Long-acting slow-release compound preparation for preventing and treating echinococcosis

Abstract

The invention provides a long-acting slow-release compound preparation for preventing and treating echinococcosis. The compound preparation comprises praziquantel serving as a first active ingredient and oxfendazole serving as a second active ingredient, praziquantel accounts for 5-95% of the weight of the compound preparation; the oxfendazole accounts for 5-95% of the weight of the compound preparation; the coating further comprises a biodegradable high polymer material and a dispersion medium. The biodegradable high polymer material accounts for 11.1%-14.9% of the weight of the compound preparation; and the dispersion medium accounts for 42.5%-44.4% of the weight of the compound preparation. The compound preparation has a long-acting slow-release effect, can maintain long-term prevention and control and treatment effects after being administered once, has a good treatment effect on echinococcosis prevention and control, especially adults and / or larvae of echinococcus, protects animals from being infected by pathogens in infection seasons or even longer time, controls parasitic disease transmission, and has a good application prospect in prevention and control of echinococcosis. And a transmission chain of parasites transmitted by animals is blocked.

Description

Technical Field

[0001] The invention relates to the technical field of antiparasitic drug preparations, and in particular to a compound preparation injected into an animal body for long-term prevention and treatment of echinococcosis. Background Art

[0002] Hydatid disease (echinococcosis) is a zoonosis that seriously endangers human health and the development of animal husbandry. It is listed as one of the 20 neglected tropical diseases by the WHO and is widely distributed in all continents except Antarctica.

[0003] The demand for echinococcosis prevention and control technology in the international market is considerable. According to the mathematical model of echinococcosis transmission, it is found that the control of echinococcosis transmission should start with the control of the final host. For zoonotic echinococcosis, dogs are the main final host. Different countries have explored many measures to control echinococcosis. For example, in New Zealand, severely endemic areas are given insecticides every 6 weeks, and in mildly endemic areas, they are given once every 3 months. The dose of praziquantel is 5 mg / kg each time, and the deworming coverage reaches 70%, which significantly reduces the number of new cases. Tasmania, Australia, conducts routine dog deworming tests. Cyprus stipulates that free surgery is required to remove the ovaries of female dogs, and arecoline is used for dog groups every three months. Although this program is costly, it tends to be eradicated from the endemic state. In Alaska, the United States, praziquantel (PZQ) is used to deworm dogs every month, which has led to the elimination of Echinococcus multilocularis from a highly endemic state, but when the prevention and control measures are stopped, it quickly returns to the original state. Dogs may be given praziquantel tablets or baits continuously once or twice a week for many years, but controlling the spread of tapeworm infections is very difficult. For example, it took New Zealand and Tasmania more than 30 years to eliminate parasitic infections in dogs after chemotherapy control.

[0004] Dogs are the source of infection of echinococcosis. Reducing their infection with Echinococcus can effectively prevent and control the spread of Echinococcus in epidemic areas. Therefore, the current method of "giving medication to dogs and deworming every month" is adopted. Feeding dogs with praziquantel tablets every month is one of the important measures to control echinococcosis in the entire epidemic area. However, echinococcosis is widely distributed in my country, and the number of dogs in epidemic areas is huge, making prevention and control extremely difficult. Recently, WHO recommended the development of long-acting / pulse praziquantel preparations (World Health Organization Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021-2030; World Health Organization: Geneva, 2020; ISBN 9789240010352.), as well as controlling the prevalence of echinococcosis in cattle and sheep.

[0005] There are two main types of echinococcosis in humans: cystic echinococcosis (granular echinococcosis) and alveolar echinococcosis (multilocular echinococcosis). Praziquantel has a significant effect on adult echinococcosis, but has no effect on eggs and mature cysts of echinococcosis. For sheep infected with echinococcosis, injection or oral administration of praziquantel has no therapeutic effect. The use of praziquantel alone cannot control the spread of echinococcosis (PLOS Neglected Tropical Diseases, February 2010, Volume 4, Issue 2, e616). Studies have shown that the cure rate and effectiveness of the combination of praziquantel and albendazole in the treatment of multilocular echinococcosis were 12.5% ​​and 50.0%, respectively, which is better than albendazole monotherapy (cure rate 5.0%, effectiveness 20.0%) (Observation on the effect of alternating combination of albendazole and praziquantel in the treatment of echinococcosis in Tibetan herdsmen [J]. Chinese Journal of Parasitology and Parasitic Diseases, 2021, 39(2):171-177).

