CN111714475A - Application of honokiol in preparation of medicine for treating and/or preventing rosacea - Google Patents
Application of honokiol in preparation of medicine for treating and/or preventing rosacea Download PDFInfo
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- CN111714475A CN111714475A CN202010832764.2A CN202010832764A CN111714475A CN 111714475 A CN111714475 A CN 111714475A CN 202010832764 A CN202010832764 A CN 202010832764A CN 111714475 A CN111714475 A CN 111714475A
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- rosacea
- honokiol
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- VVOAZFWZEDHOOU-UHFFFAOYSA-N honokiol Natural products OC1=CC=C(CC=C)C=C1C1=CC(CC=C)=CC=C1O VVOAZFWZEDHOOU-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 201000004700 rosacea Diseases 0.000 title claims abstract description 37
- FVYXIJYOAGAUQK-UHFFFAOYSA-N honokiol Chemical compound C1=C(CC=C)C(O)=CC=C1C1=CC(CC=C)=CC=C1O FVYXIJYOAGAUQK-UHFFFAOYSA-N 0.000 title claims abstract description 29
- BYTORXDZJWWIKR-UHFFFAOYSA-N Hinokiol Natural products CC(C)c1cc2CCC3C(C)(CO)C(O)CCC3(C)c2cc1O BYTORXDZJWWIKR-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 239000003814 drug Substances 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims description 12
- 241001303601 Rosacea Species 0.000 title abstract description 32
- 210000004969 inflammatory cell Anatomy 0.000 claims abstract description 25
- 206010015150 Erythema Diseases 0.000 claims abstract description 18
- 230000008595 infiltration Effects 0.000 claims abstract description 9
- 238000001764 infiltration Methods 0.000 claims abstract description 9
- 239000006071 cream Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 2
- 208000002874 Acne Vulgaris Diseases 0.000 claims 1
- 206010000496 acne Diseases 0.000 claims 1
- 231100000321 erythema Toxicity 0.000 abstract description 16
- 241000699670 Mus sp. Species 0.000 abstract description 13
- 206010067484 Adverse reaction Diseases 0.000 abstract description 9
- 230000006838 adverse reaction Effects 0.000 abstract description 9
- 210000000056 organ Anatomy 0.000 abstract description 7
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 6
- 210000004027 cell Anatomy 0.000 abstract description 6
- 206010040844 Skin exfoliation Diseases 0.000 abstract description 5
- 230000035618 desquamation Effects 0.000 abstract description 5
- 230000004580 weight loss Effects 0.000 abstract description 5
- 230000002159 abnormal effect Effects 0.000 abstract description 4
- 238000002474 experimental method Methods 0.000 abstract description 4
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 10
- 210000003491 skin Anatomy 0.000 description 8
- 206010030113 Oedema Diseases 0.000 description 6
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 238000010171 animal model Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 241000218378 Magnolia Species 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003777 experimental drug Substances 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 239000011159 matrix material Chemical group 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000174599 Enchophora rosacea Species 0.000 description 1
- IECPWNUMDGFDKC-UHFFFAOYSA-N Fusicsaeure Natural products C12C(O)CC3C(=C(CCC=C(C)C)C(O)=O)C(OC(C)=O)CC3(C)C1(C)CCC1C2(C)CCC(O)C1C IECPWNUMDGFDKC-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- 206010037867 Rash macular Diseases 0.000 description 1
- 206010037888 Rash pustular Diseases 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical compound O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 229960004675 fusidic acid Drugs 0.000 description 1
- 230000035874 hyperreactivity Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000029561 pustule Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Images
Classifications
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- 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
- A61P17/10—Anti-acne agents
Abstract
The invention provides an application of honokiol in preparing a medicine for treating and/or preventing rosacea. Experiments prove that the honokiol can obviously relieve the erythema condition of the mouse with the rosacea, reduce the infiltration of inflammatory cells, reduce the number of the inflammatory cells and effectively treat the rosacea. Meanwhile, after the mice with rosacea are administered with honokiol, adverse reactions such as desquamation, weight loss and the like can not be generated, and the morphology of each organ tissue cell is not abnormal. Therefore, the honokiol has good application prospect in preparing the medicine for treating and/or preventing the rosacea.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to an application of honokiol in preparation of a medicine for treating and/or preventing rosacea.
Background
Rosacea is a chronic disease characterized by inflammation and neurovascular hyperreactivity, with major involvement of the facial skin, and clinical features of rosacea including facial erythema, papules, and/or pustules, telangiectasia, and repeated flushing, which, although not a fatal disease, adversely affects the quality of life of patients with rosacea.
Clinical treatment methods for rosacea are mostly external medicines, such as tacrolimus ointment, fusidic acid cream, metronidazole gel and the like, but the medicines have poor treatment effects and are easy to relapse, and adverse reactions of local stimulation are generated in the using process, so that the skin is injured, and the life quality of patients is seriously affected. Therefore, how to treat rosacea safely and effectively remains a problem in the field of dermatology.
