Application of maggot in preparation of medicine for treating psoriasis

Abstract

The invention discloses an application of maggot in preparation of a medicine for treating psoriasis, belongs to the technical field of medicines, and comprises an application of the maggot in preparation of the medicine for treating psoriasis and an application of the maggot in preparation of the medicine for treating psoriasis. The maggot is a whole worm and contains maggot active ingredients: protein, fatty acid and chitin, the mass percent of the protein in the maggot is not less than 7%, the mass percent of the fatty acid in the maggot is not less than 6%, the mass percent of the chitin in the maggot is not less than 7%, and the administration dosage of the maggot is 0.05-30mg / cm < 2 > * d when the medicine for treating the psoriasis is used; according to the application of the maggot in treating the psoriasis, compared with existing treatment medicines and methods, the maggot can achieve an unexpected curative effect, and the new application is an innovation for treating the psoriasis.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, and in particular to application of five-grain worms in preparing medicines for treating psoriasis. Background Art

[0002] Psoriasis is an immune-mediated chronic, recurrent, inflammatory, systemic disease, clinically manifested by scaly erythema or plaques, which are localized or widely distributed, with a long course and difficult to cure. The global incidence of psoriasis is 2-3%, with about 125 million patients; the number of psoriasis patients in my country is more than 7 million. Patients with neurodermatitis and eczematous dermatitis often have psoriasis-like skin lesions, such as severe itching, accompanied by papules, maculopapular rashes, blisters and other skin lesions, which can lead to skin ulceration and cause local infection, seriously affecting the patient's normal life and work.

[0003] The pathogenesis of psoriasis and psoriasis-like lesions of neurodermatitis and eczematous dermatitis is still unclear. Current studies have shown that the pathogenesis involves multiple factors such as immunity, endocrine, and genetics, among which immune system disorders are the core factor in the onset of the disease. Most patients with psoriasis and psoriasis-like lesions are mild to moderate, and topical medications are the first choice for treatment. Commonly used topical medications include glucocorticoids, vitamin D3 derivatives, retinoic acid, calcineurin inhibitors, etc., but they all have problems such as drug resistance, easy recurrence, serious adverse reactions, and many contraindications. At present, "quasi" Chinese medicines for the treatment of psoriasis and psoriasis-like lesions are extremely rare. Most of the preparations used in clinical practice are prepared by the hospital pharmacy department, and most of them are limited to use in the hospital, which is difficult to meet the treatment needs of patients. Therefore, it is urgent to develop Chinese medicine for the treatment of psoriasis.

[0004] The Chinese medicine maggot, also known as fly maggot, is the larvae or pupa shell of the common insects Lucilasericata, Chrysomyia megacephala or their closely related animals of the family Calliphoridae. The maggot was first recorded in the Compendium of Materia Medica, listed in the 40th volume of the insect section. It tastes salty and sweet, is cold in nature, and enters the spleen and stomach meridians. It has the effects of clearing heat, eliminating stagnation, and removing rickets. It can be used clinically to treat ecthyma, lip furuncle, carbuncle, ulcer, and other surgical diseases. Among them, it has a significant therapeutic effect in the treatment of ulcers with symptoms of "redness, swelling, heat, and pain". Modern research shows that the effective ingredients contained in the maggot include proteins, fatty acids, chitin, etc. (Lin Rui, Bian Haixu, Xi Miaomiao, et al., Research Progress on the Pharmacological Effects of the maggot, Chinese Pharmacy, 2017, 28(04): 558-561).