[0006] Oxfendazole is a new type of highly effective, broad-spectrum, low-toxic benzimidazole carbamate drug. It has a good therapeutic effect in treating experimental alveolar coccidiosis in mice, especially in mild and moderately infected mice. It can shrink the cysts and alleviate the symptoms. The effect of treating alveolar coccidiosis in mice is significantly better than albendazole (Preliminary observation of the effect of oxfendazole in treating alveolar coccidiosis 1]. Journal of Practical Parasitology, 1999, 7(3): 116-119; Further observation of the effect of oxfendazole in treating experimental alveolar coccidiosis in mice [J]. Parasites and Infectious Diseases, 2003, 1(3): 108-112). However, oxfendazole is mainly used as a veterinary drug, and its safety for humans is still unclear.

[0007] Chinese invention patent 201710813925.1 discloses an antiparasitic drug in situ solidified sustained-release injection, and the weight-average molecular weight of the biodegradable polymer material used is 10,000-150,000. The weight-average molecular weight of the biodegradable polymer material can be selected according to different sustained-release times. When a longer sustained-release time is required for the drug, a biodegradable polymer material with a higher molecular weight tends to be selected, such as a weight-average molecular weight of 100,000-150,000; when the drug sustained-release time does not need to be very long, a biodegradable polymer material with a lower molecular weight tends to be selected, such as a weight-average molecular weight of 16,000. However, the patent only provides sustained-release effect data for a single drug component, and does not provide a compound sustained-release injection.

[0008] Chinese invention patent 202111655096.1 discloses a compound preparation with a sustained-release dosage form, which can prevent both adults and larvae of parasites at the same time, and due to the sustained-release function, this compound preparation can be administered only once, but it can be sustained-released in vitro for 1 day or several months, with the potential for long-term treatment and immunity to pathogen infection. However, the patent does not prove what unexpected technical effects can be achieved by combining the two drugs, and the sustained-release effect. The release time of the compound sustained-release preparation of oxfendazole and praziquantel provided by the patent is relatively short, and the time for releasing 90% of the drug does not exceed 2 weeks, and no selective release phenomenon has been found.

[0009] In summary, although the existing technology has means to treat echinococcosis, it lacks long-term technology to prevent echinococcosis infection and disease progression, and also lacks technology for long-term treatment of echinococcosis with a single dose. Summary of the invention

[0010] In order to overcome the defects of the above-mentioned prior art in lacking a long-term technology for preventing echinococcosis infection and disease progression, the first purpose of the present invention is to provide a compound preparation; the second purpose of the present invention is to provide a method for preparing the compound preparation; the third purpose of the present invention is to provide the use of the compound preparation in the preparation of anti-echinococcosis drugs.

[0011] The purpose of the present invention is achieved by the following technical means:

[0012] In one aspect, the present invention provides a compound preparation, comprising a first active ingredient, praziquantel, and a second active ingredient, oxfendazole;

[0013] Wherein, based on 100% of the weight of the compound preparation, the praziquantel accounts for 5% to 95% of the weight of the compound preparation; the oxfendazole accounts for 5% to 95% of the weight of the compound preparation.

[0014] In the above-mentioned compound preparation, preferably, the compound preparation further comprises a biodegradable polymer material and a dispersion medium;

[0015] The biodegradable polymer material accounts for 11.1% to 14.9% of the weight of the compound preparation; and the dispersion medium accounts for 42.5% to 44.4% of the weight of the compound preparation.

[0016] In the above-mentioned compound preparation, preferably, the biodegradable polymer material is selected from one or more combinations of polylactic acid-glycolic acid copolymer, polycaprolactone (including ester end-capping, terminal carboxyl group and terminal hydroxyl group), polytrimethylene carbonate, left-handed polylactic acid-polycaprolactone copolymer, left-handed polylactic acid, right-handed polylactic acid and racemic polylactic acid, but is not limited thereto.

[0017] In the above-mentioned compound preparation, preferably, the average molecular weight of the polylactic acid-glycolic acid copolymer is 0.8w to 16w.

[0018] In the above-mentioned compound preparation, preferably, the average molecular weight of the polycaprolactone is 0.6w to 12w.