Therefore, the development of a new medicament which can effectively treat the acne rosacea and does not cause adverse reaction has very important significance.
Disclosure of Invention
The invention aims to provide application of honokiol in preparing a medicine for treating and/or preventing rosacea.
The invention provides an application of honokiol in preparing a medicine for treating and/or preventing rosacea.
Further, the medicament is an external preparation.
Further, the medicament is a liquid preparation for external use, a solid preparation, a cream or a cream.
Further, in the external liquid preparation, the concentration of honokiol is 5-10% mg/mL.
Further, the medicament is capable of improving skin erythema, reducing inflammatory cell infiltration, and/or reducing inflammatory cell numbers.
Further, the rosacea LL-37 induced rosacea.
Experimental results show that honokiol can remarkably relieve erythema of mice suffering from rosacea, reduce inflammatory cell infiltration, reduce the number of inflammatory cells and effectively treat the rosacea. Meanwhile, after the mice with rosacea are administered with honokiol, adverse reactions such as desquamation, weight loss and the like can not be generated, and the morphology of each organ tissue cell is not abnormal. The honokiol has good application prospect in preparing the medicine for treating and/or preventing the rosacea.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 is a photograph of the skin at the injection site of each group, wherein NHK group means and Magnolia phenol group means.
FIG. 2 is a picture of HE staining pathology of skin tissues of mice in each group, wherein NHK group represents and Magnolia phenol group.
Detailed Description
The raw materials and equipment used in the invention are known products and are obtained by purchasing commercial products.
EXAMPLE 1 treatment of LL-37 induced rosacea with honokiol
1. Experimental Material
1) Experimental drugs: dissolving honokiol with butanediol to obtain solution (mg/mL) with concentration of 0.5% and 1.0%; azelaic acid was dissolved in butanediol to a concentration of 15.0% (mg/mL).
2) Experimental animals: SPF-grade BALB/c female mice (6 weeks old) and special feed for the mice are purchased from Duoduoshu laboratory animals GmbH, and are fed in a laboratory for 1 week to adapt to the environment.
3) Main test reagents: hematoxylin stain and eosin stain were purchased from the zhhai Baso company; honokiol is purchased from shanghai sahn chemical technology limited; LL-37 was synthesized by Invivogen (San Diego, Calif.) under CAS number 597562-32-8; the substrate butanediol was purchased from Shanghai Demaol chemical Co.
2. Experimental methods
1) BALB/c mice were divided into 0.5% and magnolol group, 1.0% and magnolol group, 15.0% azelaic acid group, matrix group (i.e. butanediol group), LL-37 group (i.e. rosacea animal model group), and blank group (each group n ═ 9), and were pretreated: the experimental drugs were applied to the back skin (about 0.1 ml/cm) of each mouse of the corresponding group2) 2 times/day for 6 days; LL-37 and blank groups were not coated with any formulation.
2) Molding was performed on day 4: LL-37 (320. mu.M) was injected intradermally into the 0.5% and magnolol group, the 1.0% and magnolol group, the 15.0% azelaic acid group, the substrate group and the LL-37 group, and ultrapure water was injected intradermally into the blank group at an amount of 50. mu.l per 12 hours for 4 times.
3) Erythema scoring was performed 12 hours after the last LL-37/ultrapure injection (i.e. day 6 of drug application), then the mice were sacrificed and skin biopsies taken from the back injection site: a. observation of histopathological changes in mouse skin by HE staining and counting of inflammatory cells; b. in the experimental process, the general condition of the mice is observed, whether adverse reactions exist is noticed, and each organ tissue of the mice in the magnolol group and the blank group is taken to be prepared into pathological sections and HE staining, and the cell morphology of each organ is observed.
3. Results of the experiment
1) Erythema scoring results
The skin of the blank mouse has no erythema and edema; 0.5% and the magnolol group showed faint erythema with a blurred border, with mild edema; 1.0 percent of the extract and the magnolol group can be seen with erythema and no obvious edema; the 15.0% azelaic acid group showed faint erythema with a blurred border and no apparent edema; the stroma group showed clear-bordered, brightly colored erythema with edema; group LL-37 showed well-defined, darker red blotches with apparent edema (FIG. 1). From the erythema score results in Table 1, the erythema scores of the 1.0% and magnolol groups and the 15.0% azelaic acid group were statistically different (mean P <0.05), and the 1.0% and magnolol groups and the 15.0% azelaic acid group were not statistically different (mean P >0.05) compared to the substrate group and the LL-37 group, respectively. The honokiol is proved to be capable of remarkably reducing the erythema score of an LL-37-induced rosacea animal model, has remarkable treatment effect on the rosacea, and the treatment effect is increased along with the increase of the concentration of the honokiol.
