CN112494488B - Application of rebamipide in preventing alopecia and growing hair - Google Patents
Application of rebamipide in preventing alopecia and growing hair Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- 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
Abstract
The invention provides application of rebamipide and physiologically acceptable salts or solvates thereof in preparing a skin application composition and application of the skin application composition in pharmaceutical preparations, cosmetics, nursing products and cosmetics. The composition for skin application and the further applied preparation can comprehensively and effectively aim at various reasons of alopecia, so that the composition is more helpful for balancing the metabolic condition of a demand object and adjusting the mental state of the demand object to achieve better treatment and nursing synergistic effect, and the rebamipide has high safety and small toxic and side effects, thereby having wide application prospects in the fields of pharmaceutical preparations, cosmetics, nursing products, cosmetics and the like.
Description
Technical Field
The invention belongs to the field of compounds and preparations thereof, and particularly relates to application of rebamipide in preparing anti-hair loss and hair growth preparations, and further application in the fields of medicines, cosmetics, nursing products, cosmetics and the like.
Background
Alopecia refers to the phenomenon of hair loss. The normal metabolism of the human beings is also accompanied by the shedding and the regeneration of hair in the process of carrying out the metabolism in the new city, and belongs to the normal metabolism phenomenon of organisms. The normal hair loss is the hair in the catagen and telogen phases, and the normal amount of hair can be maintained because the hair entering the catagen phase and the hair newly entering the anagen phase are constantly in dynamic balance. However, pathological hair loss is caused by abnormal hair loss due to various causes, such as excessive stress, staying up overnight, or endocrine disorders. Alopecia often affects the mental appearance of people, and the incidence rate of alopecia symptoms also rises along with the fact that social competition is intensified in recent years. The development industry of drugs and auxiliary cosmetics for treating alopecia is well-trained, but clinical medicines or effective products are still relatively poor at present, and the FDA only certifies two therapies (minoxidil and finasteride) for treating alopecia. The reason for this is that modern medicine is not completely clear about its etiology and pathogenesis, and thus there is no clinically effective treatment.
Alopecia can be classified into psychogenic alopecia, seborrheic alopecia (androgenetic alopecia), chemical alopecia, physical alopecia, nutritional alopecia, and endocrine alopecia. Seborrheic alopecia, psychogenic alopecia and chemical alopecia caused by chemotherapy are the most common of the alopecia.
Psychogenic alopecia is mainly due to severe emotional changes, mental abnormalities and alopecia. Mainly comprises the problems of insomnia, irritability, anxiety, low mood, high excitement and the like. The emotion of a person can influence the body by the behavior awareness of the person. Functionally, emotions can regulate endocrine, make the body prone to metabolism, such as vigorous metabolism, slow metabolism and the like, give people self-perception of being energetic or weak, and thus affect hair growth. Thus, actives that promote the natural growth of hair tend to have a potentially synergistic effect in regulating mental status.
Seborrheic Alopecia is also called Androgenic Alopecia (AGA), and is mainly caused by seborrheic physical, endocrine is vigorous, and epidermal metabolism is abnormal to cause Alopecia. Seborrheic alopecia is usually more common in male, young and strong, and as the age increases, endocrine metabolism slows down, and alopecia can be gradually relieved. This is the principle that some people take hormone inhibitors to reduce hair loss by slowing metabolism. At present, the best-approved minoxidil tincture is mainly used for treating androgenetic alopecia, is a potassium ion channel opener, has the effect of expanding peripheral blood vessels, and can shorten the resting period of hair follicles and enable the hair follicles to enter the growth period in advance. However, according to the data provided by the FDA, even minoxidil is only 39% effective at the vertex of the head.
Chemotherapy Alopecia (CIA) is one of the side effects caused by the use of a large number of cytotoxic drugs with indiscriminate killing during the course of treatment of malignant tumors. Compared with physiological pain, the method has the advantages that the image of a patient is damaged, the privacy of the patient is deprived, great negative effects are generated on self-esteem of the patient, and even anxiety, depression and willingness of the patient are caused. Even a subset of patients may choose a less effective treatment or therefore reject treatment because of the difficulty in addressing alopecia, and it is still practical and necessary to address the problem of chemotherapy alopecia.