[0019] In the above-mentioned compound preparation, preferably, the average molecular weight of the polytrimethylene carbonate is 1.0w to 19.8w.

[0020] In the above-mentioned compound preparation, preferably, the average molecular weight of the poly(L-lactic acid) is 0.6w to 12w.

[0021] In the above-mentioned compound preparation, preferably, the average molecular weight of the dextrorotatory polylactic acid is 0.8w to 17w.

[0022] In the above-mentioned compound preparation, preferably, the average molecular weight of the racemic polylactic acid is 0.5w to 16w.

[0023] In the above-mentioned compound preparation, preferably, the biodegradable polymer material is composed of a polylactic acid-glycolic acid copolymer with an average molecular weight of 0.8w to 16w and a racemic polylactic acid with an average molecular weight of 1w to 20w; and the mass ratio of the polylactic acid-glycolic acid copolymer to the racemic polylactic acid is in the range of 1:10 to 10:1.

[0024] In the above-mentioned compound preparation, preferably, the biodegradable polymer material is composed of a polylactic acid-glycolic acid copolymer with an average molecular weight of 0.8w to 16w and a polycaprolactone with an average molecular weight of 0.6w to 12w; and the mass ratio of the polylactic acid-glycolic acid copolymer to the polycaprolactone is in the range of 1:10 to 10:1.

[0025] In the above-mentioned compound preparation, preferably, the dispersion medium is selected from one or more combinations of N-methylpyrrolidone, triacetin, and benzyl benzoate, but is not limited thereto.

[0026] In the above-mentioned compound preparation, preferably, based on 100% by weight of the compound preparation, the compound preparation comprises:

[0027] The first active ingredient, praziquantel, 21.3% to 22.2%;

[0028] The second active ingredient, oxfendazole, 21.3% to 22.2%;

[0029] Biodegradable polymer materials 11.1% to 14.9%;

[0030] Dispersion medium 42.5%~44.4%.

[0031] On the other hand, the present invention also provides a method for preparing the above-mentioned compound preparation, which comprises the following steps:

[0032] The biodegradable polymer material is dissolved in a dispersant, and then the first active ingredient praziquantel and the second active ingredient oxfendazole are added and stirred evenly to obtain a compound preparation.

[0033] In another aspect, the present invention also provides use of the above-mentioned compound preparation or the compound preparation prepared by the above-mentioned method in the preparation of anti-echinococcosis drugs.

[0034] In the above use, preferably, the pathogen includes adults and / or larvae of Echinococcus.

[0035] Beneficial effects of the present invention:

[0036] The compound preparation of the present invention has a long-acting sustained-release effect. By administering the sustained-release dosage form once, a long-term prevention and control and treatment effect can be maintained. It has a good treatment effect on echinococcosis, especially adults and / or larvae of Echinococcus, and comprehensively prevents and controls the spread of echinococcosis. It can protect animals from pathogen infection during the infection season or even longer, and further control the spread of parasitic diseases and block the transmission chain of animal-transmitted parasites. After injection, it can not only cure livestock such as cattle and sheep and dogs that have been infected with echinococcosis, but also provide a relatively long-term effect of preventing re-infection. Only one administration can maintain the prevention and control effect for several months, the operation is simple, and the amount of medicine used and manpower and material resources are saved. DETAILED DESCRIPTION

[0037] In order to have a clearer understanding of the technical features, purposes and beneficial effects of the present invention, the technical scheme of the present invention is now described in detail below, but it should not be construed as limiting the scope of implementation of the present invention; the raw materials used in the following examples are all commercially available in the art unless otherwise specified; the methods used are all conventional preparation methods in the art unless otherwise specified.

[0038] Embodiments 1 to 11:

[0039] This embodiment provides a compound preparation for injection into an animal for long-term prevention and treatment of echinococcosis and a preparation method thereof. The compound preparation consists of a first active ingredient, praziquantel, a second active ingredient, oxfendazole, a biodegradable polymer material and a dispersion medium.

[0040] (1) The ingredients and formulas of the biodegradable polymer materials and dispersants of Examples 1 to 6 are shown in Table 1. The preparation method of the compound preparation of the embodiment comprises:

[0041] According to the formula in Table 1, the biodegradable polymer material was dissolved in the dispersant, and then 0.5 g of praziquantel and 0.5 g of oxfendazole were added, and the mixture was stirred well to obtain a compound preparation.

