CN116514911A - Polypeptide and application thereof in preparation of medicines for treating chronic urticaria - Google Patents
Polypeptide and application thereof in preparation of medicines for treating chronic urticaria Download PDFInfo
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- CN116514911A CN116514911A CN202310422528.7A CN202310422528A CN116514911A CN 116514911 A CN116514911 A CN 116514911A CN 202310422528 A CN202310422528 A CN 202310422528A CN 116514911 A CN116514911 A CN 116514911A
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- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 30
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 30
- 229920001184 polypeptide Polymers 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 17
- 206010052568 Urticaria chronic Diseases 0.000 claims abstract description 15
- 208000024376 chronic urticaria Diseases 0.000 claims abstract description 15
- 210000002966 serum Anatomy 0.000 claims abstract description 15
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 2
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- 230000000694 effects Effects 0.000 abstract description 5
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- 238000011160 research Methods 0.000 abstract description 4
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- 102000003816 Interleukin-13 Human genes 0.000 description 7
- 108090000176 Interleukin-13 Proteins 0.000 description 7
- 102000004388 Interleukin-4 Human genes 0.000 description 7
- 108090000978 Interleukin-4 Proteins 0.000 description 7
- 229940028885 interleukin-4 Drugs 0.000 description 7
- 102000008070 Interferon-gamma Human genes 0.000 description 6
- 108010074328 Interferon-gamma Proteins 0.000 description 6
- 229960003130 interferon gamma Drugs 0.000 description 6
- 238000000034 method Methods 0.000 description 6
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- 238000002474 experimental method Methods 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
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- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
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- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
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- 238000002965 ELISA Methods 0.000 description 1
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- 230000006741 behavioral dysfunction Effects 0.000 description 1
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- 239000008338 calamine lotion Substances 0.000 description 1
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- 102000018358 immunoglobulin Human genes 0.000 description 1
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- 230000007794 irritation Effects 0.000 description 1
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- CPYIZQLXMGRKSW-UHFFFAOYSA-N zinc;iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+3].[Fe+3].[Zn+2] CPYIZQLXMGRKSW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a polypeptide and application thereof in preparing a medicament for treating chronic urticaria. The research of the invention discovers that the polypeptide has obvious curative effect on treating chronic urticaria, can regulate the immune dysfunction condition of the organism of a patient, and can improve the serum total IgE level and the inflammatory factor level of the organism of the patient.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to a polypeptide and application thereof in preparing a medicine for treating chronic urticaria.
Background
Related studies indicate that urticaria is caused by the combined action of various factors, which is one of the common diseases of clinical dermatology. The clinical manifestations of urticaria are mainly that the bodies of patients have dense wind clusters with different numbers and different sizes, and severe pruritus or vascular edema reaction are accompanied. Chronic urticaria is one of the clinical categories of urticaria, and the disease has the characteristics of frequency, repeatability and the like. Chronic urticaria diseases can occur at all ages, with a high risk of developing in women aged 40-50. Modern researches have found that the occurrence of chronic urticaria disease is closely related to pathogen infection, environmental factors, drug irritation, poor diet, vitamin D deficiency and the like.
The polypeptide is a compound formed by connecting amino acids, and has reports on related bioactive peptides such as plant protein, marine product protein, meat protein, milk protein, bean protein and the like, and the physiological functions of the polypeptide are mainly focused on antithrombotic, antihypertensive, antioxidant, bone-promoting, antitumor, immunity-regulating, anti-inflammatory, lipid-lowering, antibacterial, blood sugar-lowering and the like. However, the use of the polypeptide in the preparation of a medicament for treating chronic urticaria has not been reported at present.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides an application of polypeptide in preparing a medicament for treating chronic urticaria. In order to achieve the above purpose, the present invention provides the following technical solutions:
in a first aspect, the invention provides a polypeptide having the amino acid sequence ACDRAQHL.
