT and has the effect of promoting hair regeneration.
[0050] Therefore, based on the above results, ruxolitinib has the effect of promoting hair regeneration and can effectively resist hair loss caused by DHT, demonstrating the potential value of ruxolitinib in the treatment of AGA and providing a new option for the treatment of AGA.
[0051] Unless otherwise specified, the raw materials and equipment used in this invention are all commonly used in the field; unless otherwise specified, the methods used in this invention are all conventional methods in the field.
[0052] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. Use of lucortinib in the manufacture of a product for preventing and / or treating androgenetic alopecia.
2. Use according to claim 1, characterized in that, The product includes a pharmaceutical product, a cosmetic product, a food product, or a food additive.
3. Use according to claim 2, characterized in that, The product is a pharmaceutical product, a cosmetic product, a food product, or a food additive for preventing and / or treating androgenetic alopecia by resisting dihydrotestosterone-induced hair follicle growth inhibition.
4. A preparation for treating androgenic alopecia, characterized by, The active ingredient of the product includes lucortinib.
5. The article of manufacture of claim 4, wherein, The active ingredient of the product is lucortinib.
6. The article of manufacture of claim 4, wherein, The product is a pharmaceutical product, a cosmetic product, a food product, or a food additive.
7. The article of manufacture of claim 6, wherein, The product is a pharmaceutical product, a cosmetic product, a food product, or a food additive for preventing and / or treating androgenetic alopecia by resisting dihydrotestosterone-induced hair follicle growth inhibition.
8. A preparation for treating androgenetic alopecia according to claim 6 or 7, characterized in that, The cosmetic product includes a hair care product and a skin external additive.