CN117205223A - Application of monogalactosyl diacylglycerol galactolipid in preparation of psoriasis treatment medicine and pharmaceutical composition thereof - Google Patents
Application of monogalactosyl diacylglycerol galactolipid in preparation of psoriasis treatment medicine and pharmaceutical composition thereof Download PDFInfo
- Publication number
- CN117205223A CN117205223A CN202311259066.8A CN202311259066A CN117205223A CN 117205223 A CN117205223 A CN 117205223A CN 202311259066 A CN202311259066 A CN 202311259066A CN 117205223 A CN117205223 A CN 117205223A
- Authority
- CN
- China
- Prior art keywords
- psoriasis
- pharmaceutical composition
- application
- galactolipid
- medicament
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 201000004681 Psoriasis Diseases 0.000 title claims abstract description 46
- 239000003814 drug Substances 0.000 title claims abstract description 31
- FIJGNIAJTZSERN-DQQGJSMTSA-N monogalactosyl-diacylglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)O[C@H](COC(=O)CCCCCCCCCCCC)CO[C@@H]1O[C@@H](CO)[C@H](O)[C@H](O)[C@@H]1O FIJGNIAJTZSERN-DQQGJSMTSA-N 0.000 title claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
- 238000011282 treatment Methods 0.000 title abstract description 14
- 238000002360 preparation method Methods 0.000 title abstract description 13
- 239000006071 cream Substances 0.000 claims abstract description 22
- 210000002510 keratinocyte Anatomy 0.000 claims abstract description 17
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 claims abstract description 10
- 210000003289 regulatory T cell Anatomy 0.000 claims abstract description 8
- 230000007423 decrease Effects 0.000 claims abstract description 6
- 239000004480 active ingredient Substances 0.000 claims description 7
- 206010040882 skin lesion Diseases 0.000 claims description 7
- 231100000444 skin lesion Toxicity 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 238000001565 modulated differential scanning calorimetry Methods 0.000 claims description 5
- 239000011159 matrix material Substances 0.000 claims description 4
- 230000012010 growth Effects 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 abstract description 9
- 238000002474 experimental method Methods 0.000 abstract description 9
- 210000004027 cell Anatomy 0.000 abstract description 8
- 206010015150 Erythema Diseases 0.000 abstract description 7
- 231100000321 erythema Toxicity 0.000 abstract description 7
- 230000008595 infiltration Effects 0.000 abstract description 7
- 238000001764 infiltration Methods 0.000 abstract description 7
- 230000037380 skin damage Effects 0.000 abstract description 7
- 230000035755 proliferation Effects 0.000 abstract description 6
- 230000008719 thickening Effects 0.000 abstract description 6
- 230000009036 growth inhibition Effects 0.000 abstract description 5
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 abstract description 5
- 239000000203 mixture Substances 0.000 abstract description 3
- 210000000068 Th17 cell Anatomy 0.000 abstract description 2
- 230000009982 effect on human Effects 0.000 abstract description 2
- 230000000073 effect on psoriasis Effects 0.000 abstract description 2
- 229930182830 galactose Natural products 0.000 abstract description 2
- -1 galactosyl diacylglycerol Chemical class 0.000 abstract description 2
- 239000013641 positive control Substances 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 21
- 229960002751 imiquimod Drugs 0.000 description 16
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 8
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 8
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000002674 ointment Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229940075507 glyceryl monostearate Drugs 0.000 description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 4
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 4
- 229940012831 stearyl alcohol Drugs 0.000 description 4
- 239000003871 white petrolatum Substances 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 2
- NUZWLKWWNNJHPT-UHFFFAOYSA-N anthralin Chemical compound C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O NUZWLKWWNNJHPT-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- LWQQLNNNIPYSNX-UROSTWAQSA-N calcipotriol Chemical compound C1([C@H](O)/C=C/[C@@H](C)[C@@H]2[C@]3(CCCC(/[C@@H]3CC2)=C\C=C\2C([C@@H](O)C[C@H](O)C/2)=C)C)CC1 LWQQLNNNIPYSNX-UROSTWAQSA-N 0.000 description 2
- 229960002882 calcipotriol Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 229960002311 dithranol Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000003780 keratinization Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 1