Rebamipide (Rebamipide), the chemical name of which is 2- (4-chloroformamido) -3- [2(lH) -quinolone-4-yl ] propionic acid, is a drug for treating gastric ulcer, can prevent gastric ulcer and accelerate ulcer healing, and has the effects of increasing blood flow of gastric mucosa, synthesis of prostaglandin E2 and gastric mucus secretion, promoting healing of peptic ulcer and improving inflammation through a plurality of researches. However, no literature has been published to report the relevant application of rebamipide in the aspects of alopecia and hair growth. The structural formula is as follows:
in conclusion, there is a need to find an active substance that can promote the natural growth of hair, reduce hair loss, be safe and stable without irritation, and fully satisfy the requirements for nursing, treating and beautifying effects for various reasons caused by hair loss.
Disclosure of Invention
In order to solve the problems of the prior art, the present invention provides the use of rebamipide and physiologically acceptable salts or solvates thereof for the preparation of a composition for dermal application.
According to an embodiment of the invention, the skin application composition is a composition having a synergistic effect of one or more of an antiandrogen, a hair growth stimulating, an anti-sebum effect; in some embodiments, the skin application composition is an antiandrogen composition; in some embodiments, the skin application composition is a composition for stimulating hair growth; in some embodiments, the skin application composition is an anti-sebum composition.
According to an embodiment of the invention, the skin comprises tissue covering the surface of the human or animal body, further comprising tissue covering the surface of the face or body, as well as the scalp and hair; the hair encompasses body hair and head hair (e.g., few hairs, "hairs" in alopecia further encompass body hair and head hair); preferably, the skin is the scalp; preferably the hair is hair.
According to an embodiment of the invention, the subject to which the skin-applied composition is applied includes humans and animals.
According to an embodiment of the present invention, said stimulating hair growth comprises stimulating the production of new hair, as well as promoting the growth of existing hair in a healthy state (reducing the risk of hair loss).
According to embodiments of the present invention, the skin-applied composition can inhibit androgens, stimulate the proliferation of hair follicle papilla cells and hair growth of hair follicle cells, while controlling sebum hypersecretion.
According to an embodiment of the present invention, the anti-sebum composition may be applied to condition or improve skin problems caused by excessive secretion of sebaceous glands, such as follicular dilatation, acne, seborrheic dermatitis, and the like.
According to an embodiment of the invention, the dermally administrable composition is used for the prevention and/or treatment of hair loss in a patient after chemotherapy.
According to an embodiment of the invention, the dermally administrable composition is for use in the prevention and/or treatment of androgenic alopecia.
According to an embodiment of the invention, the dermally administrable composition is used for preventing and/or treating alopecia resulting from autoimmune disease alopecia areata.
According to an embodiment of the present invention, in some embodiments, the composition comprises rebamipide and a physiologically acceptable salt or solvate thereof as the only physiologically active ingredient; in other embodiments, the composition comprises, in addition to rebamipide and physiologically acceptable salts or solvates thereof as an active ingredient, other physiologically active ingredients.
The invention further provides the application of the skin application composition in pharmaceutical preparations, cosmetics, nursing products and cosmetics.
According to an embodiment of the invention, the pharmaceutical preparation is applied for preventing, caring and treating oligotrichia and alopecia, promoting hair health and growth, and inhibiting sebum secretion.
The pharmaceutical preparation can be applied topically through skin, and the dosage form of the preparation is selected from cream, patch, ointment, cream preparation, gel, spray, etc., and can also be orally taken (i.e. oral preparation), and the oral preparation comprises tablet, granule, capsule, oral liquid, pill, suspension, dripping pill, etc. The pharmaceutical formulation further comprises a physiologically acceptable carrier (e.g. a material with biocompatibility), for example optionally comprising surfactants, excipients, humectants, emulsification promoters, suspending agents, salts or buffers for regulating the osmotic pressure, colorants, fragrances, stabilizers, bactericides, preservatives or other conventional supplements. According to an embodiment of the present invention, the pharmaceutical formulation may include rebamipide and physiologically acceptable salts or solvates thereof in an amount of 0.01 wt% to 20 wt% based on the total weight of the formulation. Preferably, the rebamipide and the physiologically acceptable salt or solvate thereof account for 3 to 7 weight percent of the total weight of the preparation.