[0005] It has been reported in the literature that the five-grain worm is used to treat diseases such as anorexia, dental caries, mouth sores, and infected wounds in children. It has a high value in the treatment of chronic wounds, and it has been found to have pharmacological effects such as regulating immunity, anti-inflammatory, antibacterial, lowering blood sugar and blood lipids, anti-tumor, anti-atherosclerosis, angiogenesis, promoting wound healing, and tissue reconstruction and regeneration (Zhang Wei, Shi Xiaoli, Liu Yifan, etc., Research Progress on Active Peptide-Enzyme Chemical Components of Traditional Chinese Medicine Five-grain Worm, Shizhen Traditional Chinese Medicine, 2022, 33(08): 1978-1982). Chinese patent CN114886927A discloses the use of a five-grain worm active ingredient composition in the preparation of drugs for treating burns, diabetic ulcers, mechanical skin trauma and acne. Chinese patent CN112691123A discloses the use of a five-grain worm coating agent in the preparation of treatment of skin wound healing in diabetic rats. Chinese patent CN114796283A discloses the use of a grain worm extract in the preparation of a medicine for treating peptic ulcer, irritable bowel syndrome, bacterial enteritis and viral enteritis.

[0006] At present, there is no report on the use of Osmunda quinquefolia for treating psoriasis, neurodermatitis, eczematous dermatitis and psoriasis-like skin lesions. Therefore, the new use involved in the present invention is an innovation. Summary of the invention

[0007] In order to solve the problems of the prior art, the present invention provides the use of five grain worms in preparing a drug for treating psoriasis.

[0008] Furthermore, the grain worm is a whole worm and contains the grain worm active ingredients: protein, fatty acid, and chitin.

[0009] Furthermore, the mass percentage of protein in the grain worm is not less than 7%, the mass percentage of fatty acids is not less than 6%, and the mass percentage of chitin is not less than 7%.

[0010] Furthermore, when the drug for treating psoriasis is used, the dosage of the five grain insects is 0.05-30 mg / cm 2 *d.

[0011] Furthermore, the drug for treating psoriasis also includes a pharmaceutically acceptable carrier or excipient.

[0012] Furthermore, the carrier or auxiliary material includes a surfactant, an excipient, a stabilizer, a suspending agent, an isotonic agent, a preservative, a filler, an antioxidant, an emulsifier, a coating agent, an adhesive, a lubricant, a diluent, a solubilizer, a latent solvent, a disintegrant, a dispersant, a flavoring agent, an absorbent, a wetting agent, a buffer or a cross-linking agent.

[0013] Furthermore, the drug for treating psoriasis can be prepared into pharmaceutically acceptable dosage forms, including ointments, plasters, creams, gels, creams, pastes, liniments, paints, coatings, patches, plasters, lotions, irrigants, aerosols, sprays, powders, tablets, pills, granules, capsules, oral liquids or injections; the oral liquids are solutions, syrups, emulsions or suspensions.

[0014] Furthermore, the content of five cereal worms in every 100 grams of the dosage form is 0.01g-50g.

[0015] Beneficial effects of the present invention:

[0016] 1. The present invention uses five-grain worms to treat psoriasis, and can achieve unexpected therapeutic effects compared with existing treatment drugs and methods. This new use is an innovation in the treatment of psoriasis.

[0017] 2. The five-grain worm has a wide range of psoriasis treatments. It can be used to treat psoriasis vulgaris, articular psoriasis, erythrodermic psoriasis, pustular psoriasis, complications caused by various types of psoriasis, and psoriasis-like lesions common in neurodermatitis and eczematous dermatitis. It can also treat dermatitis, burns, diabetic ulcers, mechanical skin trauma, etc.

[0018] 3. The five-grain worm described in the present invention is a traditional natural medicine, which is recorded in "Compendium of Materia Medica", "Bencao Qiuyuan" and "Bencao Bian Du". It has low toxic and side effects on the human body, can significantly improve the patient's medication safety and medication compliance, and thus greatly improve the treatment effect and quality of life of psoriasis patients.