In a second aspect, the invention provides the use of a polypeptide in the manufacture of a medicament for the treatment of chronic urticaria, wherein the amino acid sequence of the polypeptide is ACDRAQHL.
In a third aspect, the invention also provides the use of a polypeptide in modulating serum total IgE levels, wherein the amino acid sequence of the polypeptide is acraqhl.
In a fourth aspect, the invention also provides the use of a polypeptide in modulating the level of an inflammatory factor, wherein the amino acid sequence of the polypeptide is ACDRAQHL.
In a fifth aspect, the present invention also provides a medicament for treating chronic urticaria, the medicament comprising: a therapeutically effective dose of the polypeptide and pharmaceutically acceptable excipients.
The invention is different from the prior art in that the invention has the following technical effects:
the application of the polypeptide in preparing the medicament for treating the chronic urticaria is found through experiments, the prepared medicament has remarkable curative effect, can regulate the immune dysfunction condition of a patient, improve the serum total IgE level and the inflammatory factor level of the patient, and has lower occurrence risk of adverse reaction.
Drawings
FIG. 1 is a graph comparing symptom score levels in an observation group and an experimental group according to the present invention;
FIG. 2 is a graph comparing cell levels of T lymphocyte subsets in an observation group and an experimental group according to the present invention;
FIG. 3 is a graph comparing serum total IgE levels and inflammatory factor levels in the subject and experimental groups.
Detailed Description
The following examples facilitate a better understanding of the present invention, but are not intended to limit the same. The experimental methods in the following examples are conventional methods unless otherwise specified. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
1. Experimental materials
The polypeptide (ACDRAQHL) is synthesized by applicant by conventional solid phase synthesis method, and has molecular formula of C 37 H 61 N 11 O 10 S, molecular weight is 873.05Da, and molecular ion peak [ M+H ] is detected by mass spectrum] + Mass to charge ratio of 874Da and HPLC purity > 99%.
Deslorata citrate is ordered from Guangzhou sea Rui pharmaceutical Co., ltd.
2. Subjects and methods
1. Study object
92 chronic urticaria patients collected and treated in fourth-people hospitals in Changzhou are selected as study objects, basic data information such as gender, age, course of disease and education degree of the patients are collected, and the patients are divided into an observation group and an experimental group by adopting a random digital table method, wherein 46 patients are in each group. The study was approved by the ethics committee of the fourth people hospital in Changzhou, all patients and families informed of the study and signed the relevant consent.
2. Inclusion and exclusion criteria
The method comprises the following steps: 1) The patients are all diagnosed with chronic urticaria through clinical relevant detection; 2) The age of the patient is more than or equal to 18 years old; 3) The medical record data of the patient is complete; 4) The course of the disease of the patient is more than 6 weeks; 5) Urticaria occurs within 24 hours before the patient is admitted; 6) Patients have not received antihistaminic, anticholinergic, glucocorticoid etc. medications recently (14 d).
Exclusion: 1) Excluding those with severe organ function diseases; 2) Excluding allergic or related tabu reaction people in medicines, modes, instruments and the like used in the research institute; 3) Eliminating acute urticaria; 4) Excluding those suffering from malignant tumor diseases; 5) Eliminating the cases of serious malnutrition, anemia and the like; 6) Excluding those who are in a particular physiological phase; 7) Excluding those who combine mental disorders and cognitive, behavioral dysfunction disorders; 8) The study (patient and family) cannot be completely matched for various reasons.
3. Method of
After the patient is admitted, the calamine lotion is applied to the skin of the lesion; all patients were continuously treated for 1 month, and patients were instructed to take the diet (mainly light, spicy and pungent foods were prohibited) during the treatment.
Observation group: desloratadine citrate tablet (Guangzhou sea Rui pharmaceutical Co., yangzui pharmaceutical Co., ltd.) is administered orally at a dose of 8.8 mg/dose and a frequency of 1 dose/d.
Experimental group: the medicine prepared by the polypeptide and the conventional auxiliary materials is orally taken, the dosage is 5 mg/time, and the taking frequency is 1 time/d.
