Pharmaceutical composition for treating palmoplantar keratosis and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and provides a pharmaceutical composition which is used for treating palmoplantar keratosis and is characterized by comprising the following components in parts by weight: 10-15 parts of zinc oxide, 0.05-0.1 part of gentamicin sulfate, 0.5-1 part of thymol, 10-20 parts of Arabic gum and 10-20 parts of modified starch. The pharmaceutical composition provided by the invention can achieve a relatively high treatment effective rate on palmoplantar keratosis.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular relates to a pharmaceutical composition for treating palmoplantar keratoderma and a preparation method thereof. Background Art

[0002] Palmoplantar keratoderma (PPK) is a group of heterogeneous skin diseases characterized by abnormal thickening and hyperkeratosis of the skin on the palms and soles. It can be divided into acquired palmoplantar keratoderma and hereditary palmoplantar keratoderma. Acquired palmoplantar keratoderma is more common in clinical practice. Acquired PPK can be caused by inflammatory diseases, such as psoriasis, eczema, and various chronic hand and foot skin diseases, as well as trauma, infection, systemic diseases, tumors, etc.; hereditary PPK is rare in clinical practice, and the disease occurs shortly after birth. It is characterized by symmetrical hyperkeratosis of the skin on the palms and soles, and is inherited in an autosomal dominant or recessive manner; palmoplantar keratoderma can affect only the skin on the palms and soles, or it can affect the skin outside the palms and soles. When it is not accompanied by lesions of other organs and systems, it is non-syndromic PPK (also called isolated PPK); and some palmoplantar keratoderma can be accompanied by lesions of other organs or systems, which is called syndromic palmoplantar keratoderma (also called non-isolated PPK).

[0003] Diffuse PPK is the most common type of PPK. The lesions involve the entire palm and sole area and are diffusely distributed. Some subtypes of lesions may involve other parts of the body except the palm and sole. Diffuse PPK is divided into many subtypes according to the severity, area of ​​lesions, pathological manifestations and inheritance pattern. Diffuse PPK caused by mutations in the KRT9 and KRT1 genes is the most common. The KRT9 and KRT1 genes encode keratins K9 and K1, respectively. Heterozygous mutations of these two genes can lead to three different types of diffuse palmoplantar keratoderma, including epidermolytic palmoplantar keratoderma, Greither palmoplantar keratoderma and non-epidemolytic palmoplantar keratoderma (NEPPK). In addition, Nagashima palmoplantar keratoderma and Mal de Meleda disease, which are caused by mutations in the SERPINB7 and SLURP1 genes, respectively, are also diffuse PPK.

[0004] Epidemolysis palmoplantarkeratoderma (EPPK), caused by KRT9 gene mutation, was first reported by Vorner in 1901 and is the most common subtype of diffuse PPK. EPPK is inherited in an autosomal dominant manner and develops soon after birth. Clinical manifestations include diffuse yellow hyperkeratosis of the skin on the palms and soles, with clear erythema as the boundary at the palmar edge. The pathological manifestations of EPPK are epidermolysis hyperkeratosis, perinuclear vacuolation, large keratinous transparent granules and cell degeneration in the spinous and granular layers, which are characteristic. The KRT9 gene is only expressed in the skin of the hands and feet, so an important feature of EPPK caused by gene mutation is that the skin lesions only affect the palms and soles, without crossing the line. Gene mutation can also lead to the occurrence of EPPK, but it is often accompanied by crossing the line, and the skin lesions can affect the back of the hand, the back of the foot, and the skin of the Achilles tendon.

[0005] SERPINB7 gene mutations can lead to Nagashima palmoplantar keratoderma (NPPK), which is inherited in an autosomal recessive manner. This subtype is clinically rare and was first reported by Nagashima in 1977. Nagashima PPK is relatively common in Asian populations, with more reports in Korea, China, Japan, etc. The clinical manifestations are diffuse erythema, hyperkeratosis, accompanied by line-crossing behavior. The lesions can extend to the back of the hands, the back of the feet, and even the Achilles tendon, elbows and knees. Hyperhidrosis of the hands and feet can be seen, and the lesions do not develop progressively. The erythematous keratotic lesions of NPPK can turn white after being immersed in water for ten minutes.

