CN114028372B - Application of glutamine as active ingredient in preparation of psoriasis treatment medicine, psoriasis treatment medicine and preparation method thereof - Google Patents

Application of glutamine as active ingredient in preparation of psoriasis treatment medicine, psoriasis treatment medicine and preparation method thereof Download PDF

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CN114028372B
CN114028372B CN202111302286.5A CN202111302286A CN114028372B CN 114028372 B CN114028372 B CN 114028372B CN 202111302286 A CN202111302286 A CN 202111302286A CN 114028372 B CN114028372 B CN 114028372B
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glutamine
psoriasis
preparation
use according
sodium
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CN114028372A (en
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彭聪
陈翔
陈超
张德阗
朱武
李捷
匡叶红
周星辰
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Xiangya Hospital of Central South University
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Xiangya Hospital of Central South University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • YGENERAL 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
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to application of glutamine as an active ingredient in preparation of a psoriasis treatment medicine, the psoriasis treatment medicine and a preparation method thereof. Through long-term study, researchers of the invention firstly find and prove that glutamine has obvious therapeutic effect on psoriasis according to the scale area and severity index (PASI) score and scale HE staining of psoriasis, and can effectively relieve the increase of MDSCS cell population, th1 and Th17 cell population and the decrease of Tregs cell population. The invention provides a new application of glutamine and a new medicine for treating psoriasis. Researches show that the glutamine has obvious efficacy for treating psoriasis no matter applied to external medicines or internal medicines, has wide application prospect and has larger popularization and application value. In addition, since glutamine is the most abundant amino acid in human body, the glutamine has small side effect on human body, and reduces research and development cost and manufacturing cost.

Description

Application of glutamine as active ingredient in preparation of psoriasis treatment medicine, psoriasis treatment medicine and preparation method thereof
Technical Field
The invention relates to the technical field of psoriasis treatment, in particular to application of glutamine as an active ingredient in preparation of a psoriasis treatment medicine, the psoriasis treatment medicine and a preparation method thereof.
Background
Psoriasis is a common chronic, recurrent and inflammatory skin disease, and clinically mainly shows erythema and scales, has specificity in histopathology, and shows excessive proliferation of epidermal keratinocytes, excessive keratinization with keratinization insufficiency, hypertrophic acanthosis, sparse inflammatory cell infiltration around blood vessels of the dermis superficial layer and the like. Psoriasis has a morbidity of 0.1% -3% in natural population, and has a complex pathogenesis and is easy to repeatedly attack.
Most psoriasis is a mild and moderate patient, and external drug treatment is a main treatment method and occupies an indispensable position. 80% of patients with psoriasis vulgaris are mild, so topical treatment is the preferred treatment regimen for psoriasis vulgaris. The psoriasis external medicine commonly used at present comprises glucocorticoid, tretinoin, vitamin D derivative, dithranol, tar preparation, calcineurin inhibitor and the like. Dithranol, tar formulations and glucocorticoids are limited in use due to the large side effects, whereas tretinoin, calcineurin inhibitors and vitamin D derivatives are not very desirable. The effect of the compound preparation of calcipotriol betamethasone ointment of the glucocorticoid and the vitamin D derivative which are recently marketed is slightly better than that of calcipotriol, but the cost is high. The limited topical drug options and the susceptibility to tolerance have been the bottleneck in the topical treatment of psoriasis.
In addition, methotrexate, cyclosporine, tretinoin, azathioprine, leflunomide, mycophenolate mofetil, glucocorticoids, antibiotics and biologicals are common drugs for the treatment of patients with severe psoriasis in systemic administration. Although these drugs have a curative effect on the condition of the patient, their effect on other systems of the patient, such as liver and kidney, is particularly important in daily diagnosis and treatment. Meanwhile, the application range of the medicines is affected by the bone marrow suppression effect of methotrexate, azathioprine and mycophenolate mofetil, adverse reaction of the nervous system of cyclosporine and hormone excess caused by long-term use of glucocorticoid. Biological agents, although fast in efficacy, are expensive and limited in terms of use, also limit their value in psoriasis treatment.
Therefore, the search for a new medicine with good curative effect and small side effect has important significance for treating psoriasis.
Disclosure of Invention
Based on the above, it is necessary to provide a new medicament for treating psoriasis with good therapeutic effect and little side effect.