[0042] In Table 1, the average molecular weight of the polylactic acid-glycolic acid copolymer is 16w; the average molecular weight of the polylactic acid is 20w; and the average molecular weight of the polycaprolactone is 10w.

[0043] Table 1: Formula table of Examples 1 to 6

[0044]

[0045]

[0046] * Injectability refers to the ease with which a preparation passes through an injection needle. A “+” indicates that the preparation is easier to inject and a “-” indicates that the preparation is more difficult to inject.

[0047] (2) The components and formulas of the biodegradable polymer materials of Examples 7 to 11 are shown in Table 2. The preparation method of the compound preparation of the example comprises:

[0048] According to the formula in Table 2, the biodegradable polymer material was dissolved in 1.0 g of the dispersant N-methylpyrrolidone, and then 0.5 g of praziquantel and 0.5 g of oxfendazole were added, and the mixture was stirred well to obtain a compound preparation.

[0049] Table 2: Formula table of Examples 7 to 11

[0050]

[0051] Needle-pass test:

[0052] The compound preparations prepared in Examples 1 to 11 above were subjected to an acupuncture test, and the specific method was as follows:

[0053] Add the compound preparation into the syringe to simulate the actual injection process, and apply a certain force to push the solution through the syringe and needle. The greater the pushing force, the worse the needle permeability.

[0054] The experiment found that different biodegradable polymer materials and different dispersants have an effect on the viscosity (permeability) of the compound preparation. With the same dispersant, the permeability of the single-component biodegradable polymer material is relatively poor, while the permeability of the multi-component biodegradable polymer material is relatively good. With the same multi-component biodegradable polymer material, the permeability of the dispersant composed of N-methylpyrrolidone and triacetin is relatively good. The permeability of Examples 5 and 6 is the best.

[0055] Experimental Example 1: Pharmacokinetic Experiment

[0056] Six male SD rats were subcutaneously injected with the compound preparation obtained in the above Example 5 at a dose of 400 mg / kg body weight. 1 ml of blood was collected before administration (0h) and 0.08d (2h), 0.33d (8h), 1d (24h), 3d, 7d, 21d, 30d, 45d, 60d, 90d, 120d, 150d and 180d after administration, respectively, and placed in a test tube coated with heparin, centrifuged at 3500 rpm for 10 minutes, and 0.4 ml of plasma was collected and stored at -80°C for analysis. The blood drug concentrations of oxfendazole (OXF), praziquantel (PZQ), oxfendazole sulfone (OXF-SO2) and fenbendazole (FEN) in rats were determined by LC-MS. The LC-MS chromatographic conditions are as follows:

[0057] Chromatographic column: Waters XbridgeTM C18 (2.1mm×100mm, 3.5μm); column temperature: 20℃ (room temperature). Detection: ESI ion source, capillary temperature of 320℃, scanning voltage of 4.00KV, vaporization chamber temperature of 250℃, sheath gas (N2) pressure of 40Arb, auxiliary gas (N2) pressure of 8Arb, positive ion detection mode; scanning mode is selective ion monitoring (SIM) and positive ion detection mode; [MH] + quasi-molecular ion peaks m / z 316.07, 300.08, 332.07, 313.19 and 266.09 of OXF / FEN / OXS / PZQ and ALB are used as product ions for single ion monitoring for quantitative analysis. Flow rate: 0.35mL / min; injection volume: 3μL; internal standard: 200ng / mL (albendazole). The experimental results are shown in Table 3 below.

[0058] Table 3: Pharmacokinetic data of Example 5

[0059]

[0060] It can be seen from the experimental results in Table 3 that the release time of praziquantel in Example 5 in rats can reach 6 months, and the blood concentration between the 150th day and the 180th day is almost undetectable; while oxfendazole is still slowly released on the 180th day.

[0061] Oxfendazole sulfone (OXF-SO2) and fenbendazole (FEN) are both active metabolites with anti-echinococcosis activity, so the contents of these metabolites were measured simultaneously.