[0006] Mal de Meleda (MDM) disease, which is inherited in an autosomal recessive manner and caused by mutations in the SLURP1 gene, was first discovered by Luca Stulli in 1826 and named by Hovorka and Ehlers in 1897. The clinical manifestations of MDM disease are well-defined palmoplantar hyperkeratosis that appears shortly after birth. The lesions are dark yellow in color, waxy in texture, surrounded by erythema, and accompanied by line-crossing behavior. The skin lesions of MDM disease develop progressively, and hyperkeratotic plaques on the elbows and knees, nail dystrophy, perioral erythema, short and tapered fingers, and rare finger contraction rings and spontaneous amputations may occur. Patients with MDM disease also often have hyperhidrosis in the hands and feet. When combined with bacterial or fungal infections, there may be a foul odor, and the range of motion of the hands and feet is usually reduced, and the clinical symptoms are more severe.

[0007] Focal PPK caused by mutations in the KRT16 gene is inherited in an autosomal dominant pattern and was first defined by Gorlin in 1976. It is relatively rare. The occurrence of focal PPK is significantly related to friction pressure. Usually, the skin symptoms on the palms are milder, while the keratotic lesions on the pressure sites on the soles are more severe and painful, which may be accompanied by mild nail lesions. The histopathological characteristics of focal PPK are hyperkeratosis, thickening of the granular and spinous layers, and no epidermolytic changes. Focal skin hyperkeratosis and oral leukoplakia often coexist in pachyonychia congenita (PC).

[0008] PPK of the striae type is mainly linearly distributed in the palms and focally or diffusely distributed in the soles. It is caused by mutations in the DSG1 and DSP genes. DSG is a desmosomal transmembrane cadherin that is essential for ensuring intercellular adhesion in the skin (DSG1-3), hair follicles (DSG4), and myocardium (DSG2); mutations in the DSG1 gene can lead to impaired desmosome function, with the palms and soles being the most affected areas. The histopathological features of PPK of the striae type include widening of the intercellular spaces in the epidermis and disruption of intercellular junctions (acantholysis). PPK of the punctate type presents as hyperkeratotic papules that occur symmetrically on the palms and soles. It is characterized by hyperkeratotic, centrally depressed papular lesions that are irregularly distributed on the palms and soles and merge into yellow plaques in areas of greater pressure and friction. Summary of the invention

[0009] The purpose of the present invention is to provide a pharmaceutical composition for treating palmoplantar keratoderma.

[0010] To achieve the above-mentioned purpose of the invention, the technical solution of the present invention is as follows:

[0011] According to a first aspect of the present invention, a pharmaceutical composition is provided, comprising, by weight: 10-15 parts of zinc oxide, 0.05-0.1 parts of gentamicin sulfate, 0.5-1 parts of thymol, 10-20 parts of gum arabic and 10-20 parts of modified starch.

[0012] In one aspect of the present invention, the pharmaceutical composition further comprises, by weight: 1-3 parts of phenol, 1.5-5 parts of sodium carboxymethyl cellulose and 5-15 parts of glycerol.

[0013] In one aspect of the present invention, the pharmaceutical composition comprises, by weight: 12-15 parts of zinc oxide, 0.06-0.1 parts of gentamicin sulfate, 0.6-1 parts of thymol, 15-20 parts of gum arabic, 15-20 parts of modified starch, 1.6-3 parts of phenol, 2.5-5 parts of sodium carboxymethyl cellulose and 10-15 parts of glycerol.