[0019] 4. The five-grain worm described in the present invention has a significant effect in preventing or treating psoriasis. It can significantly improve the MPASI score and tissue morphological changes of psoriasis lesions; reduce the thickness of psoriasis-like auricle swelling, the number of scratching lesions, spleen index, mast cell count and serum IL-23, IL-17A, and TNF-α levels. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a comparison diagram of skin damage of mice in different control groups at different times in the present invention;

[0021] Figure 2 It is a graph showing the MPASI score results of mice in different control groups in the present invention;

[0022] Figure 3 is a graph showing the swelling thickness of the auricles of mice in different control groups in the present invention;

[0023] Figure 4 It is the HE staining result of the back skin tissue of mice in different control groups in the present invention;

[0024] Figure 5 It is the HE staining result of the right ear skin tissue of mice in different control groups in the present invention;

[0025] Figure 6 This is a statistical result diagram of the scratching times of mice in different control groups in the present invention;

[0026] Figure 7 It is a result diagram of spleen index of mice in different control groups in the present invention;

[0027] Figure 8 This is a diagram showing the results of toluidine blue staining of the back skin tissue of mice in different control groups in the present invention;

[0028] Fig. 9 This is a result diagram of the number of mast cells in the back skin tissue of mice in different control groups in the present invention;

[0029] Fig.10 It is a result diagram of the serum "inflammatory response" related factor levels of mice in different control groups in the present invention. DETAILED DESCRIPTION

[0030] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] Example 1

[0032] The invention provides a method for preparing freeze-dried powder of five-grain worms. The method comprises: washing whole five-grain worms with 0.9% physiological saline, rinsing with distilled water after washing, pre-freezing at -30 DEG C for 2 hours, and then performing vacuum freeze drying.

[0033] Among them, the relevant parameters of vacuum freeze drying include: sublimation drying temperature -25 ° C, sublimation drying time 12h, analytical drying temperature 35 ° C, analytical drying time 10h. The method (General Principles of the 2020 Edition of the Chinese Pharmacopoeia 0832 Moisture Determination Method 2) was used for drying to determine the water content in freeze-dried grain worms, and the freeze-drying rate was calculated to be 95.0-98.5%.

[0034] It should be noted that most studies on the preparation of grain worms extract and prepare grain worms through various physical and chemical means, which destroys the protein of the grain worm body and filters the chitin of the grain worm epidermis, greatly reducing the therapeutic effect of the grain worm. The present invention, by using the whole grain worm after vacuum freeze-drying as medicine, can effectively increase the therapeutic effect of the drug.

[0035] Example 2

[0036] The present invention provides a formula of grain and insect frost, which comprises: an oil phase component and a water phase component;

[0037] The oil phase components include: 2.0g of stearic acid, 2.0g of glyceryl monoglyceride, 3.0g of cetostearyl alcohol, 0.5g of beeswax, 1.0g of vaseline, 0.5g of lanolin, 2.0g of silicone oil, 2.0g of castor oil, 2.0g of squalane, 0.5g of ethyl paraben and 3.0g of peregrin.

[0038] The aqueous phase components include: 15.0 g of glycerol, 0.01-50 g of freeze-dried corn worm powder, 0.5 g of triethanolamine, and distilled water added to 100 g.

[0039] The preparation process is as follows: the oil phase and the water phase in the prescribed amount are mixed evenly, and then heated to 85°C respectively; then the oil phase is poured into the water phase at 85°C, followed by emulsification for 8 minutes, and then stirred until condensed and allowed to stand for 24 hours to obtain the product.

[0040] Example 3

[0041] The present invention provides a pharmacodynamic study process of Osmunda quinquefolia on Imiquimod (IMQ)-induced psoriasis mice:

