Saramectin ointment pharmaceutical composition and preparation method thereof

Abstract

The invention belongs to the technical field of veterinary drug preparations, and particularly relates to a selamectin ointment pharmaceutical composition and a preparation method thereof, and the selamectin ointment pharmaceutical composition comprises the following components by mass: 2%-20% of selamectin, 2%-12% of dipropylene glycol monomethyl ether, 10%-50% of isopropanol, 10%-50% of polyethylene glycol 400, 10%-50% of polyethylene glycol 3350, 5%-15% of caprylic / capric polyethylene glycol glyceride, 5%-15% of sodium dodecyl benzene sulfonate, 5%-10% of sodium dodecyl benzene sulfonate, and the balance of water. The cleaning agent comprises the following components in percentage by weight: 1%-8% of oleyl alcohol, 0.5%-5% of dimeticone, 0.01%-0.1% of butylated hydroxytoluene and 1%-5% of cassava starch polymethylsesquioxane The preparation method comprises the following steps: dissolving the Sarah rhzomorph in the dipropylene glycol monomethyl ether, the isopropanol and the butylated hydroxytoluene, then mixing with the matrix (the polyethylene glycol 400 and the polyethylene glycol 3350 are heated and uniformly mixed in advance), the emulsifier and other components, and homogenizing to obtain the Sarah rhzomorph emulsion. The prepared selamectin ointment is good in transdermal effect, accurate administration of animal auricles can be achieved, and animal medication compliance is improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of veterinary pharmaceutical preparations, and particularly relates to a transdermal ointment composition based on selamectin and its preparation process. In particular, the present invention provides a selamectin ointment preparation comprising a specific penetration enhancer, a solvent and an ointment base ratio, which is suitable for the prevention and treatment of internal and external parasite infections in animals dogs and cats, and particularly relates to a selamectin ointment pharmaceutical composition and its preparation method. Background Art

[0002] Avermectin compounds are a group of macrolide anti-parasitic drugs produced by the fermentation of Streptomyces, which are produced by the fermentation metabolism of the genus Streptomyces spp. Through its unique mechanism of action of irreversibly activating glutamate-gated chloride channels, leading to neuromuscular paralysis of parasites, it has established an excellent anthelmintic spectrum in the field of veterinary medicine. Selamectin (SEI) is an avermectin antibiotic fermented from a new strain of genetically recombinant Streptomyces avermitilis, which is used as an anti-animal internal and external parasite drug, showing good liposolubility and tissue permeability.

[0003] Existing clinical data show that the killing efficiency of selamectin against common external parasites in dogs and cats (including Ctenocephalides felis, Ctenocephalides canis, Demodex canis, etc.) and internal parasites (such as Toxocara canis, Ancylostoma caninum) can reach over 98.7% (based on the pharmacodynamics report of FDANADA 141-051). Its unique long-acting protection property (the effective blood drug concentration can be maintained for 28-35 days after administration) makes it widely used in the prevention of canine heartworm disease (Dirofilaria immitis). In addition, the good safety of selamectin makes it irreplaceable in clinical young dogs and cats.

[0004] Current veterinary anti-parasitic preparations mainly cover the following dosage form systems: 1) Pour-on formulations, which have problems with dosage deviation caused by drug migration; 2) Sprays, which are limited by environmental temperature sensitivity and the risk of pulmonary inhalation; 3) Shampoos, which have low bioavailability due to insufficient contact time; 4) Injectables, which may cause adverse reactions at the injection site. Compared with traditional topical drops, using an ointment dosage form for precise administration at the edge of the auricle can not only ensure sufficient drug absorption but also provide compliance for animal administration; and a pre-filled glass syringe with precise graduations is used as the device, and the precise control of the administration volume is achieved through the visual graduations; it is particularly suitable for pets with dynamic body weight changes during the growth and development stage, as well as breeders who need to manage multiple pets with different body weights at the same time. A single preparation can meet the individualized administration needs of multiple pets with different body weights and growth stages. Summary of the Invention

[0005] In view of the technical defects of the existing selamectin drops: (1) The strong volatility of the solvent system leads to the loss of active ingredients; (2) The liquid dosage form is prone to leakage and contamination; (3) The degree of specification standardization is insufficient, and multiple vials / multiple specifications need to be used in combination for pets with special body weights, etc. This invention innovatively develops a new type of ointment preparation and its preparation process. Through the improvement of the dosage form and the integration of the administration device, the following are achieved: (1) Improving the compliance of animal administration; (2) Avoiding the attenuation of drug efficacy caused by solvent volatilization; (3) Eliminating the risk of liquid leakage; (4) A single vial has a wider body weight coverage range, suitable for precise administration of dogs and cats with different body weights; (5) The ointment preparation is more convenient to use on the auricle and has a good anti-parasitic effect; (6) It is more convenient for commercial mass production.