[0014] In one aspect of the invention, the pharmaceutical composition is prepared in the form of a liquid suspension. The liquid solvent of the pharmaceutical composition of the present invention may include the components described for the liquid suspension. Aqueous solvents include, for example, water and isotonic saline. Oily solvents include, for example, almond oil, oily esters, ethanol, vegetable oils such as peanut oil, olive oil, sesame oil or coconut oil, fractionated vegetable oils and mineral oils such as liquid paraffin.

[0015] In one aspect of the invention, the pharmaceutical composition is a cream, ointment, lotion, powder, liniment, gel, foam, solution, suspension, emulsion, paste or aerosolized mixture.

[0016] In one aspect of the invention, the pharmaceutical composition is a lotion.

[0017] According to a second aspect of the present invention, there is provided a method for preparing the aforementioned pharmaceutical composition, wherein the pharmaceutical composition is a lotion, and the method comprises the following steps:

[0018] In a dry environment, zinc oxide, gentamicin sulfate, gum arabic and modified starch are put into a grinder and grind to obtain a mixed powder;

[0019] The mixed powder is transferred to a container, and thymol, phenol and sodium carboxymethyl cellulose are dissolved in water to obtain a thymol solution, a phenol solution and a sodium carboxymethyl cellulose solution respectively;

[0020] The thymol solution, the phenol solution and glycerin are added to the mixed powder and ground until uniform; a uniformly ground mixture is obtained, and then the sodium carboxymethyl cellulose solution is added to the uniformly ground mixture, and after sufficient mixing, water is added to the prescribed amount; the lotion is obtained.

[0021] In one aspect of the present invention, the palmoplantar keratoderma includes hereditary palmoplantar keratoderma and acquired palmoplantar keratoderma.

[0022] In one aspect of the present invention, the hereditary palmoplantar keratoderma includes hereditary diffuse palmoplantar keratoderma and hereditary focal palmoplantar keratoderma.

[0023] In one aspect of the present invention, the hereditary diffuse palmoplantar keratoderma includes variable erythematous keratoderma, Sybert's palmoplantar keratoderma, Olmsted syndrome and Naegeli-Franceschetti-Jadassohn syndrome.

[0024] In one aspect of the invention, the pharmaceutical composition is topically applied to the skin on the hands and / or feet.

[0025] In one aspect of the invention, the specific dosage and dosage range that can be used depend on various factors, including the patient's needs, the severity of the disease being treated, and the pharmacological activity of the compound being administered. According to the disclosure of the present invention, the determination of the dosage range and optimal dose for a specific patient is completely within the ordinary skill of those skilled in the art. It should be understood that ordinary physicians will be easy to determine and prescribe effective doses of compound prescriptions. In the foregoing, the physician can, for example, first prescribe a lower dosage, and then increase the dosage until an appropriate response is obtained. However, it should also be understood that the specific dosage level for any particular individual will depend on various factors, including the activity of the specific compound used, the age, weight, general health, sex and diet of the person, the time of administration, any drug combination of the route of administration, and the severity of the disorder being treated.

[0026] In one aspect of the present invention, the pharmaceutical composition may also include one or more pharmaceutically suitable excipients, such as solvents and co-solvents, solubilizers, co-solvents, wetting agents, suspending agents, thickeners, emulsifiers, chelating agents, buffers, pH regulators, antioxidants, reducing agents, antimicrobial preservatives, extenders, protective agents, tension regulators and special additives.

[0027] The beneficial effect of the present invention is that the pharmaceutical composition provided by the present invention can achieve a higher therapeutic efficiency for palmoplantar keratoderma. DETAILED DESCRIPTION

[0028] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and they should also fall within the scope of the present application.

[0029] As used herein, the terms "treat" or "treatment" include reducing, alleviating, decreasing, ameliorating, alleviating or decreasing the symptoms associated with a keratotic condition in either a chronic or acute treatment setting.