[0062] Experimental Example 2: Capsule Weight Inhibition Rate Experiment

[0063] Twenty mice of 6 weeks old and weighing 25-35 grams were selected and randomly divided into groups regardless of gender, with 10 mice in each group. The control group was injected with a blank preparation containing no active ingredient of the drug, and the drug-administered group was injected with the compound preparation prepared in Example 5, at 0.1 mL / mouse. After all the injections were completed, 20 mice were inoculated with 0.2 mL (about 1500 protoscoleces) of multilocular echinococcosis cyst tissue. After inoculation, they were fed normally and killed by cervical dislocation after 5 months. The abdominal cavity was opened, the multilocular echinococcosis tissue was carefully peeled off and removed, and the cyst weight of each mouse was weighed.

[0064] Efficacy calculation: Calculate the average capsule weight of the drug group and the control group, and calculate the capsule weight inhibition rate according to the following formula I. The experimental results are shown in Table 4.

[0065] Capsule weight inhibition rate = (capsule weight of control group - capsule weight of drug group) / capsule weight of control group * 100 (Formula I)

[0066] Table 4: Effect data of Example 5 on preventing infection with Echinococcus multilocularis

[0067]

[0068] Note: Negative control vs compound preparation, a(p<0.05)

[0069] Experimental Example 3: Comparative Experiment of Different Preparations

[0070] Preparation 1, blank preparation: 0.9 ml of N-methylpyrrolidone and 0.1 ml of triacetin were mixed, and 0.1 g of polylactic acid-glycolic acid copolymer and 0.24 g of polylactic acid were added and dissolved to obtain a blank preparation.

[0071] Preparation 2, compound preparation. Prepared according to the method provided in Example 5. Mix 0.9 ml of N-methylpyrrolidone and 0.1 ml of triacetin, add 0.1 g of polylactic acid-glycolic acid copolymer and 0.24 g of polylactic acid to dissolve, add 0.5 g of praziquantel and 0.5 g of oxfendazole and mix well to obtain the compound.

[0072] Preparation 3, oxfendazole subcutaneous injection: 0.9 ml of N-methylpyrrolidone and 0.1 ml of triacetin are mixed, 0.1 g of polylactic acid-glycolic acid copolymer and 0.24 g of polylactic acid are added and dissolved, and 0.5 g of oxfendazole is added and mixed to obtain the preparation.

[0073] Preparation 4, compound suspension. Grind one oxfendazole tablet (0.1 g) and one praziquantel tablet (0.1 g) into powder, add 20 ml ultrapure water and mix well, and set aside.

[0074] Preparation 5, albendazole suspension: Grind one albendazole tablet (0.2 g) into powder, add 40 ml ultrapure water and mix well, and set aside.

[0075] Experimental methods:

[0076] 60 mice of 6 weeks old and weighing 25-35 grams were selected and randomly divided into groups regardless of gender, with 10 mice in each group. Group 6 was the control group, which was not vaccinated or intervened. The rest were inoculated with 0.2 mL of multilocular echinococcosis tissue (about 1500 protoscoleces). All groups were fed normally. After 2 months, Group 1 received a subcutaneous injection of Preparation 1 (blank preparation) 0.1 mL / mouse; Group 2 received a subcutaneous injection of Preparation 2 (compound preparation) 0.09 mL / mouse; Group 3 received a subcutaneous injection of Preparation 3 (oxfendazole injection) 0.09 mL / mouse; Group 4 received oral Preparation 4 (compound suspension) 0.2 mL / mouse / day, oral administration for 4 consecutive weeks, 5 days a week; Group 5 received oral Preparation 5 (albendazole suspension) 0.2 mL / mouse / day, oral administration for 4 consecutive weeks, 5 days a week, with a cumulative dose of 4 ml / mouse. The dosing schedule is shown in Table 5.

[0077] Table 5 Intervention methods for mice infected with Echinococcus multilocularis

[0078]

[0079] The mice were fed normally for 6 months after inoculation and then autopsied. They were killed by cervical dislocation, the abdominal cavity was opened, the multilocular echinococcosis tissue was carefully peeled off and removed, and the cyst weight of each mouse was weighed.

[0080] Efficacy calculation: Calculate the average capsule weight of the drug group and the control group, and calculate the capsule weight inhibition rate according to the above formula I. Capsule weight inhibition rate = (capsule weight of the control group - capsule weight of the drug group) / capsule weight of the control group * 100 (Formula I)

[0081] The results of the comparative experiment on the therapeutic effects of different preparations are shown in Table 6.