[0006] In this invention, isopropyl alcohol and oleyl alcohol are used as transdermal penetration enhancers. The combined transdermal absorption enhancer in the ointment can synergistically enhance the transdermal penetration ability of the active ingredient, significantly improve the skin penetration efficiency of selamectin, and thus strengthen the systemic anti-parasitic effect of the preparation. The core advantage of this invention is that, compared with the traditional topical drops for administration to the skin of the animal's neck, using an ointment dosage form for precise administration at the edge of the auricle can not only ensure sufficient drug absorption but also provide compliance for animal administration; and a pre-filled glass syringe with precise graduations is used as the device, and the precise control of the administration volume is achieved through the visual graduations; it is particularly suitable for pets with dynamic body weight changes during the growth and development stage, as well as breeders who need to manage multiple pets with different body weights at the same time. A single preparation can meet the individualized administration needs of multiple pets with different body weights and growth stages.

[0007] The object of this invention is achieved through the following technologies:

[0008] A selamectin ointment, every 100 g of this ointment contains: 2 - 20 g of selamectin, 2 - 12 g of dipropylene glycol methyl ether, 10 - 50 g of isopropanol, 10 - 50 g of polyethylene glycol 400, 10 - 50 g of polyethylene glycol 3350, 5 - 15 g of polyethylene glycol glycerol caprylate / caprate, 1 - 8 g of oleyl alcohol, 0.5 - 5 g of dimethicone, 0.01 - 0.1 g of dibutylhydroxytoluene, 1 - 5 g of tapioca starch polymethylsilsesquioxane.

[0009] The preparation method of the above-mentioned selamectin ointment is as follows:

[0010] (1) Weigh isopropanol, dipropylene glycol methyl ether, and dibutylhydroxytoluene, and mix them evenly; add selamectin and stir until completely dissolved to obtain Phase A;

[0011] (2) Heat polyethylene glycol 400 and polyethylene glycol 3350 to 70 °C, mix them evenly, and then cool to 40 °C to obtain Phase B;

[0012] (3) Weigh polyethylene glycol glycerol caprylate / caprate, oleyl alcohol, dimethicone, and tapioca starch polymethylsilsesquioxane, and stir and mix them evenly to obtain Phase C;

[0013] (4) Add Phase A and Phase C to Phase B, and stir and homogenize to form a uniform and delicate ointment.

[0014] The advantages and unique effects of the present invention are as follows:

[0015] The present invention has ingeniously selected selamectin and several excipients to form a combination that can be transdermally absorbed to achieve the effect of internal and external deworming. Moreover, a prefilled glass syringe with precise graduations is used as the device, and the precise control of the administration volume is achieved through the visualizable graduations; it is especially suitable for pets with dynamic body weight changes during the growth and development stage, as well as breeders who need to manage multiple pets with different body weights at the same time. A single preparation can meet the personalized administration needs of multiple pets with different body weights and growth stages.

[0016] The following examples are provided to more comprehensively and detailedly illustrate the present invention, but the examples do not limit the present invention, which is completely limited by the appended claims. Specific implementation plan

[0017] The method of the present invention will be further described in detail below with specific examples.

[0018] Examples 1 - 4:

[0019] Examples 1 - 4 all prepared the selamectin ointment of the present invention. The prescription amounts of the raw and auxiliary materials in every 100 g of the selamectin ointment in each example are shown in Table 1 below.

[0020] Table 1 Dosages of raw and auxiliary materials in Examples 1 - 4 (100 g)

[0021]

[0022] The method steps for preparing selamectin ointment from the above raw and auxiliary materials are as follows:

[0023] (1) Weigh isopropyl alcohol, dipropylene glycol methyl ether, and dibutylhydroxytoluene, and mix them evenly; add selamectin and stir until completely dissolved to obtain Phase A;

[0024] (2) Heat polyethylene glycol 400 and polyethylene glycol 3350 to 70 °C, mix them evenly, and then cool to 40 °C to obtain Phase B;

[0025] (3) Weigh caprylic / capric polyethylene glycol glyceride, oleyl alcohol, dimethicone, and tapioca starch polymethylsilsesquioxane, and stir and mix them evenly to obtain Phase C;

[0026] (4) Add Phase A and Phase C to Phase B, and stir and homogenize to form a uniform and delicate ointment.

[0027] Table 2 Detection results of the products prepared in each example

[0028]

[0029] The selamectin ointments prepared in the above Examples 1 to 4 are all white ointments. After 3 months of investigation under the accelerated test conditions (40 ± 2 °C, RH 65 ± 5%), the content of selamectin is stable and the properties have no significant changes.