[0030] As used herein, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents. When a range is used herein for a physical property, such as molecular weight, or a chemical property, such as a chemical formula, all combinations and subcombinations of that range and specific embodiments therein are intended to be included. When the term "about" refers to a numerical value or a numerical range, it means that the numerical value or numerical range referred to is an approximation within the experimental variability (or within the statistical experimental error), and thus the numerical value or numerical range may vary between 1% and 10% of the specified numerical value or numerical range.

[0031] The present invention is further described below by way of specific examples. The various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all weight contents. Unless otherwise specified, it is understood that the process is carried out at room temperature.

[0032] Embodiment 1:

[0033] In a dry environment, 12 g of zinc oxide, 0.06 g of gentamicin sulfate, 15 g of gum arabic and 15 g of modified starch are put into a grinder and ground until all of them can pass through a No. 5 sieve but cannot pass through a No. 6 sieve to obtain a mixed powder;

[0034] The mixed powder was transferred to a container, and thymol was dissolved in ethanol to obtain a thymol solution (0.6 g, 100 mL);

[0035] The thymol solution was added to the mixed powder and ground until uniform, and then water was added to the prescribed amount (1000 mL); the lotion prepared in Example 1 was obtained.

[0036] Embodiment 2:

[0037] In a dry environment, 12 g of zinc oxide, 0.06 g of gentamicin sulfate, 15 g of gum arabic and 15 g of modified starch are put into a grinder and ground until all of them can pass through a No. 5 sieve but cannot pass through a No. 6 sieve to obtain a mixed powder;

[0038] The mixed powder was transferred to a container, thymol was dissolved in ethanol, and phenol and sodium carboxymethyl cellulose were dissolved in water to obtain thymol solution (0.6 g, 100 mL), phenol solution (1.6 g, 100 mL) and sodium carboxymethyl cellulose solution (2.5 g, 300 mL);

[0039] The thymol solution, the phenol solution and glycerol (10 g) are added to the mixed powder and ground until uniform; a uniformly ground mixture is obtained, and then the sodium carboxymethyl cellulose solution is added to the uniformly ground mixture, and after sufficient mixing, water is added to the prescribed amount (1000 mL); the lotion prepared in Example 2 is obtained.

[0040] Example 3

[0041] In a dry environment, 10 g of zinc oxide, 0.05 g of gentamicin sulfate, 10 g of gum arabic and 10 g of modified starch are put into a grinder and ground until all of them can pass through a No. 5 sieve but cannot pass through a No. 6 sieve to obtain a mixed powder;

[0042] The mixed powder is transferred to a container, thymol is dissolved in ethanol, and phenol and sodium carboxymethyl cellulose are dissolved in water to obtain a thymol solution (0.5 g, 100 mL), a phenol solution (1 g, 100 mL) and a sodium carboxymethyl cellulose solution (1.5 g, 300 mL);

[0043] The thymol solution, the phenol solution and glycerol (5 g) are added to the mixed powder and ground until uniform; a uniformly ground mixture is obtained, and then the sodium carboxymethyl cellulose solution is added to the uniformly ground mixture, and after sufficient mixing, water is added to the prescribed amount (1000 mL); the lotion prepared in Example 3 is obtained.

[0044] Example 4

[0045] In a dry environment, 15 g of zinc oxide, 0.1 g of gentamicin sulfate, 20 g of gum arabic and 20 g of modified starch are put into a grinder and ground until all of them can pass through a No. 5 sieve but cannot pass through a No. 6 sieve to obtain a mixed powder;

[0046] The mixed powder is transferred to a container, thymol is dissolved in ethanol, and phenol and sodium carboxymethyl cellulose are dissolved in water to obtain a thymol solution (1 g, 100 mL), a phenol solution (3 g, 100 mL) and a sodium carboxymethyl cellulose solution (5 g, 300 mL);

[0047] The thymol solution, the phenol solution and glycerol (15 g) are added to the mixed powder and ground until uniform; a uniformly ground mixture is obtained, and then the sodium carboxymethyl cellulose solution is added to the uniformly ground mixture, and after sufficient mixing, water is added to the prescribed amount (1000 mL); the lotion prepared in Example 4 is obtained.