- 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
- 206010000349 Acanthosis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940122739 Calcineurin inhibitor Drugs 0.000 description 1
- 101710192106 Calcineurin-binding protein cabin-1 Proteins 0.000 description 1
- 102100024123 Calcineurin-binding protein cabin-1 Human genes 0.000 description 1
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 1
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010033372 Pain and discomfort Diseases 0.000 description 1
- 206010040867 Skin hypertrophy Diseases 0.000 description 1
- 241001464837 Viridiplantae Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940046731 calcineurin inhibitors Drugs 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 230000034659 glycolysis Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000000243 photosynthetic effect Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application provides application of monogalactosyl diacylglycerol galactose in medicaments for treating and improving psoriasis, and a medicinal composition for treating and improving psoriasis. According to the application, the single galactosyl diacylglycerol galactolipid has a growth inhibition effect on human keratinocytes for the first time, animal experiment results show that compared with the back image of a positive control group, the administration group can obviously reduce erythema, infiltration and thickening, effectively inhibit proliferation of the keratinocytes, has a remarkable treatment effect on psoriasis according to the skin damage area and severity index (PASI) score and skin damage HE staining, and can effectively reduce the increase of MDSCs cell population, th1 cell population and Th17 cell population and the decrease of Tregs cell population, so that the MGDG external cream preparation provided by the application can effectively treat psoriasis.
Description
Technical Field
The application relates to application of MGDG (Monogalactosyldiacylglycerol galactolipid) in preparation of a medicament for treating psoriasis and a pharmaceutical composition thereof, and belongs to the field of medicine and pharmacology.
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 their use due to their greater side effects, and the therapeutic effects of 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 selectable external medicine is very limited and is easy to have tolerance, which is always a bottleneck of local treatment of psoriasis, so the development of new medicines for treating psoriasis is significant.
MGDG (monogalactosylated galactosyl ester) was originally isolated from plants more than 40 years ago and represents 80% of membrane lipids in green plant tissue. These lipids are the main components of photosynthetic membranes of higher plants, algae and bacteria, compared to phospholipid-rich animal and yeast cell membranes. In animals, MGDG is present at low concentrations. The basic structure of MGDG is galactose glycerol, which links two fatty acid chains. The research shows that MGDG extracted from plants has antibacterial, antiviral, antitumor and anti-inflammatory activities. (BRUNO A, ROSSI C, MARCLONGO G, et al, select in vivo anti-inflammatory action of the galactolipid monogalactosyldiacylglycerol [ J ]. Eur J Pharmacol 2005,524 (1-3): 159-168.)
The nature of MGDG in disease treatment has not been explored, so its application as a pharmaceutical active ingredient has not been reported, further development of a preparation containing MGDG as an active ingredient is necessary to provide more choices for external medicines for treating psoriasis.
Disclosure of Invention
Aiming at the problems existing in the prior art, one of the purposes of the application is to provide the application of MGDG (Monogalactosyldiacylglycerol galactolipid) in preparing the medicine for treating psoriasis, wherein the structural formula of the MGDG is shown as the formula I:
preferably, the psoriasis is psoriasis vulgaris.
Preferably, the above-mentioned agent is an agent for alleviating and improving psoriasis by inhibiting the growth of keratinocytes.
Preferably, the agents are agents that reduce or ameliorate psoriasis by inhibiting MDSCs, th1, th17 increase, and Tregs decrease.
Preferably, the medicament is for improving skin lesions to reduce and improve psoriasis, more preferably, erythema, infiltration, thickening of the skin.
The second object of the present application is to provide a pharmaceutical composition, wherein MGDG is an active ingredient of the pharmaceutical composition.