[0042] 1 Method

[0043] 1.1 Modeling and treatment of psoriasis mouse model

[0044] SPF male C57BL / 6 mice, 6-8 weeks old, weighing 20-25g, were selected and purchased from Chengdu Dashuo Experimental Animal Co., Ltd. The mice were housed in separate cages, the temperature was maintained at 22±2℃, the humidity was 55-75%, the light was on a 12h day and night cycle, and they were free to drink water and eat. All mice were allowed to adapt to the environment for 1 week before the experiment. Then the C57BL / 6 mice were randomly divided into a normal group, a model group, a grain worm group, and a benvimod group. On the 0th day of the experiment, the back skin of the mice was depilated. 24 hours later, vaseline cream was applied to the back skin and the inner and outer sides of the right ear auricle of the mice in the normal group, once a day, for 8 consecutive days; IMQ cream was applied to the back skin and the inner and outer sides of the right ear auricle of the mice in other groups, once a day, for 8 consecutive days. From the fourth day of the experiment, IMQ cream was applied to the back skin and the inner and outer sides of the right auricle of the mice in the five-grain insect group and the benvimod group. 4 h before and 4 h after modeling, the five-grain insect powder (0.05-30 mg / cm) was applied to the five-grain insect group. 2 *d, the benvimod group was treated with benvimod cream, 2 times / d, for 5 consecutive days.

[0045] 1.2MPASI score to detect the severity of mouse skin lesions

[0046] In the calculation of the MPASI score, because the model is a drug stimulation-induced modeling of the mouse back, the lesions are mainly limited to the back of the mouse, that is, the trunk, and the lesions of other structures are all 0. Therefore, the MPASI score of the mouse should be calculated as the product of the erythema (E, 0-4 points), infiltration (I, 0-4 points), and scaling (D, 0-4 points) of the trunk (t) and the coefficient of the total surface area occupied by the trunk (50%) and the area ratio of the accumulated lesions of the trunk (A, 0-6 points), that is, MPASI = 0.5 (Et + It + Dt) At, with a minimum of 0 points and a maximum of 36 points. The test results are as follows Figure 1-2 As shown. Figure 1 This is a comparison of mouse skin damage on day 1 and day 9;

[0047] Figure 2 This is a graph showing that Ophiopogon japonicus significantly reduced the MPASI score of psoriasis mice.

[0048] 1.3 Vernier caliper measurement of mouse ear swelling thickness

[0049] On the first and ninth days of the experiment, the thickness of the auricle of the right ear of the mouse was measured with a vernier caliper, and the average value was taken for the three measurements. The increase in the swelling thickness of the auricle (mm) = the thickness of the auricle on the ninth day (mm) - the thickness of the auricle on the first day (mm). The test results are shown in Figure 2. Figure 3 As shown. Figure 3 This is the result that the five-grain insect significantly reduced the swollen thickness of the auricle of psoriasis mice.

[0050] 1.4 HE staining to detect pathological changes in mouse tissues

[0051] The back skin tissue and right ear of mice were fixed with 4% paraformaldehyde, routinely dehydrated, paraffin-embedded, and sliced ​​at 4 μm in thickness. The slices were sealed after HE staining. The histopathological features of psoriasis were evaluated under an optical microscope, including hyperkeratosis, thinning or disappearance of the granular layer, thickening of the acanthosis, wavy epidermis extending into the dermis, and inflammatory cell infiltration. Figure 4-5 As shown. Figure 4 This is the HE result of the significant improvement of the pathological changes of the back skin tissue of psoriasis mice by O. quinquefolius (original magnification, 200×); Figure 5 This is the HE result of the significant improvement of the right ear skin tissue pathological changes in psoriasis mice by O. quinquefolius (original magnification, 200×).

[0052] 1.5 Camera video observation of mouse scratching behavior

[0053] The severity of the itching of the mice in each group was determined by observing the number of times the mice scratched within 10 minutes. The mice were placed in a transparent observation cage and adapted for 10 minutes. The scratching of the mice was recorded continuously in a quiet environment for 10 minutes, and the number of times the mice scratched was counted by replaying the video. Figure 6 As shown. Figure 6 This is the result of the grain worm significantly reducing the number of scratching times in psoriasis mice.

[0054] 1.6 Weighing and calculating the spleen index of mice

[0055] Weigh the mouse body weight (g), dissect the mouse to separate the spleen, weigh the spleen mass (mg) using an electronic balance, and calculate the spleen index. Spleen index = spleen mass (mg) / mouse body weight (g). Figure 7 As shown. Figure 7 This is the result graph showing that Ophiopogon japonicus significantly reduced the spleen index of psoriasis mice.