According to an embodiment of the present invention, the cosmetic, care or beauty product may be selected from a hair shampoo, a hair conditioner, a hair care, a hair conditioner essence, a hair oil, a hair conditioner, a hair lotion, a scalp hair tonic, a hair essence, a scalp cream, a hair conditioner, a hair spray, a hair pack, a eyebrow care, and the like.
Advantageous effects
The inventor finds that rebamipide can promote the growth speed of naturally growing hair, increase the hair length and the hair weight, care hair follicles, condition or improve the excessive secretion of sebaceous glands, particularly can prevent and treat alopecia caused by chemotherapeutic drugs, effectively treat androgen alopecia and alopecia areata, and can more effectively increase the growth weight, the length and the like of newly added hair or residual hair after alopecia compared with a marketed drug minoxidil. The physiological activity of rebamipide can comprehensively and effectively aim at various reasons of alopecia, so that the rebamipide is more beneficial to balancing the metabolic condition of a demand object and adjusting the mental state of the demand object to achieve better treatment and nursing synergistic effect, and the active ingredients have high safety and small toxic and side effects, so that the rebamipide has wide application prospect in the fields of medical nursing and the like.
Drawings
FIG. 1 is a histogram of hair length of rebamipide on mice of a natural hair growth model;
FIG. 2 is a histogram of the hair weight of rebamipide on mice of the natural hair growth model;
fig. 3 is a bar graph of hair growth scores of rebamipide on mice model for alopecia after chemotherapy;
fig. 4 is a histogram of hair length of rebamipide on mice model for alopecia after chemotherapy;
fig. 5 is a histogram of hair weight of rebamipide on mice model for alopecia after chemotherapy;
fig. 6 is a line graph of the hair growth score of rebamipide on AGA model mice;
FIG. 7 is a histogram of hair length of rebamipide on an AGA model mouse;
fig. 8 is a histogram of the gross weight of rebamipide on AGA model mice.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to specific embodiments. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
In the examples, "%" is used as a mass percentage unless otherwise specified.
Example 1: curative effect evaluation experiment of rebamipide on C57BL/6 mouse natural hair growth model
1. Laboratory animal
The experimental animals are male C57BL/J6, 8 weeks old and 18-20g in weight, and are purchased from the comparative medical center of Yangzhou university. The C57BL/6 mouse is bred under normal conditions, the temperature is 25 +/-2 ℃, the humidity is 50% -70%, the illumination and the darkness are carried out alternately for 12h respectively, the mouse can eat and drink water freely, the corn cob padding is replaced every two days, and the experiment is started after the mouse adapts to the breeding environment for 7 days.
2. Drug configuration
4% chloral hydrate: 0.4g chloral hydrate is dissolved in 10ml of normal saline, and is subjected to vortex centrifugation to be completely dissolved to prepare 4% chloral hydrate solution.
2.14% (O/W) rebamipide cream for external use, which is prepared from the following raw material medicaments:
400 parts of rebamipide, 1000 parts of stearic acid, 200 parts of glyceryl stearate, 200 parts of beeswax, 200 parts of palm oil, 600 parts of butanediol, 200 parts of ethanol, 4800 parts of water, 3 parts of carbomer and 2 parts of triethanolamine. The external cream of the invention is prepared according to the raw material components:
(1) weighing stearic acid, glyceryl stearate, beeswax and palm oil according to a certain proportion, heating in a water bath to be molten, filtering, and preserving at a constant temperature of 70-80 ℃;
(2) weighing butanediol, ethanol, water, carbomer and triethanolamine according to a certain proportion, adding into the solution, heating in water bath, stirring, and emulsifying for 10-20 min;
(3) adding the weighed rebamipide raw material, stirring while adding until the solution is condensed into cream to obtain 4% (O/W) rebamipide external cream;
2.2 oral formulation of rebamipide: the dosage is 100mg/kg, the drug is dissolved by 0.5 percent CMC-Na before use, the solution is centrifuged by vortex, and the mice are orally administrated with gastric lavage after being completely suspended.
