CN110840878B - Compound for treating psoriasis and preparation method thereof - Google Patents
Compound for treating psoriasis and preparation method thereof Download PDFInfo
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- CN110840878B CN110840878B CN201911064900.1A CN201911064900A CN110840878B CN 110840878 B CN110840878 B CN 110840878B CN 201911064900 A CN201911064900 A CN 201911064900A CN 110840878 B CN110840878 B CN 110840878B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/02—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the alkali- or alkaline earth metals or beryllium
- B01J23/04—Alkali metals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
Abstract
The invention provides application of α -pyrone derivative 6- (3-hydroxypent-1-alkenyl) -2H-pyran-2-one in treating psoriasis and a pharmaceutical composition containing the compound, and further provides a chemical preparation method of 6- (3-hydroxypent-1-alkenyl) -2H-pyran-2-one, which has the advantages of simple operation, high product yield and low cost, can realize large-scale production, and solves the problems of complicated steps, low product yield and difficulty in large-scale preparation of the existing biological preparation method.
Description
Technical Field
The invention relates to the field of medicines, in particular to a compound for treating psoriasis, and also relates to a preparation method of the compound.
Background
Psoriasis (psoriasis) is an immune-mediated chronic inflammatory skin disease, and the pathological features of the psoriasis include abnormal proliferation of epidermal keratinocytes, infiltration of dermal lymphocytes and vascular proliferative changes, and erythema, scaling, pruritus and other symptoms at affected parts. Psoriasis varies in severity from mild, localized plaques to complete body coverage. Common forms of the disease include, for example, plaque psoriasis, guttate psoriasis, reverse psoriasis, pustular psoriasis, and erythrodermic psoriasis. The cause of psoriasis is not clear, but is believed to be hereditary, which may be exacerbated by a variety of factors, such as stress, withdrawal from systemic corticosteroids, excessive alcohol consumption and smoking.
Psoriasis is difficult to treat, and at present, although some treatments exist, certain disadvantages exist. For example, topical treatments with anthratriphenol (dithranol), topicot, foscarnet, vitamin D analogs (e.g., calcipotriol), retinoids, etc., often irritate normal skin and thus are not useful for extended periods of time, and may lead to repeated disease after withdrawal. Psoriasis can also be treated by systemic treatment, by injection or oral administration of drugs such as methotrexate, cyclosporine and retinoids. However, these drugs are known to have toxic side effects and therefore cannot be used too frequently. At the same time, patients receiving systemic treatment also need regular blood and liver function tests, and most of these treatments must avoid pregnancy. Psoriasis recurrences occur in most people after discontinuation of systemic treatment.
In addition, there are light therapies, such as daily, brief non-burning sun or ultraviolet B (UVB) (315) and 280nm radiation, that help to clear or ameliorate psoriasis in some (but not all) patients. Photochemotherapy, a combination therapy of psoralen and ultraviolet a Phototherapy (PUVA), has also been used to treat psoriasis. However, PUVA is associated with nausea, headache, fatigue, burning, itching. Chronic PUVA treatment may also lead to squamous cell carcinoma association. In addition, biological agents such as anti-IL-12 and IL-23 drugs, Ultezumab, and anti-IL-17 monoclonal antibody drug, secukinumab, can be used, but they are also too expensive.
Therefore, development of more effective, low-toxicity and cheap anti-psoriasis medicines is urgently needed to meet the market demand and provide a new strategy for treating psoriasis.
α -pyrone derivatives are important organic heterocyclic compounds, widely exist in natural products, and many of them show good physiological activities, such as anti-HIV, anti-bacteria, anti-fungi, anti-leukemia, anti-tumor, etc., and have very wide application in medicine and pesticide, CN104211670B reports an alkenyl pyrone compound, its chemical name is 6- (3-hydroxypent-1-alkenyl) -2H-pyran-2-one:
the compound is separated from fermentation mycelium of Trichoderma asperellum (Trichoderma asperellum), and has antitumor activity, especially inhibitory activity on RAJI of human lymph cancer cell. In the course of the research, the applicant has unexpectedly found that the compound has excellent effects in treating psoriasis, and has proposed the present invention. In addition, the invention also provides a chemical preparation method of the compound, in view of the complicated steps of the biological preparation method of CN104211670B, particularly the low yield of the product caused by multiple chromatographic column separations and the difficulty in realizing large-scale production.