In one aspect of the present invention, there is provided the use of glutamine as an active ingredient in the manufacture of a medicament for the treatment of psoriasis.
In another aspect, the present invention provides a psoriasis therapeutic agent, the active ingredient of which consists essentially of glutamine.
In one embodiment, the psoriasis treating medicament is in the form of a solution, lotion, liniment, ointment, plaster, paste or patch.
In one embodiment, the psoriasis therapeutic agent is in the form of a solution consisting essentially of glutamine and a solvent.
In one embodiment, the solvent is normal saline.
In one embodiment, the concentration of glutamine in the psoriasis therapeutic agent is from 0.02g/mL to 2g/mL.
In one embodiment, the concentration of glutamine in the psoriasis therapeutic agent is 0.04g/mL.
In one embodiment, the psoriasis therapeutic agent further comprises one or more of diluents, preservatives, buffers, disintegrants, antioxidants, suspending agents, colorants and excipients.
In one embodiment, the diluent is selected from one or more of propylene glycol, vegetable oil and mineral oil, the preservative is selected from one or more of sorbic acid, methyl sorbate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, benzyl parahydroxybenzoate, sodium methyl parahydroxybenzoate, benzoic acid and benzyl alcohol, and the buffer is selected from one or more of sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium citrate, sodium tartrate and sodium acetate.
In another aspect, the present invention provides a method for preparing a psoriasis therapeutic agent, comprising the steps of: mixing glutamine with a solvent to obtain the psoriasis therapeutic drug.
Glutamine (2-amino-5-carboxyvaleramide) is the most abundant amino acid in humans and plays a vital role in cell division. In addition, it has been found that the metabolic processes not only provide carbon in the metabolism of cells, but also provide nitrogen as a major source of nitrogen-containing compounds in the body. Therefore, glutamine has a critical role in cell energy production and biosynthesis, and has no substantial side effects on the human body. Currently there are studies showing that glutamine metabolism may be a target for tumor therapy and may play a more important role in regenerative medicine. The role of glutamine in the treatment of disease is being developed from different perspectives, but the use of glutamine as an active ingredient in the treatment of psoriasis has not been reported.
Through long-term study, researchers of the invention firstly find and prove that glutamine has obvious therapeutic effect on psoriasis according to the scale area and severity index (PASI) score and scale HE staining of psoriasis, and can effectively relieve the increase of MDSCS cell population, th1 and Th17 cell population and the decrease of Tregs cell population. The invention provides a new application of glutamine and a new medicine for treating psoriasis. Researches show that the glutamine has obvious efficacy for treating psoriasis no matter applied to external medicines or internal medicines, has wide application prospect and has larger popularization and application value. In addition, since glutamine is the most abundant amino acid in human body, the glutamine has small side effect on human body, and reduces research and development cost and manufacturing cost.
Drawings
FIG. 1 is a photograph of the ears of the first, second, third and fourth groups of mice on day 6 in animal experiment one;
FIG. 2 is a graph of PASI scores from day one to day six for ear lesions in a first, second, third, and fourth group of mice in animal experiment one;
FIG. 3 is a HE staining of the ear lesions of the first, second, third and fourth groups of mice in animal experiment one on day six;
FIG. 4 is a plot of skin thickness statistics for the sixth day of ear skin lesions in the first, second, third and fourth groups of mice in animal experiment one;
FIG. 5 is a graph of flow results of ear skin cells of a first, second, third, and fourth group of mice in animal experiment one, wherein A is the detection result of mononuclear MDSCs cell population, B is the detection result of Th1 cell population, and C is the detection result of Tregs cell population;
FIG. 6 is a photograph of the back of the first, second and third groups of mice on day 6 in animal experiment two;
FIG. 7 is a graph of PASI scores from day one to day six for the back skin lesions of the first, second and third groups of mice in animal experiment two;
FIG. 8 is a HE staining of the back skin lesions of the first, second and third groups of mice in animal experiment two for the sixth day;
FIG. 9 is a plot of skin thickness statistics for the sixth day of back skin lesions in the first, second and third groups of mice in animal experiment two;
fig. 10 is a graph of the back skin cell flow results of the first, second and third groups of mice in animal experiment two, wherein a is the detection result of mononuclear MDSCs cell population and B is the detection result of Th17 cell population.