[0056] 1.7 Detection of mast cell numbers in mouse tissues by toluidine blue staining

[0057] The skin tissue from the back of the mouse was fixed with 4% paraformaldehyde, routinely dehydrated, paraffin-embedded, sliced ​​into 4 μm thick slices, stained with toluidine blue, and then sealed. The number of mast cells was observed and counted under an optical microscope. Figure 8-9 shown; Figure 8 This is the result of toluidine blue staining of the mouse back skin (original magnification, 200×); Fig. 9 This is the result of the grain worm significantly reducing the number of mast cells in the back skin of psoriasis mice.

[0058] 1.8ELISA method to detect the levels of "inflammatory response" related factors in mouse serum

[0059] Blood was collected from the mouse orbits and stored at -80°C. The levels of "inflammatory response" (IL-23, IL-17A, TNF-α) related factors were detected according to the instructions of the ELISA kit. Fig.10 As shown. Fig.10 Figures A to C show the results of Osmanthus fructus significantly reducing the levels of serum IL-23, IL-17A, and TNF-α in psoriasis mice.

[0060] 1.9 Results Analysis

[0061] Graphpad Prism8.0.2 software was used to perform statistical analysis on the data. The results were expressed as mean±standard deviation. One-way analysis of variance was used to compare the sample means among multiple groups, and the Sidak method was used to compare the sample means between multiple groups. P<0.05 was considered to be statistically significant.

[0062] 2 Results

[0063] 2.1 Ophiopogon japonicus significantly improved the skin pathological symptoms of psoriasis mice

[0064] In order to verify the therapeutic effect of five grain insects on psoriasis, IMQ was used to induce a psoriasis mouse model and five grain insects were given for treatment. Benvimod is a commonly used topical ointment for the topical treatment of mild to moderate stable psoriasis vulgaris in adults. Benvimod was used as a positive control for testing. The appearance of the skin on the back and left and right ears and the results of HE staining are shown in Figure 2. Figure 1-5 As shown in the figure, it can be seen that on the 9th day of the experiment, the back and right ear skin of the mice in the model group showed erythema, infiltration, and scaling, swelling of the right ear auricle, hyperkeratosis and incomplete keratinization of the stratum corneum of the back and right ear skin, thinning or disappearance of the granular layer, hypertrophy of the epidermal spinous layer, elongation and undulation of the epidermal processes, infiltration of mononuclear and multinuclear cells in the dermis, and the top of the mastoid process, etc. Psoriasis-like pathological symptoms. After treatment with five grain insects or benvimod, the MPASI score of the back skin was reduced, the swelling and thickness of the right ear auricle was reduced, and the pathological changes of the back and right ear skin tissues were significantly improved ( Figure 1-5 ). These data indicate that O. quinquefolius significantly reduces skin inflammation induced by IMQ in psoriasis mice, and has certain anti-inflammatory, wound healing, tissue reconstruction and regeneration effects.

[0065] 2.2 Grain worms significantly reduced the number of scratching times in psoriasis mice

[0066] The study found that IMQ-induced psoriasis mice showed significantly more active behaviors such as biting and licking the skin in the modeling area, and the number of scratching increased significantly. Compared with the model group, psoriasis mice treated with five grain insects or benvimod showed significantly less scratching, biting, and licking of the skin in the modeling area, and the number of scratching decreased significantly ( Figure 6 ). These data indicate that Osmanthus fructus significantly reduces the itching degree of the skin of psoriasis mice induced by IMQ and has a certain antipruritic effect.

[0067] 2.3 Ophiopogon japonicus significantly reduces the systemic immune response of psoriasis mice

[0068] The spleen is an important immune organ of the human immune system and can produce a variety of immune-active cytokines. The study found that the spleen mass of IMQ-induced psoriasis mice increased and the spleen index increased significantly. Compared with the model group, the spleen mass of psoriasis mice treated with five grain insects or benvimod decreased, and the spleen index decreased significantly ( Figure 7 ). These data indicate that O. quinquefolius significantly alleviates the systemic immune response of IMQ-induced psoriasis mice and has a certain immune regulatory effect.