Disclosure of Invention
The invention aims to provide an application of α -pyrone compound in treating psoriasis, and in addition, the invention aims to provide a novel preparation method of the compound.
According to one aspect of the invention, the α -pyrone compound is 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one, which has the following structure:
it is a further object of the present invention to provide a process for the chemical preparation of said 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one, which comprises the steps of:
wherein step 1 is carried out in the presence of a solid base catalyst; step 2 is carried out in the presence of zinc powder.
In one embodiment, the solid base catalyst is a base supported on alumina, the base being selected from sodium hydroxide, potassium hydroxide or cesium hydroxide; the solid base catalyst is preferably sodium hydroxide supported on alumina.
In one embodiment, the zinc powder is an activated zinc powder.
In one embodiment, the solid base catalyst is obtained by impregnating an aqueous solution of sodium hydroxide, potassium hydroxide or cesium hydroxide onto alumina, followed by drying and calcination.
The invention further provides a method of treating psoriasis comprising administering to a patient in need thereof an effective amount of 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one, or a pharmaceutically acceptable salt thereof.
The invention further provides a method of treating psoriasis comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition comprising 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or adjuvant.
The invention further provides the use of 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of psoriasis.
The invention further provides a pharmaceutical composition comprising 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or adjuvant.
As used herein, the following words, phrases and symbols are generally intended to have the meanings as set forth below, unless they are used in context to denote other meanings. The following abbreviations and terms have the indicated meanings throughout.
The term "psoriasis" as used herein refers to a condition in which cells rapidly accumulate on the skin surface, forming thick silvery scales and sometimes painful itchy, dry, red plaques or plaques. In one embodiment, the psoriasis is an autoimmune disorder. In one embodiment, the psoriasis comprises plaque psoriasis, guttate psoriasis, reverse psoriasis, pustular psoriasis, and erythrodermic psoriasis.
The term "patient" as used herein refers to an individual suffering from a disease, disorder or condition, and the like, including mammals and non-mammals. Examples of mammals include, but are not limited to, any member of the class mammalia: humans, non-human primates (e.g., chimpanzees and other apes and monkeys); livestock, such as cattle, horses, sheep, goats, pigs; domestic animals such as rabbits, dogs, and cats; laboratory animals, including rodents, such as rats, mice, and guinea pigs, and the like. Examples of non-human mammals include, but are not limited to, birds, fish, and the like. In one embodiment related to the methods and compositions provided herein, the mammal is a human.
As used herein, the term "treating" and other similar synonyms include alleviating, or ameliorating a symptom of a disease or disorder, preventing other symptoms, ameliorating, or preventing an underlying metabolic cause of a symptom, inhibiting a disease or disorder, e.g., arresting the development of a disease or disorder, alleviating a disease or disorder, ameliorating a disease or disorder, alleviating a symptom of a disease or disorder, or discontinuing a symptom of a disease or disorder, and further, the term encompasses prophylactic purposes. The term also includes obtaining a therapeutic effect and/or a prophylactic effect. The therapeutic effect refers to curing or ameliorating the underlying disease being treated. In addition, a cure or amelioration of one or more physiological symptoms associated with the underlying disease is also a therapeutic effect, e.g., an improvement in the condition of the patient is observed, although the patient may still be affected by the underlying disease. For prophylactic effect, the composition can be administered to a patient at risk of developing a particular disease, or to a patient presenting with one or more physiological symptoms of the disease, even if a diagnosis of the disease has not yet been made.