[0048] Comparative Example 1

[0049] In a dry environment, 5 g of zinc oxide, 0.02 g of gentamicin sulfate, 5 g of gum arabic and 5 g of modified starch are put into a grinder and ground until all of them can pass through a No. 5 sieve but cannot pass through a No. 6 sieve to obtain a mixed powder;

[0050] The mixed powder was transferred to a container, and thymol was dissolved in ethanol to obtain a thymol solution (0.3 g, 100 mL);

[0051] The thymol solution was added to the mixed powder and ground until uniform, and then water was added to the prescribed amount (1000 mL); the lotion prepared in Comparative Example 1 was obtained.

[0052] Comparative Example 2

[0053] In a dry environment, 20 g of zinc oxide, 0.15 g of gentamicin sulfate, 25 g of gum arabic and 25 g of modified starch are put into a grinder and ground until all of them can pass through a No. 5 sieve but cannot pass through a No. 6 sieve to obtain a mixed powder;

[0054] The mixed powder was transferred to a container, and thymol was dissolved in ethanol to obtain a thymol solution (1.5 g, 100 mL);

[0055] The thymol solution was added to the mixed powder and ground until uniform. After sufficient mixing, water was added to the prescribed amount (1000 mL); the lotion prepared in Comparative Example 2 was obtained.

[0056] Comparative Example 3

[0057] According to Example 1 but without adding gentamicin sulfate, the specific steps are as follows:

[0058] In a dry environment, 12.06 g of zinc oxide, 15 g of gum arabic and 15 g of modified starch were put into a grinder and ground until they could all pass through a No. 5 sieve but could not pass through a No. 6 sieve to obtain a mixed powder;

[0059] The mixed powder was transferred to a container, and thymol was dissolved in ethanol to obtain a thymol solution (0.6 g, 100 mL);

[0060] The thymol solution was added to the mixed powder and ground until uniform, and then water was added to the prescribed amount (1000 mL); the lotion prepared in Comparative Example 3 was obtained.

[0061] Comparative Example 4

[0062] The gentamicin sulfate in Example 1 was replaced with tobramycin sulfate of equal mass, and the specific steps were as follows:

[0063] In a dry environment, 12 g of zinc oxide, 0.06 g of tobramycin sulfate, 15 g of gum arabic and 15 g of modified starch are put into a grinder and ground until all of them can pass through a No. 5 sieve but cannot pass through a No. 6 sieve to obtain a mixed powder;

[0064] The mixed powder was transferred to a container, and thymol was dissolved in ethanol to obtain a thymol solution (0.6 g, 100 mL);

[0065] The thymol solution was added to the mixed powder and ground until uniform, and then water was added to the prescribed amount (1000 mL); the lotion prepared in Comparative Example 4 was obtained.

[0066] Comparative Example 5

[0067] The thymol in Example 1 was replaced with an equal mass of catechol, and the specific steps were as follows:

[0068] In a dry environment, 12 g of zinc oxide, 0.06 g of gentamicin sulfate, 15 g of gum arabic and 15 g of modified starch are put into a grinder and ground until all of them can pass through a No. 5 sieve but cannot pass through a No. 6 sieve to obtain a mixed powder;

[0069] The mixed powder was transferred to a container, and catechol was dissolved in ethanol to obtain a catechol solution (0.6 g, 100 mL);

[0070] The thymol solution was added to the mixed powder and ground until uniform, and then water was added to the prescribed amount (1000 mL); the lotion prepared in Comparative Example 5 was obtained.

[0071] Experimental Example 1: Effects of Examples and Comparative Examples on the Treatment of Palmoplantar Keratoderma

[0072] 1. Experimental animals: 60 SPF healthy male guinea pigs (5-6 weeks old, body weight 310-360 g, purchased from Jiangsu Wukong Biotechnology Co., Ltd.) were adaptively raised for 1 week at room temperature 20°C, humidity 60%, and 12 h light-dark cycle.