[0030] Test Examples 1-4, anti-parasite test

[0031] 1. Test samples: Prepare samples according to Examples 1-4;

[0032] 2. Test method: Select 60 cats from a dog and cat farm, clean the cat's body surface to kill the surface parasites. Divide the cats evenly into 6 groups, with 10 cats in each group. Group I is the group of Example 1, Group II is the group of Example 2, Group III is the group of Example 3, Group IV is the group of Example 4, Group V is the positive control group, and Group VI is the negative control group. Weigh each cat in each group, and introduce about 100 cat lice to the front chest of each cat. After 2 days of introduction, apply selamectin ointment to the earlobe. Do not massage the application site and do not use it on damaged skin. The dosage per 1 kg of body weight is 0.05 g. Each cat in Group I uses the sample of Example 1, each cat in Group II uses the sample of Example 2, each cat in Group III uses the sample of Example 3, each cat in Group IV uses the sample of Example 4, each cat in Group V uses the commercially available control sample, and each cat in Group VI uses the placebo blank excipient. Respectively, count the number of dead cat lice of each group of cats at 24 and 48 h after administration. At each time point, select 4 cats from each group to calculate the mortality rate;

[0033] 3. Experimental results

[0034]

[0035]

[0036] As can be seen from the data in Table 4, the effect of the selamectin ointment prepared in Examples 1-4 of the present invention in killing parasites is remarkable. The mortality rate reaches over 95% at 24 hours, and even reaches 100% at 48 hours. Among them, the 24-hour and 48-hour mortality rates of the parasites of the selamectin ointment prepared in Example 2 are the highest, which is the best example of the present invention. For the compound preparation in the negative control group, since it lacks selamectin, the mortality rates at 24 hours and 48 hours are both 0.

[0037] The selamectin ointment described in the present invention has good stability, is convenient to use, and the dosage is accurate and easy to control. The usage method is: administer 0.05 g per kilogram of body weight to dogs and cats once a month, and apply it to the inner edge of the auricle that is not easily licked. It can be used for the prevention and treatment of internal and external parasites in dogs and cats.

[0038] The above embodiments only illustratively explain the principles and effects of the present invention, and do not limit the present invention. Any person familiar with this technology in the art shall not modify the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes completed by those with ordinary knowledge in the technical field without departing from the technical idea provided by the present invention are still covered by the claims of the present invention.

Claims

1. A selamectin-containing ointment, characterized in that, The external ointment described above contains selamectin, a compound penetration enhancer, a solvent, an ointment base, a stabilizer, an antifoaming agent, an ointment shaping regulator, etc. The weight percentages of each component in the selamectin ointment are as follows: selamectin 2% - 20%, penetration enhancer 11% - 58%, solvent 12% - 67%, ointment base 20% - 70%, stabilizer (butylated hydroxytoluene) 0.01% - 0.1%, antifoaming agent (dimethyl silicone oil) 0.5% - 5%, ointment shaping regulator (cassava starch polymethylsilsesquioxane) 1% - 5%.

2. The selamectin ointment according to claim 1, wherein, The penetration enhancer described above is a composition of one or more of isopropanol, oleyl alcohol, diethylene glycol monoethyl ether, polyethylene glycol glycerol caprylate / caprate, glycerol monolinoleate, polyglycerol fatty acid ester, propylene glycol laurate, oleoyl polyoxyethylene glycerol ester, polyoxyethylene stearate.

3. The selamectin ointment according to claim 1, characterized in that, The compound penetration enhancer described above is a composition of isopropanol and oleyl alcohol, and the penetration enhancer accounts for 11% - 58% of the weight of the selamectin ointment.

4. The selamectin ointment according to claim 1, characterized in that, The solvent described above is a mixed solution of dipropylene glycol methyl ether and isopropanol, and the solvent accounts for 12% - 67% of the weight of the selamectin ointment.

5. The selamectin ointment according to claim 1, wherein The ointment base described above is polyethylene glycol 400 and polyethylene glycol 3350, and the ointment base accounts for 20% - 70% of the weight of the selamectin ointment.

6. The preparation method of the selamectin ointment according to claim 1, characterized in that, It includes the following steps: (1) Weigh isopropanol, dipropylene glycol methyl ether, and butylated hydroxytoluene, and mix them evenly; add selamectin and stir until completely dissolved to obtain Phase A; (2) Heat polyethylene glycol 400 and polyethylene glycol 3350 to 70°C, mix them evenly, and cool to 40°C to obtain Phase B; (3) Weigh polyethylene glycol glycerol caprylate / caprate, oleyl alcohol, dimethyl silicone oil, and cassava starch polymethylsilsesquioxane, and stir and mix them evenly to obtain Phase C; (4) Add Phase A and Phase C to Phase B, and stir and homogenize to form a uniform and delicate ointment.

7. Use of the selamectin ointment according to any one of claims 1 - 5 in the preparation of a drug for inhibiting and killing parasites in and on animals, and the administration method is precise administration at the edge of the animal's auricle.

8. The application according to claim 7, wherein The parasites described above are fleas, lice, mites, roundworms, hookworms, or heartworms.

9. The application according to claims 7-8, characterized in that, The animals described above are dogs and cats.

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