The term "effective amount" as used herein refers to an amount of at least one agent or compound sufficient to alleviate to some extent one or more of the symptoms of the disease or condition being treated upon administration. The result may be a reduction and/or alleviation of signs, symptoms, or causes, or any other desired change in a biological system. For example, an "effective amount" for treatment is the amount of a composition comprising a compound disclosed herein that is clinically necessary to provide a significant remission effect of the condition. An effective amount suitable in any individual case can be determined using techniques such as a dose escalation assay.
The term "acceptable" as used herein means that there is no long-term detrimental effect on the general health of the subject being treated.
The term "pharmaceutically acceptable" as used herein refers to a substance (e.g., carrier or adjuvant) that does not affect the biological activity or properties of the compounds of the present application, and is relatively non-toxic, i.e., the substance can be administered to an individual without causing an adverse biological response or interacting in an adverse manner with any of the components contained in the composition.
The terms "administration," "administering," and the like as used herein refer to a method capable of delivering a compound or composition to a desired site for biological action.
It will be appreciated that the pharmaceutical compositions for use according to the invention may be in the form of suspensions, capsules or tablets for oral, parenteral, transdermal, sublingual, topical, implantation, nasal or enteral administration (or other mucosal administration), which may be formulated in conventional manner using one or more pharmaceutically acceptable carriers or adjuvants. The pharmaceutical compositions of the present invention may also be formulated as nanoparticle formulations.
However, for the treatment of psoriasis, the pharmaceutical composition of the invention is preferably administered topically. Thus, the pharmaceutical composition of the present invention may be provided in the form of a cream, ointment, gel, transdermal formulation, foam, spray, lotion, solution, emulsion or suspension, preferably in the form of a cream, ointment, gel, transdermal formulation, more preferably in the form of a cream.
In one embodiment of the present invention, the pharmaceutical composition may comprise a solubilizing agent and a penetration enhancer. In a preferred embodiment, the solubilizing agent according to the present invention includes, but is not limited to, dimethyl malonate, diethyl succinate, diethyl glutarate, diethyl adipate, dipropyl adipate, dibutyl sebacate, diisopropyl sebacate, diethyl pimelate, diethyl suberate, diethyl azelate, dibutyl adipate, dibutyl sebacate, ethyl methyl succinate, diethyl ethyl isopropyl malonate, diethyl isobutyrate, benzyl alcohol, benzyl benzoate, cyclodextrin, glycerol monostearate, lecithin, butylene glycol, dibutyl phthalate, diethyl phthalate, dimethyl ether, diethyl ether, ethyl acetate, ethyl lactate, ethyl oleate, glycerol triacetate, triethanolamine, hexylene glycol, dimethyl sulfoxide, and/or dimethyl isosorbide. Isosorbide dimethyl ether is preferably used. The solubilizer according to the invention is present in an amount ranging from 5 to 30% by weight of the composition. Preferably, it is present in an amount in the range of 5 to 25 wt% of the composition.
Penetration enhancers act by various mechanisms to reduce the skin barrier and accelerate absorption of the drug through the skin in a preferred embodiment, penetration enhancers according to the present invention include, but are not limited to, alcohols such as 1-butanol, 1-pentanol, 1-hexanol, 1-octanol, benzyl alcohol, 2-phenylethanol, ethanol, isopropanol, decanol, octanol, hexylene glycol, butylene glycol, pyrrolidones such as 1-ethyl-2-pyrrolidone, 1-butyl-2-pyrrolidone, 1-hexyl-2-pyrrolidone, 1-octyl-2-pyrrolidone, 1-decyl-2-pyrrolidone, 1-dodecyl-2-pyrrolidone, N-methyl-2-pyrrolidone, azones such as 1-butyl-2-azenone, 1-hexyl-2-azenone, 1-octyl-2-azenone, 1-dodecyl-azepan-2-one (laurocapram), fatty acids such as eucalyptus, undecanoic acid, lauric acid, tridecanoic acid, myristic acid, palmitic acid, stearic acid, polyoxyethylene glycol mono-2-polyoxyethylene sorbitan, polyoxyethylene sorbitan-2-polyoxyethylene sorbitan-2-polyoxyethylene sorbitan-polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene sorbitan-polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene sorbitan-polyoxyethylene, polyoxyethylene sorbitan-polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene-polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene-polyoxyethylene ether, polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene-polyoxyethylene glycol, polyoxyethylene-polyoxyethylene ether, polyoxyethylene glycol, polyoxyethylene ether, polyoxyethylene-polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene sorbitan-polyoxyethylene ether, polyoxyethylene-polyoxyethylene ether, polyoxyethylene glycol polyoxyethylene-polyoxyethylene glycol polyoxyethylene-polyoxyethylene ether.