3. Natural alopecia model establishment
After the mice are weighed, 4% chloral hydrate is intraperitoneally injected according to the dose of 10 mul/g, after the mice are anesthetized, all back hairs of the mice are carefully shaved by an electric shaver, wounds are avoided, depilatory wax paper with the size of 5.25 multiplied by 2.5cm is cut, palms are warm for 1min and torn, the electric shaver is attached to the center of the backs of the mice along the growth direction of the hairs of the mice, the palms are continuously warmed for 1min, the tails of the mice are fixed, the wax paper is quickly torn in the direction opposite to the growth direction of the hairs, then the electric shaver is wiped by using the emollient paper, all the hairs in the terminal phase are pulled out, the development of the hair follicles in the highly synchronous growth phase is induced, and the hair follicles are not different from the growth phase of the spontaneously formed hair follicles in shape.
24C 57BL/6 mice were randomly assigned to a model control group (model), minoxidil tincture group (Mino), rebamipide ointment group (Reba ointment), rebamipide oral group (Reba oral), 6 mice per group. The administration was performed 1 time per day for 13 days in the depilated area of the back of the mouse from day 2 after the depilation. The concentration of commercially available minoxidil tincture was 5%, and the solution was diluted to 2.5% by adding an equal volume of anhydrous ethanol, and the dose was 200. mu.l per one. Control group was given a blank cream without drug; the rebamipide group was administered at a concentration of 2.5% and about 0.2g of a cotton swab was applied to the depilatory area per administration.
4. Curative effect evaluation experiment of rebamipide on hair natural growth of unhaired mouse
On the 14 th day after administration, the mice were injected with 10ml/kg of 4% chloral hydrate intraperitoneally, when the mice were anesthetized stably, the mice were carefully nipped with forceps to take 10 fixed-site hairs on the back of the mice, about 10 hairs were taken with each nipper, the hairs were placed on clean white paper, the length was measured with a vernier caliper, the longest value was selected as the recorded value, and the whole measurement process was repeated 2 times.
As a result, as shown in fig. 1, the rebamipide ointment group significantly increased hair length compared to the blank cream control group, which had a statistical significance (× P < 0.01), and significantly promoted hair growth. Rebamipide oral group also increased hair length (P-0.1103). Compared with the positive drug minoxidil, the rebamipide ointment group was able to increase hair length, but had no statistical significance (P ═ 0.143).
After the hair length measurement is finished, the hair in the molding area is carefully shaved off by using an animal shaver, the hair is weighed by using a one-hundred-ten-thousand balance after being collected and stored by using weighing paper, and the hair weight value is recorded.
The results are shown in fig. 2, and compared with the blank cream control group, the rebamipide ointment group significantly increased hair weight, and had statistical significance (× P < 0.01), indicating that rebamipide can promote hair growth. Compared with the positive drug minoxidil, the rebamipide ointment group also increased hair weight (P ═ 0.0064). Rebamipide oral group also increased hair weight (. about.p < 0.01).
It can be seen that rebamipide has significant efficacy in promoting the natural hair growth of mice, and particularly, the ointment preparation is even better than the positive drug minoxidil in terms of hair weight.
Example 2: efficacy evaluation experiment of rebamipide on C57BL/6 mouse chemotherapy alopecia model
1. Laboratory animal
The experimental animals are male C57BL/J6, 8 weeks old and 18-20g in weight, and are purchased from the comparative medical center of Yangzhou university. The C57BL/6 mouse is bred under normal conditions, the temperature is 25 +/-2 ℃, the humidity is 50% -70%, the illumination and the darkness are carried out alternately for 12h respectively, the mouse can eat and drink water freely, the corn cob padding is replaced every two days, and the experiment is started after the mouse adapts to the breeding environment for 7 days.
2. Drug configuration
The 4% chloral hydrate was prepared as above.
The rebamipide ointment is prepared as above.
Rebamipide oral suspension formulation was as above.
Cyclophosphamide for injection: 0.2g cyclophosphamide is dissolved in 20ml physiological saline, and the solution is prepared into 10mg/ml solution after being completely dissolved by vortex centrifugation.