Preferably, the above-mentioned medicine is an external medicine; the preferred embodiment is a cream topical medicament.
Preferably, the external medicine further comprises an external matrix, and the MGDG is mixed with the matrix to prepare the external medicine.
More preferably, the base is selected from white petrolatum, stearyl alcohol, glyceryl monostearate, parahydroxybenzoic acid, glycerin, sodium dodecyl sulfate, and water; wherein, white vaseline, stearyl alcohol, glyceryl monostearate and p-hydroxybenzoic acid are used as oil phase, and glycerin, sodium dodecyl sulfate and water are used as water phase.
More preferably, the mass percentage of the active ingredient MGDG in the external medicine is 0.2-98%, and optimally 0.2%.
Terminology
IMQ, imiquimod, imiquimod
PASI: psoriasis area and severity index psoriasis skin lesion area and severity index
MDSCs: myeloid-derived suppressor cells, myeloid-derived suppressor cells
Tregs: regulatory cells
Th1: type 1helper T cells,1 helper T cells
Th17: type 17helper T cells,17 helper T cells
Compared with the prior art, the application discovers that MGDG has growth inhibition effect on human keratinocytes for the first time, and animal experiment results show that compared with the back pictures of a positive control group, the administration group has obvious reduction of erythema, infiltration and thickening, and effectively inhibits the proliferation of keratinocytes, and has obvious treatment effect on psoriasis according to the skin damage area and severity index (PASI) score and skin damage HE staining, and can effectively reduce the increase of MDSCs cell population, th1 cell population and Th17 cell population and the reduction of Tregs cell population, so that the MGDG external cream preparation provided by the application can effectively treat psoriasis. MGDG provides a new direction as a new topical drug for the treatment of psoriasis vulgaris.
Drawings
FIG. 1 is a photograph of the back of each group of mice in the external ointment administration group and the control group obtained in example 1;
FIG. 2 is a graph showing PASI scores from the first day to the seventh day of skin lesions in mice in the IMQ control group and the external ointment administration group obtained in example 1;
FIG. 3 is a graph showing HE staining and skin thickness statistics of the seventh day of back skin lesions of mice in each of the external ointment administration group and the control group obtained in example 1;
FIG. 4 is a graph showing the results of flow-type detection of skin cells on the back of mice in each of the external ointment administration group and the control group obtained in example 1;
FIG. 5 is a graph showing the results of experiments on the therapeutic effects of mice in the external cream administration group and the control group obtained in examples 1 to 5;
FIG. 6 is a photograph of the backs of the mice of the external cream administration groups and the control group obtained in examples 1 to 5;
FIG. 7 is a graph showing comparison of the results of the growth inhibition experiments of human keratinocytes in examples.
Detailed Description
The present application will be described in further detail and in full with reference to the following examples. The following examples are illustrative only and are not to be construed as limiting the application.
The experimental procedures in the examples described below, unless otherwise specified, are generally followed by conventional conditions such as those described in the pharmacological laboratory Manual, third edition, scientific Press, 2002, wherein the methods of Imiquimod (IMQ) modeling and psoriasis efficacy are in accordance with published literature ("Journal of the European Academy of Dermatology and Venereology" Lysophosphatidylcholine facilitates the pathogenesis of psoriasis through activating keratinocytes and T cells differentiation via glycolysis "), or in accordance with the conditions recommended by the manufacturer. Unless otherwise specified, all reagents involved in the examples of the present application are commercially available products and are commercially available.
The main materials related to the embodiment of the application are as follows:
1. experimental animal
BAL B/C male mice of Specific Pathogen Free (SPF) grade, 6-8 weeks in size, and 20-23g in weight, purchased from Hunan Laek's laboratory animal Limited, and kept in the university laboratory animal center in south China. The study has passed the welfare ethics examination of experimental animals at the university of south and middle school. In the experimental process, the method is in line with the principle of '3R', so that the pain and discomfort of animals are reduced as much as possible.