The pharmaceutical compositions of the present invention also comprise one or more pharmaceutical adjuvants, including, but not limited to, oily bases, absorbent bases, emulsifiers, preservatives, antioxidants, surfactants, emollients, humectants, gelling agents, thickeners, hardeners, viscosity increasing agents, film forming agents, foam forming agents, stabilizers, buffers, pH adjusting agents, suspending agents, solvents, co-solvents, crystal growth inhibitors, diluents, chelating agents, vehicles, colorants and/or fragrances.
The pH of the composition according to the invention is in the range of 3 to 7, preferably 4 to 6. Suitable pH adjusting agents may be added to the composition to maintain the desired pH.
The pharmaceutical compositions of the invention may contain 0.01 to 99 wt% of the active substance. The therapeutic dose is generally about 10 to 2000 mg/day, preferably about 30 to 1500 mg/day of the combined active ingredients. Other ranges may be used including, for example, 50-500 mg/day, 50-300 mg/day, 100-200 mg/day or combinations of active ingredients.
Administration may be once daily, twice daily, or more often, and may be reduced during the maintenance period of the disease or condition, e.g., once every other day or every third day, rather than once daily or twice daily. The dosage and frequency of administration will depend on the clinical signs of maintenance of the confirmed remission period, the reduction or absence of at least one or more, preferably more than one, clinical symptoms of the acute phase as known to those of skill in the art.
Advantageous effects
(1) The application discovers that the 6- (3-hydroxypent-1-alkenyl) -2H-pyran-2-ketone has excellent effect on treating psoriasis, and experiments show that the 6- (3-hydroxypent-1-alkenyl) -2H-pyran-2-ketone has excellent inhibition effect on human immortalized epidermal (HaCat) cells and also has very good prevention and treatment effect on the psoriasis induced by propranolol hydrochloride. Thus, 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one is particularly suitable for the treatment of psoriasis.
(2) In the preparation method of 6- (3-hydroxypent-1-alkenyl) -2H-pyran-2-ketone, the solid base catalyst is adopted in the step 1, so that the side reaction of the condensation reaction is less, the reaction is mainly cross condensation, the phenomenon of self-polymerization of aldehyde or ketone is inhibited, the impurities are less, and the product can be directly used for the next reaction after simple treatment; in step 2, activated zinc powder is used as a reducing agent, and ketones can be selectively reduced without reducing double bonds or esters. Therefore, the preparation method provided by the invention is simple to operate, high in product yield and low in cost, can realize large-scale production, and overcomes the problems that the existing biological preparation method is complicated in steps, low in product yield and difficult to prepare in large quantities.
Detailed Description
The present invention will now be described in further detail with reference to the following specific examples, which should not be construed as in any way limiting the scope of the invention.
Those skilled in the art will recognize that: the chemical reactions described herein may be used to suitably prepare a number of other compounds of the invention, and other methods for preparing the compounds of the invention are considered to be within the scope of the invention. In addition, the reactions disclosed herein or known reaction conditions are also recognized as being applicable to the preparation of other compounds of the present invention.