4. Observation index
Clinical effects: and (3) curing: the clinical symptoms of the patient completely disappear and last for at least one week; the effect is shown: the rash of the patient is basically cured, but wind cluster, itching and other conditions occur occasionally; the method is effective: the clinical symptoms of the patients are improved, but rash, wheal, itching and other conditions occur frequently; invalidation: the clinical symptoms of the patient were not significantly improved or even further worsened.
Symptom score level: before and after treatment, the relevant symptom score level of the patient is measured by using a nettle rash symptom score scale, wherein the scale comprises 4 items of wind cluster duration, wind cluster number, wind cluster size and pruritus, each score is 0-3 points, and the lower the score is, the lower the severity of the corresponding symptom of the patient is.
T lymphocyte subpopulation cell level: before and after treatment, 5mL of early morning fasting venous blood was collected from the patient, serum was routinely isolated, and the patient was examined for cd3+, cd4+/cd8+ ratio levels using a flow cytometer.
Serum total IgE levels and inflammatory factor levels: before and after treatment, 5mL of fasting venous blood of the patient in the early morning was collected, and serum immunoglobulin E (IgE) and interleukin-4 (IL-4), interleukin-13 (IL-13) and interferon-gamma (IFN-gamma) levels of the patient were detected by ELISA.
Adverse reaction conditions: adverse reaction conditions which are included in the observation of the research institute include: dry mouth, somnolence, dizziness, headache, weakness and gastrointestinal reactions.
4. Statistical method
The drawing software is GraphPad Prism 8; data were analyzed using SPSS 25.0; the measurement data is compared by using a t-test,a representation; count data is compared using x2 test, n (%). The comparison is statistically significant with P < 0.05.
3. Experimental results
1. Baseline data comparison
Of the 46 patients in the observation group, 21 men and 25 women; age 22-59 years, average age (38.68+ -5.84) years; the course of the disease is 6 weeks to 7 years, and the average course of the disease (3.11+/-1.16) years; educational level: 19 cases in senior high school and below, and 27 cases in college, university and above. Of the 46 patients in the experimental group, 20 men and 26 women; age 21-60 years, average age (38.75±5.79); the course of the disease is 6 weeks to 8 years, and the average course of the disease (3.19+/-1.21) years; educational level: high school and 17 cases below, college and 29 cases above. The baseline data for both groups of patients were comparable, with no significant differences in comparison (P > 0.05) as shown in Table 1.
Table 1 baseline data comparison
2. Comparison of clinical efficacy
The total effective rate of treatment in the observation group was 82.61%, the total effective rate of treatment in the experimental group was 97.83%, and the total effective rate of treatment in the experimental group was significantly higher than that in the observation group (P < 0.05) as shown in Table 2.
Table 2 comparison of clinical efficacy
3. Comparison of symptom score levels
As shown in fig. 1, the duration, size, number, and symptom score contrast (all, P > 0.05) of the wheal before treatment for both groups of patients; the duration, size, number, and symptom scores of the wind mass after treatment of the experimental group were significantly lower than those of the observed group (all, P < 0.05).
4. T lymphocyte subpopulation cell level comparison
As shown in fig. 2, the cd3+ before and after the treatment of the observation group were (55.32 ±5.87, 60.13±4.94), cd4+ was (29.54 ±3.26, 34.16±3.42), and cd4+/cd8+ was (0.97±0.45, 1.23±0.34), respectively; cd3+ before and after treatment of the experimental group were (55.43±5.92, 65.08±5.13), cd4+ was (29.76±3.41, 39.32 ±3.56), and cd4+/cd8+ was (0.98±0.42, 1.52±0.29), respectively. Cd3+, cd4+/cd8+ levels prior to treatment for both groups of patients were compared (all, P > 0.05); the CD3+, CD4+/CD8+ levels after treatment in the experimental group were significantly higher than those in the observed group (all, P < 0.05).