2. Experimental reagent
Example 1
1. Preparation of external cream preparation
1.4 mg of MGDG was weighed out with a weighing paper and dissolved in 20. Mu.L of DMSO to prepare a solution of MGDG for use. Adding 240mg of white vaseline, 160mg of stearyl alcohol, 40mg of glyceryl monostearate and 4mg of p-hydroxybenzoic acid into a beaker, putting into a DF-101S heat-collecting constant-temperature heating magnetic stirrer, heating and dissolving in a water bath at 70 ℃, and stirring for 10 minutes to obtain an oil phase of the cream; simultaneously, 140mg of glycerin, 20mg of sodium dodecyl sulfate and 1.4g of water were added to another beaker and dissolved by heating as well, and stirred for 5 minutes to obtain an aqueous phase of the cream. And slowly adding the water phase into the oil phase, stirring for 10 minutes, slowly adding the MGDG solution, continuously stirring for 3 minutes, standing at room temperature, rapidly stirring to a semisolid state at room temperature by using a glass rod, preparing the 0.2% MGDG cream preparation for treating psoriasis, and bottling for later use.
Examples 2-10 were prepared into creams with the proportions shown in Table 1, respectively, and the preparation method thereof was the same as that of example 1 and will not be described in detail herein.
| Examples | MGDG |
| Example 2 | 0.1％ |
| Example 3 | 0.5％ |
| Example 4 | 2％ |
| Example 5 | 10％ |
Note that: MGDG is percentage.
Comparative example 1
The comparative example differs from example 1 in that MGDG is not added as an active ingredient and the amount of cream adjuvant is the same as that of example 1. Adding white vaseline, stearyl alcohol, glyceryl monostearate and p-hydroxybenzoic acid into beaker at a certain proportion, placing into DF-101S heat collection type constant temperature heating magnetic stirrer, heating in 70deg.C water bath for dissolving, and stirring for 10 min to obtain oil phase of cream; simultaneously, glycerin, sodium dodecyl sulfate and water are added into another beaker according to a certain proportion, and are heated and dissolved in the same way, and are stirred for 5 minutes, so that a water phase of the cream is obtained. The aqueous phase was then slowly added to the oil phase and stirred for 10 minutes, allowed to stand at room temperature and rapidly stirred with a glass rod to a semi-solid state at room temperature to produce a control cream formulation without MGDG.
Animal experiment
The following animal experiments evaluate the remission of Imiquimod (IMQ) induced psoriasis in mice by different percentages of MGDG.
1. Imiquimod (IMQ) modeling
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.
15 BALB/C mice with SPF grade of 6-8 weeks were randomly divided into 3 groups, namely a first group of 6 mice, a second group of 6 mice and a third group of 6 mice, and the back shaving range is 2cm multiplied by 2cm. The treatment modes of each group are as follows:
after each group of mice is continuously coated for 7 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 back 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 for flow type examination of psoriasis-related immune cells, and meanwhile, the spleen of the mice is taken for weighing and photographing.
As shown in fig. 1, which shows the back photo of each group of mice on day 7, the negative control group has obvious erythema, thickening and scaling compared with the back skin damage of the blank control group, and the successful induction of the psoriasis model after imiquimod application is proved. Compared with a negative control group, the administration group has obviously reduced erythema, infiltration and thickening, which indicates that the 0.2% MGDG emulsifiable paste preparation can effectively treat psoriasis.
Fig. 2 is a graph showing PASI scores from day one to day seven of back skin lesions in mice dosed with MGDG from IMQ control, as seen in fig. 2, MGDG cream was effective in treating psoriasis.
Fig. 3 is a graph showing HE staining and skin thickness statistics on day seven of back skin lesions in mice of each group, and as shown in fig. 3, it can be seen that MGDG cream was effective in inhibiting keratinocyte proliferation.