Example 1-preparation example:
step 1: preparation of solid base catalyst
Dissolving 2.0g of sodium hydroxide in deionized water, soaking 40.0g of gamma-alumina in the same volume for 24 hours, drying at 130 ℃ for 15 hours, and roasting at 600 ℃ for 4 hours to obtain the solid base catalyst with sodium hydroxide loaded on the aluminaAgent NaOH/Al2O3。
Step 2: preparation of 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one
Mixing methyl ethyl ketone (5ml), the catalyst (8.4g) prepared in step 1 and ethanol (60ml), then dropwise adding a solution of 2H-pyran-2-one (1.24g, 10mmol) dissolved in ethanol (20ml), reacting after 10 minutes of dropwise addition, stirring at room temperature, monitoring by TLC, after the starting point of 2H-pyran-2-one completely disappeared, heating the solution to 45 ℃ to continue reacting for 1-2 hours, so that the reaction was completely carried out, cooling and filtering to remove insoluble substances, adjusting the pH of the filtrate to about 4.5 with 1M HCl solution, then adding water (200ml) to dilute, extracting with ethyl acetate (200ml × 2) and merging the organic layers, washing twice with saturated saline and deionized water, drying with anhydrous sodium sulfate, removing the solvent by vacuum rotary evaporation, and dissolving in dried ether solution (30ml) for later use.
Activated zinc powder (1.3g) was dispersed in dry ether solution (30ml), a little iodine element was added, and the solution was stirred until colorless. Slowly dripping the prepared standby solution in the step under the condition of vigorous stirring, and refluxing under stirring for reaction. The reaction was monitored by TLC until the reaction was complete. After cooling, insoluble matter was removed by filtration, the filtrate was diluted with ethyl acetate, washed with 1M HCl, washed twice with saturated brine and deionized water, and the solvent was removed by rotary evaporation in vacuo. The residue was purified by column chromatography on silica gel (mobile phase: ethyl acetate/petroleum ether: 1:99 to 5:99, gradient elution). The obtained product was recrystallized from ethanol to obtain 1.57g of colorless crystals, with a yield of 87.4%.
ESI-MS m/z＝203.07[M+Na]+
Hydrogen spectrum (400MHz, DMSO-d)6)δ7.55(dd,1H),6.50(dd,1H),6.38(d,1H),6.33(dd,1H),6.20(d,1H),4.02(m,1H),1.54(m,1H),1.44(m,1H),0.88(t,3H)。
The characterization results are consistent with those reported in the literature, and prove that the method can prepare the 6- (3-hydroxypent-1-alkenyl) -2H-pyran-2-ketone with high yield and is easy to realize large-scale production.
Example 2 formulation example
The formulation of the preparation is as follows:
| 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one | 1g |
| Isosorbide dimethyl ether | 5g |
| Diethylene glycol monoethyl ether | 3g |
| Liquid paraffin | 8g |
| Polyethylene glycol-7-stearate | 10g |
| Dibutylhydroxytoluene | 0.1g |
| Propylene glycol | 20g |
| Triethanolamine | 10g |
| Purified water | To 100g |
The preparation method comprises the following steps:
dissolving 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one in propylene glycol, adding isosorbide dimethyl ether, diethylene glycol monoethyl ether, dibutyl hydroxy toluene, triethanolamine and purified water, stirring uniformly, and heating to 70-80 ℃ to form a water phase; heating liquid paraffin and polyethylene glycol-7-stearate to 70-80 deg.C to form oil phase; adding the water phase into the oil phase to form a cream, stirring, and slowly cooling to room temperature to obtain a cream containing 1 wt% of 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one.
In a similar manner, a cream containing 0.5%, 2%, 3% by weight of 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one was prepared.