Detailed Description
The present invention will be described more fully hereinafter in order to facilitate an understanding of the present invention, and preferred embodiments of the present invention are set forth. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
Terminology
PASI score (Psoriasis Area and Severity Index) is a score for the severity of skin lesions (including erythema, infiltration, scaling) and area of skin lesions in patients with integrated psoriasis. The final score calculated by a specific formula is often used to evaluate the severity of psoriasis vulgaris and is a scoring standard that is internationally used for the degree of psoriasis lesions.
MDSCs are short for english abbreviation for Myeloid-derived suppressor cells (Myeloid-derived suppressor cells), which are derived from Myeloid progenitor cells and immature Myeloid cells (immature Myeloid cells, IMCs). Under normal conditions, dendritic Cells (DC), macrophages and precursors of granulocytes can be rapidly differentiated into mature granulocytes, DCs and macrophages, and enter corresponding organs and tissues to exert normal immune functions, and the IMCs account for about 0.5% of peripheral blood mononuclear cells. Under other pathological conditions such as tumors, infections, inflammations, sepsis, surgical injuries, and the like, the precursor cells from these myeloid lineages are prevented from maturation under the action of cytokines, and thus stay in various differentiation stages to become MDSCs with immunosuppressive functions. They are recruited, migrated, and amplified by cytokines, which increase their number and proportion in the peripheral blood by about 10-fold, about 10% of the Peripheral Blood Mononuclear Cells (PBMCs) of patients, throughout the entire process of disease development.
Tregs are Regulatory T cells (Regulatory cells), a subset of T cells that control autoimmune reactivity in vivo, and were also known as Suppressor T cells in the early days. Regulatory T cells can be classified into naturally occurring natural regulatory T cells (n T-regs) and induced adaptive regulatory T cells (a T-regs or iT-regs), such as Th3 and Tr1, and CD8 Treg and NKT cells, etc., and are closely related to autoimmune diseases, and abnormal expression thereof may lead to autoimmune diseases. Wherein Tr1 cells secrete IL-10 and Th3 cells secrete TGF-beta.
Th1, type 1 helper T cells, are predominantly immune responses against intracellular bacteria and protozoa, are predominantly interleukin 12 (IL-12) driven to elicit, and the cytokine of major execution is gamma interferon (IFN-gamma). Th17, type 17 helper T cell, is mainly immune response against extracellular bacteria and mold, and is mainly driven and induced by interleukin 6 (IL-6) and TGF-beta, and its main cytokines are interleukin 1 (IL-1) interleukin 6 (IL-6) and TNF-alpha.
HE staining is one of staining methods commonly used in hematoxylin-eosin staining (HE staining), abbreviated as HE staining, and paraffin section techniques. Hematoxylin dye solution is alkaline, and mainly causes chromatin in nuclei and nucleic acid in cytoplasm to be purple blue; eosin is an acid dye that primarily reds the cytoplasmic and extracellular matrix components. HE staining is the most basic and widely used technical method in histology, embryology, pathology teaching and scientific research.
In one aspect, the present invention provides the use of glutamine as an active ingredient in the manufacture of a medicament for the treatment of psoriasis.
Glutamine is an amide of glutamic acid, L-glutamine is an amino acid encoded in protein synthesis, a mammalian nonessential amino acid, which can be converted from glucose in vivo, is a white crystalline or crystalline powder, is soluble in water, is insoluble in methanol, ethanol, ether, benzene, acetone, chloroform and ethyl acetate, is odorless, and is slightly sweet. Unstable in neutral solution, can be easily decomposed into glutamine or propyl esterified into pyrrolecarboxyl alcohol in alcohol, alkali or hot water, has no odor, and has slight sweet taste. Glutamine is the most abundant free amino acid in muscle, accounting for about 60% of the total free amino acid in human body, and has a fasting plasma glutamine concentration of 500-750 mu mol/L, and has the following structural formula:
in addition, glutamine metabolic processes have been found to not only provide carbon in cellular metabolism, but also provide nitrogen as a major source of nitrogen-containing compounds in the body. Therefore, glutamine has a critical role in cell energy production and biosynthesis, and has no substantial side effects on the human body. Currently there are studies showing that glutamine metabolism may be a target for tumor therapy and may play a more important role in regenerative medicine. The role of glutamine in the treatment of disease is being developed from different perspectives, but the use of glutamine as an active ingredient in the treatment of psoriasis has not been reported.
Through long-term study, researchers of the invention firstly find and prove that glutamine has obvious therapeutic effect on psoriasis according to the scale area and severity index (PASI) score and scale HE staining of psoriasis, and can effectively relieve the increase of MDSCS cell population, th1 and Th17 cell population and the decrease of Tregs cell population. The invention provides a new application of glutamine and a new medicine for treating psoriasis. Researches show that the glutamine has obvious efficacy for treating psoriasis no matter applied to external medicines or internal medicines, has wide application prospect and has larger popularization and application value. In addition, since glutamine is the most abundant amino acid in human body, the glutamine has small side effect on human body, and reduces research and development cost and manufacturing cost.
The active ingredient of the psoriasis therapeutic drug of an embodiment of the invention mainly comprises glutamine.
In a specific example, the psoriasis treating drug is in the form of a solution, lotion, liniment, ointment, plaster, paste or patch. It will be appreciated that the psoriasis treatment drug may be an external drug or an internal drug, and the administration mode may be subcutaneous injection, intravenous injection, oral administration, application, etc.
In a specific example, the psoriasis therapeutic agent is in the form of a solution consisting essentially of glutamine and a solvent.
In a specific example, the solvent is physiological saline, but is not limited thereto.
In a specific example, the concentration of glutamine in the psoriasis therapeutic agent is from 0.02g/mL to 2g/mL. Alternatively, the concentration of glutamine in the psoriasis therapeutic agent is 0.04g/mL. It will be appreciated that the specific concentration may be adjusted as desired depending on the condition or individual situation.
In a specific example, the psoriasis therapeutic drug further comprises one or more of diluents, preservatives, buffers, disintegrants, antioxidants, suspending agents, colorants and excipients.
In a specific example, the diluent is selected from one or more of polyethylene glycol, propylene glycol, vegetable oil, and mineral oil. In a specific example, the preservative is selected from one or more of sorbic acid, methyl sorbate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, benzyl parahydroxybenzoate, sodium methyl parahydroxybenzoate, benzoic acid, and benzyl alcohol. In a specific example, the buffer is selected from one or more of sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium citrate, sodium tartrate, and sodium acetate. In a specific example, the disintegrant is selected from one or more of croscarmellose sodium, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, or low substituted hydroxypropyl cellulose. In a specific example, the antioxidant is selected from one or more of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetic acid, dibutylhydroxytoluene, glycine, inositol, ascorbic acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid, and sodium metabisulfite. In a specific example, the suspending agent is selected from one or more of beeswax, ethyl hydroxyethyl cellulose, chitin, chitosan, methyl cellulose, carboxymethyl cellulose, agar, hydroxypropyl methyl cellulose and xanthan gum. In one specific example, the colorant is selected from one or more of carbon black, iron brown, iron red, and titanium dioxide. In a specific example, the excipient is selected from one or more of mannitol, glucose, lactose, dextran, and sodium chloride.
In a specific example, the psoriasis treating drug is a topical ointment, for example, a cream or ointment.
In a specific example, the psoriasis therapeutic agent is mainly prepared from a matrix and glutamine as an active ingredient.
In a specific example, the psoriasis treating drug is an ointment. Further, in the above psoriasis treatment drug, the matrix comprises lanolin, white petrolatum and/or DMSO (dimethyl sulfoxide). The topical unguent is in the form of ointment, and can be directly applied on the skin surface of patient.
In a specific example, the psoriasis treating drug is a cream. Further, in the above psoriasis therapeutic agent, the base comprises stearyl alcohol, white vaseline, glyceryl monostearate, sodium dodecyl sulfate, glycerol, ethyl parahydroxybenzoate and water.
The preparation method of the psoriasis treating medicine provided by the embodiment of the invention comprises the following steps: mixing glutamine with solvent or matrix to obtain the psoriasis therapeutic agent. It will be appreciated that the method of preparation may be adapted as desired, depending on the dosage form or formulation.
The following are specific examples.
Example 1
The preparation method of the external preparation comprises the following steps: 400mg of glutamine is dissolved in 10mL of physiological saline to prepare a 4% glutamine physiological saline preparation for treating psoriasis, and the preparation is bottled for standby.
Comparative example 1
The preparation method of the external preparation comprises the following steps: 400mg of alanine was dissolved in 10mL of physiological saline to prepare a 4% alanine physiological saline preparation as a control of the 4% glutamine physiological saline preparation, which was bottled for use.
Comparative example 2
The preparation method of the external preparation comprises the following steps: only 10mL of physiological saline was used as a control for the 4% glutamine physiological saline formulation.
Example 2
Preparation of an oral preparation: 4g of glutamine is dissolved in 100mL of physiological saline to prepare a 4% glutamine physiological saline oral preparation for treating psoriasis, and the oral preparation is bottled for standby.
Comparative example 3
Preparation of an oral preparation: 100mL of physiological saline is used as a control of the 4% glutamine physiological saline oral preparation.
The following are animal tests.
Imiquimod (IMQ) is an agonist of Toll-like receptor (Tolllike receptor, TLR) 7/8, mainly for topical treatment of vulvar and perianal warts and actinic keratosis. It has been found that external application of imiquimod to mouse skin induces psoriasis-like lesions and histological changes in mouse skin, which have many similarities to human psoriasis pathology. The imiquimod-induced mouse model can well simulate psoriasis symptoms similar to those of a human body in aspects of skin thickening, keratinocyte related protein abnormality, inflammatory cell infiltration, related inflammatory cytokines and the like. The model is simple and easy to operate, and is stable, so that the model is one of psoriasis models with the widest research and application.
Animal experiment one
20 SPF-grade (no specific pathogen-grade experimental animals) BALB/C mice were randomly divided into 4 groups of 5 mice each. The first group is a control group, and does not perform any treatment; the second group is IMQ+Vehicle group, and 20 μl of physiological saline of comparative example 2 is added dropwise before and after half an hour of ear-coating imiquimod; the third group is IMQ+4% alanine group, and 20 μl of 4% alanine physiological saline preparation of comparative example 1 is added dropwise before and after half an hour before ear-coating imiquimod; the fourth group was imq+4% glutamine group, and 20 μl of the 4% glutamine physiological saline formulation of example 1 was added dropwise to the ear half an hour before and after imiquimod application.
After each group is continuously coated for 6 days, the ear skin lesions of each group of mice are scored and examined for psoriasis-like symptoms of the mice by the area and severity index (PASI), then the mice are killed by weighing and photographing, the ear skin lesions are taken for HE staining experiments to examine the thickness of the epidermis, namely the proliferation condition of keratinocytes and the quantity change of cells flowing type psoriasis-related immune cells, and meanwhile, the spleen of the mice is taken for weighing and photographing.
The PASI scoring principle is as follows: the severity of skin inflammation was assessed daily, including skin thickness, crusting, erythema. Scoring is carried out by adopting a 5-point system (0-4):
skin thickness: 0: the skin is smooth and has no wrinkles; 1: slight folds of skin appear at the edges of the applied area; 2: slight folds appear on the skin in the area of application; 3: the wrinkling degree of the coating area is further deepened; 4: on the basis of the score of 3, the mice have the conditions of weight reduction, poor state and the like;
scabbing: 0: the skin is smooth and has no scales; 1: slight scaling of the skin occurred in the applied area; 2: the skin of the application area is entirely covered by scales; 3: the scale degree of the coating area is further deepened; 4: on the basis of the score of 3, the mice have the conditions of weight reduction, poor state and the like;
erythema: 0: skin is smooth; 1: the skin of the applied area appeared slightly red; 2: the skin of the applied area turns red entirely; 3: the red color of the coated area is further deepened; 4: on the basis of the score of 3, the mice have the conditions of weight reduction, poor state and the like;
total score: the sum of three scores for skin thickness, crusting and erythema.
As shown in fig. 1, the first, second, third and fourth groups of mice were photographed at day 6, and the second group showed significant erythema, thickening and scaling compared to the first group of ear lesions, demonstrating successful induction of the psoriasis model after imiquimod application. Compared with the second group and the third group, the fourth group has obviously reduced erythema, infiltration and thickening, which indicates that the 4% glutamine physiological saline preparation can effectively treat psoriasis.
As shown in fig. 2, which is a graph of PASI scores from the first day to the sixth day of ear lesions in the first, second, third and fourth groups of mice, it was seen that the 4% glutamine physiological saline formulation was effective in treating psoriasis.
As shown in fig. 3 and 4, HE staining and skin thickness statistics for the sixth day of ear lesions of the first, second, third and fourth groups of mice, it was found that the 4% glutamine physiological saline preparation effectively inhibited keratinocyte proliferation.
As shown in fig. 5, which is a graph of the flow results of ear skin cells of the first, second, third and fourth mice, it can be seen that the second group has significantly increased numbers of mononuclear MDSCs, th1, th17 cells and significantly decreased numbers of Tregs cells, while glutamine significantly inhibits IMQ-induced mononuclear MDSCs, th1 increase and Tregs decrease.
Animal experiment II
The 11 SPF-class (no specific pathogen class experimental animals) BALB/C mice were randomly divided into 3 groups, the first group and the second group of 4, and the third group of 3. The first group is a control group, and does not perform any treatment; the second group is imq+vehicle group, which is fed for 37 days with the physiological saline oral preparation of comparative example 3, and back molding is performed with imiquimod; the third group was imq+4% glutamine group, which was fed with the 4% glutamine physiological saline oral formulation of example 2 for 37 days, and back molding was performed using imiquimod.
After each group of mice is continuously coated for 6 days, the skin damage area and severity index (PASI) of the psoriasis are scored and examined for the psoriasis-like symptoms of the mice, then the mice are killed by weighing and photographing, the skin damage of the ears is taken for HE staining experiments to examine the thickness of the epidermis, namely the proliferation condition of keratinocytes and the quantity change of cells flowing type psoriasis-related immune cells, and meanwhile, the spleen of the mice is taken for weighing and photographing.
As shown in fig. 6, the back photographs of the first, second and third groups of mice on day 6, which showed significant erythema, thickening, scaling in the second group compared to the back skin lesions of the first group, demonstrated successful induction of the psoriasis model after imiquimod application. Compared with the second group, the third group has obviously reduced erythema, infiltration and thickening, which indicates that the 4% glutamine physiological saline oral preparation can effectively treat psoriasis.
As shown in fig. 7, which is a graph of PASI scores from the first day to the sixth day of back lesions in the first, second and third groups of mice, it was seen that the 4% glutamine physiological saline oral formulation was effective in treating psoriasis.
As shown in fig. 8 and 9, which are statistical graphs of HE staining and skin thickness on the sixth day of back skin lesions in the first, second and third groups of mice, it was found that the 4% glutamine physiological saline oral preparation can effectively inhibit keratinocyte proliferation.
As shown in fig. 10, which is a graph of the back skin cell flow results of the first, second and third groups of mice, it can be seen that the number of the second group of mononuclear MDSCs, th1 and Th17 cell populations is significantly increased, while glutamine can significantly inhibit IMQ-induced increase in mononuclear MDSCs and Th 17.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

Claims (10)

1. The application of glutamine as an active ingredient in the preparation of oral therapeutic drugs for psoriasis.
2. The use according to claim 1, wherein the oral psoriasis treating medicament is in the form of a solution.
3. The use according to claim 2, wherein the oral psoriasis treatment drug consists essentially of glutamine and a solvent.
4. The use according to claim 3, wherein the solvent is physiological saline.
5. The use according to claim 2, wherein the concentration of glutamine in the oral psoriasis treatment is between 0.02g/mL and 2g/mL.
6. The use according to claim 2, wherein the concentration of glutamine in the oral psoriasis treatment is 0.04g/mL.
7. The use according to any one of claims 2 to 6, wherein the oral psoriasis treatment medicament further comprises one or more of diluents, preservatives, buffers, antioxidants, suspending agents and colorants.
8. The use according to claim 7, wherein the diluent is selected from one or more of propylene glycol, vegetable oil and mineral oil, the preservative is selected from one or more of sorbic acid, methyl sorbate, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, benzyl parahydroxybenzoate, sodium methyl parahydroxybenzoate, benzoic acid and benzyl alcohol, and the buffer is selected from one or more of sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium citrate, sodium tartrate and sodium acetate.
9. The use according to claim 7, wherein the antioxidant is selected from one or more of ethylenediamine tetraacetic acid, ethylenediamine tetraacetic acid disodium salt, dibutylhydroxytoluene, glycine, inositol, ascorbic acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid and sodium metabisulfite, the suspending agent is selected from one or more of beeswax, ethylhydroxyethyl cellulose, chitin, methylcellulose, carboxymethyl cellulose, agar, hydroxypropyl methyl cellulose and xanthan gum, and the colorant is selected from one or more of carbon black, iron brown, iron red and titanium dioxide.
10. The use according to claim 1, characterized in that the method for the preparation of an oral therapeutic agent for psoriasis comprises the following steps: mixing glutamine with solvent to obtain the oral psoriasis treating medicine.
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