TABLE 1 comparison of erythema scores and inflammatory cell counts at skin injection sites in mice
Note: n is 9.a: in contrast to group LL-37, p<0.05；b: in contrast to the matrix group, p<0.05；c: in contrast to the 15.0% azelaic acid group, p<0.05。
2) HE staining display and inflammatory cell counting results
HE staining showed: the blank group had an intact epidermal structure and no significant inflammatory cell infiltration in the dermal layer. 0.5 percent of magnolol group, 1.0 percent of magnolol group and 15.0 percent of azelaic acid group have complete epidermis structures, and a small amount of inflammatory cell infiltration can be seen in the dermis; local epidermal depletion in the stroma and LL-37 groups, vasodilation and more inflammatory cell infiltration in the dermis, dominated by lymphocytes and neutrophils (FIG. 2). Inflammatory cells were counted under x 400 fold light microscopy (results in table 1): inflammatory cell counts were significantly less in both the 0.5% and magnolol groups and the 15.0% azelaic acid group than in the LL-37 group (mean P <0.05), although there was no statistical difference compared to the stroma group (mean P > 0.05). Inflammatory cell counts were significantly less for both the 1.0% and magnolol groups than for the stroma and LL-37 groups (p < 0.05); also, the inflammatory cell counts were significantly less than 15.0% for the 1.0% and magnolol groups, with a statistical difference (p < 0.05). As can be seen, the 0.5% and magnolol groups had significantly lower numbers of inflammatory cells than the LL-37 group, with statistical differences (P < 0.05); the inflammatory cell number of the 1.0% honokiol group and the magnolol group is significantly less than that of the stroma group, the LL-37 group and the 15.0% azelaic acid group, and the statistical difference (P <0.05) is obtained, so that the honokiol can significantly reduce the inflammatory cell number of an LL-37 induced rosacea animal model, and has significant treatment effect on rosacea, and the treatment effect is increased along with the increase of the concentration of the honokiol.
3) Adverse reaction
The condition of each group of mice is good generally, and adverse reactions such as desquamation, weight loss and the like are not seen; HE staining neutralized morphology of tissue cells of various organs of the magnolol group.
The results show that the honokiol can obviously relieve the erythema condition of the mouse with the rosacea, reduce the infiltration of inflammatory cells, reduce the number of the inflammatory cells and effectively treat the rosacea. Meanwhile, after the mice with rosacea are administered with honokiol, adverse reactions such as desquamation, weight loss and the like can not be generated, and the morphology of each organ tissue cell is not abnormal.
In summary, the present invention provides the use of honokiol, magnolol, or a mixture thereof in the preparation of a medicament for the treatment and/or prevention of rosacea. Experiments prove that the honokiol can obviously relieve the erythema condition of the mouse with the rosacea, reduce the infiltration of inflammatory cells, reduce the number of the inflammatory cells and effectively treat the rosacea. Meanwhile, after the mice with rosacea are administered with honokiol, adverse reactions such as desquamation, weight loss and the like can not be generated, and the morphology of each organ tissue cell is not abnormal. Therefore, the honokiol has good application prospect in preparing the medicine for treating and/or preventing the rosacea.
Claims (6)
1. Use of honokiol in preparing medicine for treating and/or preventing acne vulgaris is provided.
2. Use according to claim 1, characterized in that: the medicine is an external preparation.
3. Use according to claim 2, characterized in that: the medicine is a liquid preparation, a solid preparation, a cream or a cream for external use.
4. Use according to claim 3, characterized in that: in the external liquid preparation, the concentration of honokiol is 5-10% mg/mL.
5. Use according to any one of claims 1 to 4, characterized in that: the medicament can improve skin erythema, reduce inflammatory cell infiltration, and/or reduce inflammatory cell numbers.
6. Use according to any one of claims 1 to 4, characterized in that: the acne rosacea is LL-37 induced acne rosacea.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911286238.4A CN110812345A (en) | 2019-12-13 | 2019-12-13 | Application of honokiol in preparation of medicine for treating and/or preventing rosacea |
| CN2019112862384 | 2019-12-13 |
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| CN111714475A true CN111714475A (en) | 2020-09-29 |
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| CN202010832764.2A Pending CN111714475A (en) | 2019-12-13 | 2020-08-18 | Application of honokiol in preparation of medicine for treating and/or preventing rosacea |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002076393A2 (en) * | 2001-03-23 | 2002-10-03 | Emory University | Antiagionecic, antitumor, chemopreventative agents |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002076393A2 (en) * | 2001-03-23 | 2002-10-03 | Emory University | Antiagionecic, antitumor, chemopreventative agents |
Non-Patent Citations (1)
| Title |
|---|
| 陈茵等主编: "《中药药理学》", 30 June 2012, 人民卫生出版社 * |
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Application publication date: 20200929 |