[0082] Table 6 Comparison of therapeutic effects of different preparations

[0083]

[0084] The experimental results in Table 6 show that the compound preparation of the present invention has preventive and therapeutic effects on mice infected with Echinococcus multilocularis, and the therapeutic effect is better than that of oral albendazole preparations. In the current treatment of echinococcosis, oral albendazole marketed formulations are taken for a course of 2 weeks, repeated multiple times. However, the compound preparation of the present invention can be released for more than 6 months after a single injection.

[0085] It should be particularly pointed out that the above embodiments are only examples for clear description, and are not limitations on the implementation methods. For professionals in this field, many changes can be derived on the basis of the above description. It is not necessary and impossible to enumerate all the changes here. However, those changes that are obviously derived from them are still within the scope of protection of the present invention.

Claims

1. A compound preparation, characterized in that: The compound preparation comprises a first active ingredient, praziquantel, and a second active ingredient, oxfendazole; Wherein, based on 100% of the weight components of the compound preparation, the praziquantel accounts for 5% to 95% of the weight components of the compound preparation; the oxfendazole accounts for 5% to 95% of the weight components of the compound preparation.

2. The compound preparation according to claim 1, characterized in that: The compound preparation further comprises a biodegradable polymer material and a dispersion medium; The biodegradable polymer material accounts for 11.1% to 14.9% of the weight of the compound preparation; and the dispersion medium accounts for 42.5% to 44.4% of the weight of the compound preparation.

3. The compound preparation according to claim 2, characterized in that: The biodegradable polymer material is selected from one or more combinations of polylactic acid-co-glycolic acid, polycaprolactone (including ester end-capping, carboxyl end-capping and hydroxyl end-capping), polytrimethylene carbonate, L-polylactic acid-co-caprolactone, L-polylactic acid, D-polylactic acid and racemic polylactic acid; Preferably, the average molecular weight of the polylactic acid-glycolic acid copolymer is 0.8w to 16w; Preferably, the average molecular weight of the polycaprolactone is 0.6w to 12w; Preferably, the average molecular weight of the polytrimethylene carbonate is 1.0w to 19.8w; Preferably, the average molecular weight of the L-polylactic acid is 0.6w to 12w; Preferably, the average molecular weight of the dextrorotatory polylactic acid is 0.8w to 17w; Preferably, the average molecular weight of the racemic polylactic acid is 0.5w to 16w.

4. The compound preparation according to claim 3, characterized in that: The biodegradable polymer material is composed of a polylactic acid-glycolic acid copolymer with an average molecular weight of 0.8w-16w and a racemic polylactic acid with an average molecular weight of 1w-20w; and the mass ratio of the polylactic acid-glycolic acid copolymer to the racemic polylactic acid is in the range of 1:10-10:

1.

5. The compound preparation according to claim 3, characterized in that: The biodegradable polymer material is composed of a polylactic acid-glycolic acid copolymer with an average molecular weight of 0.8w-16w and a polycaprolactone with an average molecular weight of 0.6w-12w; and the mass ratio of the polylactic acid-glycolic acid copolymer to the polycaprolactone is in the range of 1:10-10:

1.

6. The compound preparation according to claim 2, characterized in that: The dispersion medium is selected from one or more combinations of N-methylpyrrolidone, triacetin, benzyl benzoate and pyrrolidone.

7. The compound preparation according to claim 2, characterized in that: Taking the weight components of the compound preparation as 100%, the compound preparation comprises: The first active ingredient, praziquantel, 21.3% to 22.2%; The second active ingredient, oxfendazole, 21.3% to 22.2%; Biodegradable polymer materials 11.1% to 14.9%; Dispersion medium 42.5%~44.4%.

8. A method for preparing the compound preparation according to any one of claims 1 to 7, comprising the following steps: The biodegradable polymer material is dissolved in a dispersant, and then the first active ingredient praziquantel and the second active ingredient oxfendazole are added and stirred evenly to obtain a compound preparation.

9. Use of the compound preparation according to any one of claims 1 to 7 or the compound preparation prepared by the method according to claim 8 in the preparation of anti-echinococcosis drugs.

10. The use according to claim 9, characterized in that: The hydatid cysts include adults and / or larvae of Echinococcus.

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