[0073] Before the experiment, guinea pigs were randomly divided into 12 groups, 5 in each group, and the groups were set as: normal control group, model control group, compound flumethasone ointment group, Example 1 group, Example 2 group, Example 3 group, Example 4 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, and Comparative Example 5 group.

[0074] 2. Establishment of the guinea pig dorsal ear palmoplantar keratosis animal model

[0075] Apply 5% propranolol hydrochloride emulsion evenly to the back of both ears of guinea pigs, 0.1 mL / ear, with a thickness of about 1.0 mm (1 mL = 1 cm 3 ), 10 mg / pig, twice a day for 3 weeks, to establish the guinea pig dorsal ear palmoplantar keratosis animal model.

[0076] 3. Dosage and dosage

[0077] (1) Normal control group: Apply normal saline to the back of the ear, 1 mL / ear, twice a day for 12 consecutive days.

[0078] (2) Model control group: Apply normal saline to the back of the ear, 1 mL / ear, twice a day for 12 consecutive days.

[0079] (3) Flumethasone compound ointment group: Flumethasone compound ointment was applied to the back of the ear, 0.1 mL / ear, twice a day for 12 consecutive days.

[0080] (4) Example 1 group: The lotion prepared in Example 1 was applied to the back of the ear, 1 mL / ear, and shaken well before application. The lotion was applied twice a day for 12 consecutive days.

[0081] (5) Example 2 group: The lotion prepared in Example 2 was applied to the back of the ear, 1 mL / ear, and shaken well before application. The lotion was applied twice a day for 12 consecutive days.

[0082] (6) Example 3 group: The lotion prepared in Example 3 was applied to the back of the ear, 1 mL / ear, and shaken well before application. The lotion was applied twice a day for 12 consecutive days.

[0083] (7) Group 4: The lotion prepared in Example 4 was applied to the back of the ear at a rate of 1 mL / ear. Shake well before application and apply twice a day for 12 consecutive days.

[0084] (8) Comparative Example 1: The lotion prepared in Comparative Example 1 was applied to the back of the ear, 1 mL / ear, and shaken well before application. The lotion was applied twice a day for 12 consecutive days.

[0085] (9) Comparative Example 2: The lotion prepared in Comparative Example 2 was applied to the back of the ear, 1 mL / ear, and shaken well before application. The lotion was applied twice a day for 12 consecutive days.

[0086] (10) Comparative Example 3: The lotion prepared in Comparative Example 3 was applied to the back of the ear, 1 mL / ear, and shaken well before application. The lotion was applied twice a day for 12 consecutive days.

[0087] (11) Comparative Example 4: The lotion prepared in Comparative Example 4 was applied to the back of the ear, 1 mL / ear, and shaken well before application. The lotion was applied twice a day for 12 consecutive days.

[0088] (12) Comparative Example 5: The lotion prepared in Comparative Example 5 was applied to the back of the ear at a rate of 1 mL / ear. Shake well before application and apply twice a day for 12 consecutive days.

[0089] All animals were given an equal amount of normal feed + drinking water.

[0090] 4. Test methods and indicators

[0091] 4.1. Thickness and quality detection of ear tissue

[0092] At the end of the experiment, the guinea pigs were euthanized, and the left and right ears of the guinea pigs were taken. The mass of the ear tissue was measured using an electronic balance, and the thickness of the ear tissue was measured using an electronic digital caliper.

[0093] 4.2 Baker score for ear tissue lesions

[0094] The guinea pig ears were fixed in 10% neutral formalin, embedded in paraffin, sectioned, and stained with conventional HE. Five fields of view were randomly selected to collect images under a 10 (eyepiece) × 20 (objective) field of view. The ear tissue was scored and inflammatory cells were counted according to the Baker method. The scoring criteria are shown in Table 1.

