CN111249441A - Application of small molecular oligopeptide in preparation of medicine for treating psoriasis - Google Patents
Application of small molecular oligopeptide in preparation of medicine for treating psoriasis Download PDFInfo
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- CN111249441A CN111249441A CN202010276929.2A CN202010276929A CN111249441A CN 111249441 A CN111249441 A CN 111249441A CN 202010276929 A CN202010276929 A CN 202010276929A CN 111249441 A CN111249441 A CN 111249441A
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- small molecular
- medicine
- skin
- oligopeptide
- psoriasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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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
- A61P17/06—Antipsoriatics
Abstract
The invention discloses an application of small molecular oligopeptide in preparing a medicine for treating psoriasis, wherein the amino acid sequence of the small molecular oligopeptide is as follows: AHWSGHCCL, the small molecular oligopeptide can obviously relieve the skin expression of psoriasis only by external smearing administration; moreover, the micromolecule medicine is easy to degrade and metabolize after being absorbed, and the inflammation inhibition mechanism of the micromolecule medicine is different from the existing hormone cream, so that the side effect is very small; third, topical administration has significant local effects and little systemic effects.
Description
Technical Field
The invention relates to the technical field of research and development and preparation of psoriasis medicines, and particularly relates to application of small molecular oligopeptides in preparation of medicines for treating psoriasis.
Background
Psoriasis is an immune-mediated chronic, recurrent, inflammatory, systemic disease, typically clinically manifested as squamous erythema or plaque, localized or widespread, non-contagious, difficult to treat, often suffering from lifelong.
The pathogenesis of psoriasis involves various factors such as heredity, immunity and environment, and keratinocyte hyperproliferation or joint synoviocytes and chondrocyte inflammation is caused by immune reaction mainly mediated by T lymphocytes and jointly participated by various immune cells.
Since the specific pathogenesis of psoriasis is still unclear, there is no effective treatment method at present, and the systemic and local side effects of the treatment using hormones are great for patients, while simple antiallergic drugs can relieve symptoms, but have limited effects because they cannot solve the fundamental problems.
Disclosure of Invention
In research, the invention discovers that the small molecular oligopeptide has a very good effect on treating psoriasis, has small side effect and is relatively thorough in treatment.
In view of this, the present invention proposes the following technical solutions:
the application of a small molecular oligopeptide in preparing a medicine for treating psoriasis is disclosed, wherein the amino acid sequence of the small molecular oligopeptide is as follows: AHWSGHCCL (SEQ ID NO.1)
Preferably, in the above application, the medicament is in a form of external administration.
Preferably, in the above application, the dosage form is an ointment.
Preferably, in the above application, the composition further comprises an auxiliary material.
Preferably, in the above application, the auxiliary materials include an excipient and a pH regulator.
Compared with the prior art, the invention has the following beneficial effects:
the invention discovers that the micromolecule oligopeptide with simple chemical structure can obviously relieve the skin expression of psoriasis only by external smearing administration; the micromolecule oligopeptide medicine is easy to degrade and metabolize after being absorbed, and the inflammation inhibition mechanism of the micromolecule oligopeptide medicine is different from that of the existing hormone cream, so that the side effect is very small; third, topical administration has significant local effects and little systemic effects.
Drawings
Fig. 1 shows the dorsal skin changes (first row), pathological section HE staining (second row) and body weight changes (left one in the third row), total lesion score (middle in the third row) and epidermal thickness (right one in the third row) of the three groups of mice of example 1 after different treatments.
FIG. 2 is the change in immunoglobulin light chain kappa in the skin (first row), the transcriptome expression levels of skin S100a8, S100a9, K16, CXCL1 and TNF α (second row), and the protein expression levels of IL-17A and IFN-. gamma.in the serum (third row) of the three groups of mice after different treatments in example 1.
FIG. 3 is the changes in γ δ T cells and neutrophils in the skin (second and third left rows, respectively), IL-17A in draining lymph nodes (first left row), and changes in spleen size morphology (top right) and its spleen index (bottom right) after different treatments in three groups of mice of example 1.
Detailed Description
The technical solutions of the present invention will be described in detail and fully with reference to the accompanying examples, so that those skilled in the art can understand and better practice the technical solutions.
Example 1
The F991 cream was purchased as follows: water, vaseline, sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, and F991 (7.5% by mass).
In the cream, the vaseline mainly plays a role in shaping and prolonging the action time of the effective medicinal components; sodium chloride, disodium hydrogen phosphate and sodium dihydrogen phosphate are used for maintaining the ion concentration and pH value of effective medicinal components; f991 is a medicinal component, and is a micromolecular oligopeptide with the amino acid sequence as follows: AHWSGHCCL (SEQ ID NO.1), which inhibits the inflammatory response by inhibiting the deposition of immunoglobulin free light chains; water is used as the solvent.
Animal experiments: a psoriasis mouse model was prepared using Imiquimod Cream (IMQ) to simulate the appearance of skin in psoriasis patients.
The experimental animals were divided into several groups:
A. healthy control group (vasoline): 62.5mg of vaseline is smeared on the skin of a hair-fading area on the back of a mouse 2 times a day, and the interval between the first administration and the second administration is 6 hours;
B. molding control group (IMQ): applying 62.5mg of IMQ to the skin of the hair-losing area on the back of the mouse once a day; after 6 hours, 62.5mg of vaseline is coated on the same position, and the vaseline is coated once a day;
C. modeling treatment group (F991): applying 62.5mg of IMQ to the skin of the hair-losing area on the back of the mouse once a day; f991, 62.5 mg/piece is smeared on the same position after 6 hours, and the smearing is carried out once a day;
the groups were fed water normally and the skin appearance of the mice was observed daily for an experimental period of 7 days.