3. Establishment of chemotherapy alopecia model
After the mice are weighed, 4% chloral hydrate is intraperitoneally injected according to the dose of 10 mul/g, after the mice are anesthetized, all back hairs of the mice are carefully shaved by an electric shaver, wounds are avoided, depilatory wax paper with the size of 5.25 multiplied by 2.5cm is cut, palms are warm for 1min and torn, the electric shaver is attached to the center of the backs of the mice along the growth direction of the hairs of the mice, the palms are continuously warmed for 1min, the tails of the mice are fixed, the wax paper is quickly torn in the direction opposite to the growth direction of the hairs, then the electric shaver is wiped by using the emollient paper, all the hairs in the terminal phase are pulled out, the development of the hair follicles in the highly synchronous growth phase is induced, and the hair follicles are not different from the growth phase of the spontaneously formed hair follicles in shape.
On the 9 th day after depilation, the hair follicles in the depilation region entered the early stage of growth phase VI, and cyclophosphamide solution with the concentration of 80mg/kg and 10mg/ml was intraperitoneally injected in a single dose to induce the growth inhibition of the hair follicles in all the growth phases and thus the hair loss after chemotherapy.
4. Therapeutic experiment on depilated mice
24 depilated mice were randomized into 4 groups of 6 mice: control group, rebamipide ointment group, rebamipide oral group, minoxidil group. Control group was given a blank cream without drug; the concentration of the rebamipide group is 2.5%, and about 0.2g of cotton swab dipping paste is used for applying to a depilation area in each administration; the concentration of commercially available minoxidil tincture was 5%, and the solution was diluted to 2.5% by adding an equal volume of anhydrous ethanol, and the dose was 200. mu.l per one. The administration was continued 1 time per day from day 2 after depilation for a total of 13 days to day 5 after cyclophosphamide molding.
5. Curative effect evaluation experiment of rebamipide on hair chemotherapy alopecia of depilated mice
And 6 days after the cyclophosphamide is modeled, injecting 10ml/kg of 4% chloral hydrate into the abdominal cavity of the mouse, photographing under standard conditions to record the back skin condition and the hair growth condition of each group of mice and scoring and counting when the mouse is anesthetized and stabilized. Grading standard: the remaining hair area is a proportion of the total area of the epilation area.
The results are shown in fig. 3, and compared with the blank cream control group, the rebamipide ointment group has significantly improved hair growth score and statistical significance (. P < 0.05). Rebamipide ointment increased hair growth score compared to the positive drug minoxidil, but had no statistical significance (P ═ 0.259). The rebamipide oral group was similar to the minoxidil score with no significant difference (P0.804), but it was improved compared to the model group (P0.0157). Rebamipide can apparently inhibit alopecia caused by chemotherapeutic drugs, and the ointment has better effect than an oral preparation.
Carefully forceps the hair at 10 fixed positions on the back of the mouse by using forceps, taking about 10 hairs by using forceps each time, placing the hairs on clean white paper, measuring the length by using a vernier caliper, taking the longest value as a recorded value, and repeating the whole measuring process for 2 times.
The results are shown in fig. 4, where the rebamipide ointment group significantly increased hair length compared to the blank cream control group, with statistical significance (× P < 0.01). Compared to the positive drug minoxidil, the rebamipide ointment group was able to increase hair length, but had no statistical significance (P-0.0907). Rebamipide oral group also significantly increased hair length (0.0036) slightly more than minoxidil, but without significant difference. Rebamipide can inhibit alopecia caused by chemotherapy drugs.
After the hair length measurement is finished, the hair in the molding area is carefully shaved off by using an animal shaver, the hair is weighed by using a one-hundred-ten-thousand balance after being collected and stored by using weighing paper, and the hair weight value is recorded.
The results are shown in fig. 5, where the rebamipide ointment group significantly increased the remaining hair weight compared to the blank cream control group, with statistical significance (. P < 0.05). Compared with the positive drug minoxidil, the rebamipide ointment group was able to increase the remaining hair weight, but had no statistical significance (P ═ 0.168). Rebamipide oral control group also increased hair weight (P ═ 0.022) compared to the model group. Rebamipide can inhibit alopecia caused by chemotherapy drugs.
Example 3: rebamipide curative effect evaluation experiment on C57BL/6 mouse androgen alopecia model
1. Laboratory animal
The experimental animals are C57BL/J6, 8 weeks old and 18-20g in weight, and are purchased from the comparative medical center of Yangzhou university. The C57BL/6 mouse is bred under normal conditions, the temperature is 25 +/-2 ℃, the humidity is 50% -70%, the illumination and the darkness are carried out alternately for 12h respectively, the mouse can eat and drink water freely, the corn cob padding is replaced every two days, and the experiment is started after the mouse adapts to the breeding environment for 7 days.