[0095] Table 1

[0096]

[0097]

[0098] 5. Test results

[0099] 5.1. Thickness and quality test results of ear tissue

[0100] Compared with the normal control group, the thickness and mass of the guinea pig ear tissue in the model control group increased, and the thickness of the left and right ears and the average ear thickness were significantly different (P < 0.05, 0.01); the mass and average mass of the left and right ears were significantly different (P < 0.05, 0.01). The above results show that the animal model of palmoplantar keratosis of the dorsum of the guinea pig ear was successfully established.

[0101] Compared with the model control group, the thickness and mass of the guinea pig ear tissue in the Example 1-4 groups were reduced, and the thickness of the left and right ears and the average ear thickness were significantly different (P < 0.05, 0.01); the mass of the left and right ears and the average mass were significantly different (P < 0.05, 0.01). The above results show that the lotions prepared in Examples 1-4 can effectively treat palmoplantar keratosis of the back of the guinea pig ear. In terms of treating palmoplantar keratosis of the back of the guinea pig ear, the lotions prepared in Examples 2 and 4 are equivalent to the compound flumethasone ointment (a common drug for treating palmoplantar keratosis). The specific results are shown in Table 2.

[0102] Table 2 Guinea pig ear tissue thickness and quality test results

[0103]

[0104]

[0105] Note: Compared with the normal control group: * P<0.05, ** P<0.01; compared with the model control group: # P<0.05, ## P<0.01.

[0106] 5.2 Baker score results of ear tissue lesions

[0107] Compared with the normal control group, the Baker score and the number of inflammatory cell infiltration in the model control group were increased, and the difference was significant (P < 0.05, 0.01). The above results showed that the animal model of guinea pig dorsal ear palmoplantar keratosis was successfully established.

[0108] Compared with the model control group, the Baker scores and the number of inflammatory cell infiltration of the guinea pigs in the Example 1-4 groups were reduced, and the difference was significant (P < 0.05, 0.01). The above results show that the lotions prepared in Examples 1-4 can effectively treat palmoplantar keratoderma of the back of the ear of guinea pigs. In terms of treating palmoplantar keratoderma of the back of the ear of guinea pigs, the lotions prepared in Examples 2 and 4 are equivalent to the compound flumethasone ointment (a common drug for treating palmoplantar keratoderma). The specific results are shown in Table 3.

[0109] Table 3 Baker score and inflammatory cell infiltration count of guinea pig ear tissue

[0110] Group Baker score Inflammatory cell infiltration Normal control group 0.94±0.48 20.7±9.00 Model control group <![CDATA[5.08±1.14 ** ]]> <![CDATA[73.4±14.47 * ]]> Compound flumethasone ointment group <![CDATA[3.75±1.28 # ]]> <![CDATA[52.7±16.74 ## ]]> Example 1 Group <![CDATA[3.90±1.31 ## ]]> <![CDATA[62.1±19.17 # ]]> Example 2 Group <![CDATA[3.67±0.79 ## ]]> <![CDATA[49.4±11.50 # ]]> Example 3 Group <![CDATA[3.86±1.58 # ]]> <![CDATA[60.7±17.58 ## ]]> Example 4 Group <![CDATA[3.78±1.02 # ]]> <![CDATA[54.6±18.42 # <!-- 8 -->]]> Comparative Example 1 <![CDATA[4.51±0.88 # ]]> <![CDATA[64.2±13.58 # ]]> Comparative Example 2 <![CDATA[4.59±0.97 ## ]]> <![CDATA[65.3±18.53 # ]]> Comparative Example 3 <![CDATA[5.02±1.25 # ]]> <![CDATA[71.2±18.53 ## ]]> Comparative Example 4 <![CDATA[5.01±0.95 # ]]> <![CDATA[70.5±13.58 # ]]> Comparative Example 5 <![CDATA[4.83±0.91 # ]]> <![CDATA[68.1±11.58 # ]]>

[0111] Note: Compared with the normal control group: * P<0.05, ** P<0.01; compared with the model control group: # P<0.05, ## P<0.01.