The experimental results are as follows:
1. f991 is able to alleviate psoriasis-like skin lesions caused by IMQ.
Referring to fig. 1, panel Vaseline in the first row is the back skin of the healthy control mice, which shows that the skin of the healthy control mice is fine and uniform without erythema, dandruff and thickening; FIG. IMQ is the back skin of a model-made mouse treated with a control drug, showing that the skin of the group is scattered and distributed with erythema, dandruff and thickening of the epidermis; FIG. F991 shows that the skin erythema of the group is significantly reduced, with little or no dandruff, and no significant thickening of the epidermis, on the back skin of a model mouse with psoriasis-like lesions treated with the F991 cream; both the total skin damage score (middle third row) and the weight change (left one in third row) suggest that F991 treatment results in a decrease in skin damage and a decrease in weight with a more rapid recovery. The second row is a representative pathological section (HE staining) of the dorsal skin of each group of mice, which shows a reduction in epidermal thinning, dermal infiltration of inflammatory cells and vascular proliferation after F991 treatment; the epidermal thickness was measured and counted microscopically at a plurality of points within 3 fields of view for 4, 1 and 3 sections, 1 section (third row, right one), and morphological analysis showed a significant decrease in epidermal thickening after treatment with F991.
2. F991 reduces IMQ causing upregulation of skin lesion-associated genes and inflammatory factor expression.
Referring to FIG. 2, after the mice were sacrificed on day 4, proteins and RNA were extracted from the dorsal skin of the mice, and the expression of Igk in the skin was examined (immunohistochemistry: first row left one, second left three, immunoblot: first row right one up and down), the expression of S100a8, S100a9 and K16 associated with skin lesions and CXCL1 and TNF associated with inflammation were examined in the transcriptome, and IL-17A and INF γ were examined in the serum (third row), and after F991 treatment, the levels of transcripts of S100a8, S100a9, K16, CXCL1 and TNF α were significantly reduced in skin lesions, and both IL-17A and INF γ were reduced in the model treatment group (F991) compared to the model control group (IMQ).
3. F991 reduced infiltrating neutrophils in the skin.
Referring to fig. 3, the spleen of the molding control group (IMQ) was significantly increased compared to the healthy control group (Vaseline), and the spleen of the molding treatment group (F991) was not significantly different from that of the molding control group (IMQ) (upper right), but the spleen index indicating the systemic immune response was higher in the molding control group (IMQ) (lower right) because the body weight of the molding control group (IMQ) was decreased more than that of the molding treatment group (F991). IL-17A (left first row), gamma delta T and neutrophils in the skin of the neck lymph nodes are detected by flow, and the modeling treatment group (F991) is reduced compared with the modeling control group (IMQ).
The experimental result shows that the F991 has better treatment effect on psoriasis.
The inventive concept is explained in detail herein using specific examples, which are given only to aid in understanding the core concepts of the invention. It should be understood that any obvious modifications, equivalents and other improvements made by those skilled in the art without departing from the spirit of the present invention are included in the scope of the present invention.
Sequence listing
<110> Beijing university
Application of small molecular oligopeptide in preparation of medicine for treating psoriasis
<130>P20200031
<141>2020-04-10
<160>1
<170>SIPOSequenceListing 1.0
<210>1
<211>9
<212>PRT
<213> Artificial sequence (Artificial sequence)
<400>1
Ala His Trp Ser Gly His Cys Cys Leu
1 5
Claims (5)
1. The application of the small molecular oligopeptide in preparing the medicine for treating psoriasis is characterized in that the amino acid sequence of the small molecular oligopeptide is as follows: AHWSGHCCL are provided.
2. The use of claim 1, wherein the medicament is in a form for topical administration.
3. The use of claim 2, wherein the dosage form is a paste.
4. The use of claim 2, wherein the composition further comprises an adjuvant.
5. The use of claim 1, wherein the excipient comprises an excipient, a pH adjuster.
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1342779A1 (en) * | 2002-03-06 | 2003-09-10 | Fornix Biosciences N.V. | Means and methods for manipulating hypersensitivity-like responses |
US20050049183A1 (en) * | 1998-07-09 | 2005-03-03 | Redegeld Franciscus Antonius M. | Inhibition of protein binding to mast cells |
CN105597079A (en) * | 2016-01-11 | 2016-05-25 | 中国人民解放军第三军医大学第一附属医院 | Medicine for treating psoriasis |
-
2020
- 2020-04-10 CN CN202010276929.2A patent/CN111249441A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050049183A1 (en) * | 1998-07-09 | 2005-03-03 | Redegeld Franciscus Antonius M. | Inhibition of protein binding to mast cells |
EP1342779A1 (en) * | 2002-03-06 | 2003-09-10 | Fornix Biosciences N.V. | Means and methods for manipulating hypersensitivity-like responses |
CN105597079A (en) * | 2016-01-11 | 2016-05-25 | 中国人民解放军第三军医大学第一附属医院 | Medicine for treating psoriasis |
Non-Patent Citations (2)
Title |
---|
ZHI-QIANG HUANG等: "Localization of a single binding site for immunoglobulin light chains on human Tamm-Horsfall glycoprotein", 《THE JOURNAL OF CLINICAL INVESTIGATION》 * |
焦素敏等: "非布司他在慢性肾功能衰竭合并高尿酸血症老年患者中的有效性及安全性观察", 《广东医学》 * |
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