2. Drug configuration
The 4% chloral hydrate was prepared as above.
The rebamipide ointment is prepared as above.
Rebamipide oral suspension formulation was as above.
Testosterone propionate injection (1 mL: 25mg, Guangzhou Baiyunshanming pharmaceutical Co., Ltd.) was diluted to 1mg/mL with edible oil before use. And (3) diluting the testosterone propionate diluent, and oscillating the diluted testosterone propionate diluent for 2 minutes by using a vortex mixer to fully and uniformly mix the diluted testosterone propionate diluent and the testosterone propionate diluent for later use.
Modeling of AGA mice
Injection of testosterone propionate was performed subcutaneously in the back of the mice parallel to the spinal area at a dose of 5mg/kg d. After dilution to 1mg/mL, 100mL was injected subcutaneously per mouse once a day for 28 days.
C57BL/J6 mouse androgen alopecia animal model modeling success judgment standard: 1 the back hair is exfoliated and partially fused into large pieces. 2 significant seborrhea was visible on the back. Pathological manifestations of the tissue, a smaller proportion of terminal hair/vellus hair, atrophy, degeneration and disappearance of hair follicles. The above 3 pieces are met at the same time, and the model can be considered to be successful.
Treatment experiment of AGA depilated mice
24 depilated mice were randomized into 4 groups of 6 mice: control group, rebamipide ointment group, rebamipide oral group, minoxidil group. Control group was given a blank cream without drug; the concentration of the rebamipide group is 2.5%, and about 0.2g of cotton swab dipping paste is used for applying to a depilation area in each administration; the concentration of commercially available minoxidil tincture was 5%, and the solution was diluted to 2.5% by adding an equal volume of anhydrous ethanol, and the dose was 200. mu.l per one. The treatment was performed simultaneously with the AGA molding, and the same administration was performed for 28 days.
Mice were scored by photographing after they were anesthetized with isoflurane every week from the start of molding.
5. Curative effect evaluation experiment of rebamipide on AGA alopecia of unhairing mice
Photographs of hair growth were scored weekly, as described above. Grading standard: the remaining hair area is a proportion of the total area of the epilation area.
The results are shown in fig. 6, where the rebamipide ointment group had significantly improved hair growth scores compared to the blank cream control group. Rebamipide ointment also increased the hair growth score compared to the positive drug minoxidil. Similarly, the oral group of rebamipide also performed better than minoxidil, but there was no significant difference. Rebamipide apparently inhibits androgenic alopecia.
Carefully forceps the hair at 10 fixed positions on the back of the mouse by using forceps, taking about 10 hairs by using forceps each time, placing the hairs on clean white paper, measuring the length by using a vernier caliper, taking the longest value as a recorded value, and repeating the whole measuring process for 2 times.
The results are shown in fig. 7, where the rebamipide ointment group significantly increased hair length compared to the blank cream control group, with statistical significance (. about.p < 0.01). Rebamipide ointment increases hair length compared to the positive drug minoxidil, but has no statistical significance (P. 0.3597). Rebamipide oral group also significantly increased mouse hair length (═ P ═ 0.0101). In conclusion, rebamipide can inhibit androgenic alopecia.
After the hair length measurement is finished, the hair in the molding area is carefully shaved off by using an animal shaver, the hair is weighed by using a one-hundred-ten-thousand balance after being collected and stored by using weighing paper, and the hair weight value is recorded.
The results are shown in fig. 8, and the rebamipide ointment group significantly increased the remaining hair weight compared to the blank cream control group, with statistical significance (× P < 0.01). Compared to the positive drug minoxidil, the rebamipide ointment group was able to increase the remaining hair weight, but had no statistical significance (P-0.1243). The rebamipide oral group can also significantly increase the weight of the mouse hair (0.0089), and the effect is similar to that of minoxidil. Rebamipide inhibits androgenic alopecia and maintains the maximum hair weight.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (13)
1. Use of rebamipide and physiologically acceptable salts thereof for the preparation of a skin application composition, characterized in that said skin application composition is a composition for stimulating hair growth.