5. Comparison of serum Total IgE levels and inflammatory factor levels
As shown in FIG. 3, serum IgE before and after treatment of the observation group was (221.84 + -36.84, 105.26 + -20.54), IL-4 was (85.04 + -9.53, 53.58+ -6.02), IL-13 was (78.96 + -9.65, 41.86 + -7.25), IFN- γ was (9.58+ -1.86, 22.48+ -3.56), respectively; serum IgE before and after treatment of the experimental group were (221.68 + -36.79, 76.18+ -18.85), IL-4 was (84.98+ -9.46, 46.32 + -7.25), IL-13 was (78.72+ -9.38, 34.12+ -6.33), and IFN-gamma was (9.65+ -1.72, 34.19 + -4.38). Serum IgE levels before treatment and inflammatory factor levels such as IL-4, IL-13, IFN-gamma, etc. of the two groups of patients are compared (all, P > 0.05); serum IgE level and IL-4, IL-13, IFN-gamma and other inflammatory factors after treatment are obviously superior to those of the observation group (all, P < 0.05).
6. Adverse reaction condition comparison
The incidence of adverse reactions in the observation group was 10.87%, the incidence of adverse reactions in the experimental group was 13.04%, and the comparison of the incidence of adverse reactions (P > 0.05) between the two groups of patients is shown in Table 3.
TABLE 3 adverse reaction condition comparison
As can be seen from the above experiments, the CD3+, CD4+/CD8+ levels after treatment of the experimental group are significantly higher than those of the observed group (all, P < 0.05); serum IgE levels after treatment of experimental groups and levels of inflammatory factors such as IL-4, IL-13, IFN-gamma and the like are significantly better than those of the observation groups (all, P < 0.05), and the results show that compared with the treatment scheme of desloratadine citrate, the polypeptide can further regulate the immune dysfunction condition of a patient body and improve the serum total IgE and inflammatory factor levels of the patient body. The incidence of adverse reaction of the observation group is 10.87%, the incidence of adverse reaction of the experiment group is 13.04%, and the incidence of adverse reaction of two groups of patients is compared (P is more than 0.05), which indicates that the polypeptide of the invention can improve the treatment effect of the patients, improve the immune dysfunction and inflammatory reaction condition of the organisms of the patients, and simultaneously not exacerbate the occurrence risk of the adverse reaction condition of the patients.
The above examples are only illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solution of the present invention should fall within the scope of protection defined by the claims of the present invention without departing from the spirit of the present invention.
Claims (5)
1. A polypeptide, characterized in that: the amino acid sequence is ACDRAQHL.
2. Use of a polypeptide in the manufacture of a medicament for the treatment of chronic urticaria, wherein the amino acid sequence of the polypeptide is acraqhl.
3. Use of a polypeptide for modulating serum total IgE levels, wherein the amino acid sequence of the polypeptide is ACDRAQHL.
4. Use of a polypeptide for modulating the level of an inflammatory factor, wherein the amino acid sequence of the polypeptide is ACDRAQHL.
5. The use according to any one of claims 2-4, wherein the medicament comprises: a therapeutically effective dose of the polypeptide and pharmaceutically acceptable excipients.
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| CN117946286A (en) * | 2024-03-17 | 2024-04-30 | 永创恒新生物医学科技(北京)有限公司 | Polypeptide TDI-18 and application thereof |
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| CN117510592A (en) * | 2023-11-11 | 2024-02-06 | 永创恒新生物医学科技(北京)有限公司 | Bioactive peptide and application thereof in preparing skin wound repair cosmetics |
| CN117510592B (en) * | 2023-11-11 | 2024-05-31 | 杭州达维先医药科技有限公司 | Bioactive peptide and application thereof in preparing skin wound repair cosmetics |
| CN117946286A (en) * | 2024-03-17 | 2024-04-30 | 永创恒新生物医学科技(北京)有限公司 | Polypeptide TDI-18 and application thereof |
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