[0069] 2.4 Ophiopogon japonicus significantly reduced the number of mast cells in the tissues of psoriasis mice

[0070] The study found that the number of mast cells in the back skin of IMQ-induced psoriasis mice increased significantly. Compared with the model group, the infiltration of mast cells in the back skin of psoriasis mice treated with five grain insects or benvimod was significantly improved, and the number was significantly reduced ( Figure 8-9 ). These data indicate that O. pentaphyllum significantly alleviates IMQ-induced mast cell activation in the skin tissue of psoriasis mice and has a certain inhibitory effect on mast cell activation.

[0071] 2.5 Five-grain insect significantly reduces the levels of "inflammatory response" related factors in psoriasis mice

[0072] The study found that the serum IL-23, IL-17A, and TNF-α levels of IMQ-induced psoriasis mice were significantly increased, indicating that the serum inflammatory factors were in an activated state, suggesting that the body's "inflammatory response" was more severe. Compared with the model group, the serum IL-23, IL-17A, and TNF-α levels of psoriasis mice treated with five grain insects or benvimod were significantly reduced ( Fig.10 AC). These data indicate that O. quinquefolius significantly reduces the degree of "inflammatory response" in the body of IMQ-induced psoriasis mice and has a certain anti-inflammatory effect.

[0073] comprehensive Figure 1-10 The results showed that V. pentaphyllum could significantly improve the skin damage degree of IMQ-induced psoriasis mouse model, reduce the swelling thickness of the auricle, the number of scratching times, the spleen index, the number of mast cells, and the levels of serum IL-23, IL-17A, and TNF-α in the psoriasis mouse model, thereby achieving the purpose of alleviating the skin inflammation caused by psoriasis.

[0074] in addition, Figure 1-10 Data are expressed as mean ± standard deviation (n = 6 per group). ** P<0.01, *** P < 0.001 indicates that there is a significant difference between the model group and the normal group; # P<0.05, ## P<0.01, ### P<0.001 indicates that there is a significant difference between the treatment group and the model group.

[0075] 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 principle of the present invention should be included in the protection scope of the present invention.

Claims

1. Application of Oxytricha quinata in the preparation of drugs for the treatment of psoriasis.

2. The use according to claim 1, characterized in that: The five-grain worm is a whole worm and contains the five-grain worm active ingredients: protein, fatty acid, and chitin.

3. The use according to claim 2, characterized in that: The mass percentage of protein in the grain worm is not less than 7%, the mass percentage of fatty acid is not less than 6%, and the mass percentage of chitin is not less than 7%.

4. The use according to claim 1, characterized in that: When the drug for treating psoriasis is used, the dosage of the five grain insect is 0.05-30 mg / cm 2 *d.

5. The use according to claim 1, characterized in that: The drug for treating psoriasis also includes a pharmaceutically acceptable carrier or excipient.

6. The use according to claim 5, characterized in that: The carrier or auxiliary material includes a surfactant, excipient, stabilizer, suspending agent, isotonic agent, preservative, filler, antioxidant, emulsifier, coating agent, adhesive, lubricant, diluent, solubilizer, latent solvent, disintegrant, dispersant, flavoring agent, absorbent, wetting agent, buffer or cross-linking agent.

7. The use according to claim 5, characterized in that: The drug for treating psoriasis can be prepared into pharmaceutically acceptable dosage forms, including ointments, plasters, creams, gels, creams, pastes, liniments, coatings, films, patches, plasters, lotions, rinses, aerosols, sprays, powders, tablets, pills, granules, capsules, oral liquids or injections; the oral liquids are solutions, syrups, emulsions or suspensions.

8. The use according to claim 7, characterized in that: The content of five grain worms in every 100 grams of the dosage form is 0.01g-50g.

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