2. Use according to claim 1, wherein the skin comprises tissue covering a surface of a human or animal body.
3. Use according to claim 2, characterized in that the skin comprises the scalp.
4. Use according to claim 1 or 2, wherein said stimulating hair growth comprises stimulating the production of new hair, and promoting the growth of existing hair in a healthy state.
5. Use according to claim 1 or 2, characterized in that the dermally administrable composition is used for the prevention and/or treatment of hair loss after chemotherapy in a patient; can be used for preventing and/or treating androgenic alopecia.
6. Use according to claim 1 or 2, the dermally administrable composition being applied in pharmaceutical preparations, cosmetics.
7. Use according to claim 6, wherein the dermally administrable composition is applied to a pharmaceutical preparation; the pharmaceutical preparation is applied to preventing, nursing and treating oligotrichia and alopecia and promoting hair health and growth.
8. Use according to claim 7, wherein the pharmaceutical formulation is administered topically through the skin, and the formulation is in a form selected from the group consisting of a cream, a patch, an ointment, a cream formulation, a gel and a spray.
9. Use according to claim 7, wherein the pharmaceutical formulation further comprises a physiologically acceptable carrier.
10. Use according to claim 7, characterized in that the rebamipide and the physiologically acceptable salts thereof represent from 3% to 7% by weight of the total weight of the formulation.
11. Use according to claim 6, characterized in that the cosmetic is selected from shampoos, conditioners, hair rinses, hair oils, hair lotions, scalp creams, hair gels, hair sprays, hair films, eyebrow lotions.
12. Use of rebamipide and physiologically acceptable salts thereof for the preparation of an oral formulation for stimulating hair growth.
13. Use according to claim 12, wherein the oral formulation is selected from tablets, granules, capsules, oral liquid formulations, pills, dripping pills.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011184429A (en) * | 2010-02-10 | 2011-09-22 | Univ Of Tsukuba | Composition containing low-molecular antioxidant and high-molecular formed, cyclic nitroxide radical compound |
| CN103554210A (en) * | 2012-01-05 | 2014-02-05 | 中国药科大学 | Sterides 5 alpha-reductase inhibitor, as well as preparation method and medical application thereof |
| CN109381466A (en) * | 2017-08-02 | 2019-02-26 | 中国药科大学 | Promote the therapeutic agent of diabetic wound healing |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011521896A (en) * | 2008-04-15 | 2011-07-28 | サーコード コーポレイション | Topical LFA-1 antagonists for use in local treatment for immune related disorders |
| US20110052678A1 (en) * | 2010-11-05 | 2011-03-03 | Shantha Totada R | Method for treating age related macular degeneration |
-
2020
- 2020-06-17 CN CN202010554850.1A patent/CN112494488B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011184429A (en) * | 2010-02-10 | 2011-09-22 | Univ Of Tsukuba | Composition containing low-molecular antioxidant and high-molecular formed, cyclic nitroxide radical compound |
| CN103554210A (en) * | 2012-01-05 | 2014-02-05 | 中国药科大学 | Sterides 5 alpha-reductase inhibitor, as well as preparation method and medical application thereof |
| CN109381466A (en) * | 2017-08-02 | 2019-02-26 | 中国药科大学 | Promote the therapeutic agent of diabetic wound healing |
Non-Patent Citations (4)
| Title |
|---|
| HUMAN SCALP HAIR FOLLICLES EXPRESS PROSTAGLANDIN E2 LIPID MEDIATOR AND RECEPTORS FOR PGE2;Karzan Ghafur Khidhir et al.;《Journal of University of Zakho》;20131231;第1卷(第2期);第541页 * |
| Karzan Ghafur Khidhir et al..HUMAN SCALP HAIR FOLLICLES EXPRESS PROSTAGLANDIN E2 LIPID MEDIATOR AND RECEPTORS FOR PGE2.《Journal of University of Zakho》.2013,第1卷(第2期),第533-542页. * |
| Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2;Sherin Zakaria et al.;《J Immunotoxicol》;20160731;第13卷(第4期);摘要 * |
| Sherin Zakaria et al..Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2.《J Immunotoxicol》.2016,第13卷(第4期),第453-462页. * |
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