Example 3-pharmacological activity test example:
1. in vitro MTT assay
6- (3-hydroxypent-1-enyl) -2H-pyran-2-one was dissolved in dimethyl sulfoxide and was diluted with a PBS buffer gradient to prepare solutions having concentrations of 1000. mu.g/ml, 100. mu.g/ml, 10. mu.g/ml, 1. mu.g/ml, 0.1. mu.g/ml and 0.01. mu.g/ml, respectively. The sample solution was added to a 96-well plate in which human immortalized epidermal (HaCat) cells in the growth phase (pharmaceutical laboratory, shanghai institute of pharmaceutical industry) were placed and cultured for 48 hours. Inhibitory activity was then determined by the standard MTT method, where four replicates were set at each concentration, each set of experiments was replicated 3 times, and conclusions were drawn from blank group comparisons. And detecting the OD value of each hole by using a microplate reader, wherein the detection wavelength is 570 nm. The cytostatic rate was calculated as follows:
then, the logarithmic value of the sample concentration and the cell inhibition ratio were linearly regressed, and the half-inhibitory concentration IC of the sample on the cells was calculated by using software50The value is obtained. As a result, the inhibitory activity of 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one against human immortalized epidermal (HaCat) cells was IC50＝54μg/ml。
2. Propranolol hydrochloride-induced psoriasis model in guinea pigs
60 guinea pigs were taken and randomized into 6 groups: (1) a saline control group, (2) a blank cream group, and (3) four test groups. Of these, the blank cream group and four test groups were applied evenly to the back of both ears with 5% propranolol hydrochloride cream (about 200 μ l) twice daily for four consecutive weeks. The saline control group was treated with saline on the back of both ears (200. mu.l) twice a day. The administration was started four weeks later, and the normal saline control group continued to apply the normal saline; the blank cream group is administered using the blank cream; four test groups were dosed as creams using 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one at concentrations of 0.5 wt%, 1 wt%, 2 wt%, 3 wt%. The administration was performed twice daily for 7 consecutive days. Guinea pigs were examined during the experiment and sacrificed 1 hour after the last dose, and their thickness of the ear epidermis was measured. The results of the experiments are reported in table 1 below.
Table 1: results of the experiment with psoriasis model in guinea pig
| Group of | Skin thickness (μm) |
| Physiological saline control group | 54.22±3.15## |
| Blank cream control group | 240.48±15.27** |
| Test group 0.5 wt% | 194.75±12.59**# |
| Test group 1 wt% | 170.46±10.65**## |
| Test group 2 wt% | 157.18±9.47**## |
| Test group 3 wt% | 129.85±7.21**## |
Note: p compared to saline control group<0.05，**P<0.01; compared with the blank cream control group,#P<0.05，##P<0.01
the test results show that the 6- (3-hydroxypent-1-alkenyl) -2H-pyran-2-ketone has very excellent inhibitory action on human immortalized epidermal (HaCat) cells; meanwhile, the composition has very good prevention and treatment effects on the propranolol hydrochloride-induced psoriasis in a guinea pig test. This suggests that 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one has an excellent psoriasis-treating effect and is particularly suitable for treating psoriasis.
The foregoing describes preferred embodiments of the present invention, but is not intended to limit the invention thereto. Modifications and variations of the embodiments disclosed herein may be made by those skilled in the art without departing from the scope and spirit of the invention.
Claims (4)
- Use of 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of psoriasis, the 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one having the structure:
- 2. the use according to claim 1, wherein the medicament is a pharmaceutical composition prepared from 6- (3-hydroxypent-1-enyl) -2H-pyran-2-one or a pharmaceutically acceptable salt thereof as an active ingredient together with a pharmaceutically acceptable carrier or adjuvant.
- 3. Use according to claim 2, wherein the pharmaceutical composition is provided in the form of a cream, ointment, gel, transdermal formulation, foam, spray, lotion, solution, emulsion or suspension.
- 4. Use according to claim 2, wherein the pharmaceutical composition comprises a solubilizer and a penetration enhancer.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101534806A (en) * | 2006-11-07 | 2009-09-16 | 爱尔康研究有限公司 | Method of treating asthma, allergic rhinitis, and skin disorders |
| CN104211670A (en) * | 2013-05-30 | 2014-12-17 | 福州大学 | Alkyl pyranone compound and preparation process and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101534806A (en) * | 2006-11-07 | 2009-09-16 | 爱尔康研究有限公司 | Method of treating asthma, allergic rhinitis, and skin disorders |
| CN104211670A (en) * | 2013-05-30 | 2014-12-17 | 福州大学 | Alkyl pyranone compound and preparation process and application |
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