[0112] Experimental Example 2: Stability Test

[0113] 1. Test methods

[0114] Put the lotion (suspension) into the measuring cylinder, mix it, and measure the height of the lotion before sedimentation as H0. When the sedimentation surface no longer changes, measure the height of the sedimentation surface after sedimentation as H u Its sedimentation volume ratio F is F = (H u / H0)×100%. For a suspension, the larger the sedimentation solvent ratio, the more stable the suspension.

[0115] 2. Test results

[0116] The stability test results of Examples 1-4 and Comparative Examples 1-5 are shown in Table 4. As can be seen from Table 4, the stability of the lotions prepared in Examples 1-4 is better than that in Comparative Examples 1-5.

[0117] Table 4

[0118]

[0119]

[0120] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A pharmaceutical composition for the treatment of palmoplantar keratoderma, characterized in that: The pharmaceutical composition comprises, by weight: 10-15 parts of zinc oxide, 0.05-0.1 parts of gentamicin sulfate, 0.5-1 parts of thymol, 10-20 parts of gum arabic and 10-20 parts of modified starch.

2. The pharmaceutical composition according to claim 1, characterized in that The pharmaceutical composition further comprises, by weight: 1-3 parts of phenol, 1.5-5 parts of sodium carboxymethyl cellulose and 5-15 parts of glycerol.

3. The pharmaceutical composition according to claim 2, characterized in that The pharmaceutical composition comprises, by weight: 12-15 parts of zinc oxide, 0.06-0.1 parts of gentamicin sulfate, 0.6-1 parts of thymol, 15-20 parts of gum arabic, 15-20 parts of modified starch, 1.6-3 parts of phenol, 2.5-5 parts of sodium carboxymethyl cellulose and 10-15 parts of glycerol.

4. The pharmaceutical composition according to any one of claims 1 to 3, characterized in that The pharmaceutical composition is a cream, an ointment, a lotion, a powder, a liniment, a gel, a foam, a solution, a suspension, an emulsion, a paste or an atomized mixture.

5. The pharmaceutical composition according to claim 4, characterized in that The pharmaceutical composition is a lotion.

6. A method for preparing the pharmaceutical composition according to claim 5, wherein the pharmaceutical composition is a lotion, characterized in that: The method comprises the following steps: In a dry environment, zinc oxide, gentamicin sulfate, gum arabic and modified starch are put into a grinder and grind to obtain a mixed powder; The mixed powder is transferred to a container, and thymol, phenol and sodium carboxymethyl cellulose are dissolved in solutions respectively to obtain thymol solution, phenol solution and sodium carboxymethyl cellulose solution; The thymol solution, the phenol solution and glycerin are added to the mixed powder and ground until uniform; a uniformly ground mixture is obtained, and then the sodium carboxymethyl cellulose solution is added to the uniformly ground mixture, and after sufficient mixing, water is added to the prescribed amount; the lotion is obtained.

7. The pharmaceutical composition according to claim 1, characterized in that The palmoplantar keratoderma includes hereditary palmoplantar keratoderma and acquired palmoplantar keratoderma.

8. The pharmaceutical composition according to claim 7, characterized in that The hereditary palmoplantar keratoderma includes hereditary diffuse palmoplantar keratoderma and hereditary focal palmoplantar keratoderma.

9. The pharmaceutical composition according to claim 8, characterized in that The hereditary diffuse palmoplantar keratoses include variable erythematous keratoderma, Sybert's palmoplantar keratoderma, Olmsted syndrome and Naegeli-Franceschetti-Jadassohn syndrome.

10. The pharmaceutical composition according to any one of claims 7 to 9, characterized in that The pharmaceutical composition is applied topically to the skin on the hands and / or feet.

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