Fig. 4 is a graph showing the results of flow-through detection of skin cells on the back of mice in each group, and as shown in fig. 4, it can be seen that the IMQ control group significantly increases the number of MDSCs cell population, th1 cell population, th17 cell population and the number of Tregs cell population and the MGDG administration group significantly decreases compared with the administration group, and that the MGDG administration group can significantly inhibit IMQ-induced MDSCs, th1, th17 increase and Tregs decrease. Comparison of the therapeutic Effect of creams at different doses
The same experimental methods as described above were used to compare the therapeutic effects of the MGDG creams of examples 2-4, and after 7 days of continuous administration, the 0.1% MGDG cream of example 2 had no significant therapeutic effect, and the doses of the MGDG creams of examples 3-5 were not significantly different from example 1. The specific experimental results are shown in fig. 5 and 6.
Growth inhibition assay of human keratinocytes
Primary keratinocytes were extracted from human foreskin tissue and cultured, 10000 cells per well were inoculated into 96 well plates (keratinocytes were difficult and slow to adhere) after cell growth, 100ul of cell suspension per well was added, 6 compound wells per group, and the same volume of PBS was added to blank wells. Cell proliferation rates were measured at 4 time points of 0 hours, 24 hours, 48 hours, 72 hours. After plating overnight, 0.01uM, 0.1uM, 1uM, and 10uM of MGDG solution (1 mgMGDG was dissolved in 1.3mL DMSO to prepare 1mM of MGDG mother liquor) was added to the cells to adhere to the walls. The absorbance of each well at 450nm wavelength was measured by CCK8 method, and the results are shown in FIG. 7, in which MGDG of 1uM and 10uM has keratinocyte growth inhibition effect as compared with the blank control of 0 uM.
The experimental results show that the treatment of psoriasis can be realized only by 0.2% of MGDG cream, as shown in the experimental results of mice and animals, erythema, infiltration and thickening are obviously reduced, keratinocyte proliferation is inhibited, IMQ-induced MDSCs, th1 and Th17 increase and Tregs decrease are obviously inhibited, and the PASI score proves the effective treatment effect of the psoriasis; in addition, in vitro experiments also prove that MGDG of 1uM and 10uM can inhibit the growth of human keratinocytes; MGDG provides a new direction as a new topical drug for the treatment of psoriasis vulgaris.
Finally, what is necessary here is: the above embodiments are only for further detailed description of the technical solution of the present application, and should not be construed as limiting the scope of the present application, and any person skilled in the art should make some changes, modifications, substitutions, combinations and simplifications by using the technical solution disclosed above without departing from the scope of the technical solution of the present application, all of which are included in the scope of the present application.
Claims (10)
1. The application of the monogalactosyl diacylglycerol galactolipid in preparing a medicament for treating psoriasis is characterized in that the structural formula of the monogalactosyl diacylglycerol galactolipid is shown as formula I:
2. the use according to claim 1, wherein the psoriasis is psoriasis vulgaris.
3. The use according to claim 1, characterized in that the medicament is a medicament for reducing and ameliorating psoriasis by inhibiting the growth of keratinocytes.
4. The use according to claim 1, wherein the medicament is a medicament for reducing and ameliorating psoriasis by inhibiting MDSCs, th1, th17 increase and Tregs decrease.
5. The use according to claim 1, wherein the medicament is for use in improving skin lesions to reduce and ameliorate psoriasis.
6. The pharmaceutical composition is characterized in that the active ingredient of the medicine is monogalactosyl diacylglycerol galactolipid, and the structural formula is shown as formula I:
7. the pharmaceutical composition of claim 6, wherein the pharmaceutical composition is a topical medicament.
8. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is a cream topical drug.
9. The pharmaceutical composition according to claim 6, wherein the mass percentage of the active ingredient monogalactosyl diacylglycerol galactolipid in the external medicament is 0.2-98%.
10. The pharmaceutical composition according to claim 6, wherein the pharmaceutical composition for external use further comprises an external matrix, and wherein the external medicament is prepared by mixing monogalactosyldiacylglycerol galactolipid with the matrix.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311259066.8A CN117205223A (en) | 2023-09-27 | 2023-09-27 | Application of monogalactosyl diacylglycerol galactolipid in preparation of psoriasis treatment medicine and pharmaceutical composition thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311259066.8A CN117205223A (en) | 2023-09-27 | 2023-09-27 | Application of monogalactosyl diacylglycerol galactolipid in preparation of psoriasis treatment medicine and pharmaceutical composition thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117205223A true CN117205223A (en) | 2023-12-12 |
Family
ID=89036907
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311259066.8A Pending CN117205223A (en) | 2023-09-27 | 2023-09-27 | Application of monogalactosyl diacylglycerol galactolipid in preparation of psoriasis treatment medicine and pharmaceutical composition thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117205223A (en) |
-
2023
- 2023-09-27 CN CN202311259066.8A patent/CN117205223A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8586549B2 (en) | Composition and method for modulating and maintaining vaginal bacterial flora and vaginal acidity | |
| RU2671492C2 (en) | Compositions containing berberine or analogs thereof for treating rosacea or red face related skin disorders | |
| NO326139B1 (en) | Composition comprising a plant chemical concentrate of Echinacea purpurea and benzalkonium chloride. | |
| Thakur et al. | Formulation and characterization of benzoyl peroxide gellified emulsions | |
| CN109865160B (en) | Lipid-like liquid crystal compound and preparation method thereof | |
| JP2022546928A (en) | TOPICAL FORMULATIONS CONTAINING CANNABIDIOL, METHODS FOR PREPARATION OF COMPOSITIONS AND USES THEREOF | |
| EA035091B1 (en) | Mixture of fatty acids (gfa, group of fatty acids) and use thereof in the treatment of inflammatory pathologies | |
| WO2020132930A1 (en) | Anti-dandruff anti-itch shampoo composition containing multiple-component zinc | |
| NO320100B1 (en) | Use of a combination of diol and an alpha-hydroxy acid for the treatment of hyperkeratotic skin disorders | |
| CN117205223A (en) | Application of monogalactosyl diacylglycerol galactolipid in preparation of psoriasis treatment medicine and pharmaceutical composition thereof | |
| JP2020536862A (en) | Gluconic acid derivatives for the treatment and / or prevention of microbial infections | |
| KR20020044851A (en) | Sphingolipid composition for preventing or treating acnes | |
| Perl et al. | Vaginal candidiasis: new method of diagnosis and treatment | |
| CN113995763B (en) | Application of phosphatidylethanolamine as active ingredient in preparation of psoriasis treatment medicine, psoriasis treatment medicine and preparation method thereof | |
| CN117679411A (en) | Application of ATX inhibitor in preparation of psoriasis treatment medicine and pharmaceutical composition thereof | |
| WO2020232181A1 (en) | Compositions comprising plant extracts and oils and related methods of treatment and their preparation | |
| CN110693947A (en) | Gel preparation for treating skin diseases and preparation method thereof | |
| CN117679416A (en) | Application of ATX inhibitor in preparation of psoriasis treatment medicine and pharmaceutical composition thereof | |
| JPH08109128A (en) | Preparation for treating allergic dermatopathy for external use | |
| CN110693819B (en) | Pharmaceutical composition for preventing and treating acarid dermatitis and preparation method thereof | |
| WO2018197668A1 (en) | Skin care composition | |
| CN107115383A (en) | With the skin care/therapeutic combination for preventing and treating dry skin syndrome effect | |
| RU2486911C1 (en) | Agent for vaginal douche in phase of vaginal microflora recovery following treatment of bacterial vaginosis and vaginal thrush (vaginal yeast) | |
| KR101924355B1 (en) | Composition for anti-stretch mark effect on the skin containing extracts of salicornia herbacea and ecklonia cava | |
| JP7396585B2 (en) | Composition for suppressing TSLP gene expression, suppressing IL-33 gene expression, or promoting filaggrin production |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |