CN103860454A - Epsiprantel transdermal preparation and use thereof - Google Patents

Abstract

The invention belongs to the technical field of veterinary drugs and discloses an epsiprantel transdermal preparation. The psiprantel transdermal preparation contains 8-35wt% of epsiprantel, 40-60wt% of a 206 adjuvant and 5-45wt% of an aqueous solution or purified water. The invention also discloses a use of the epsiprantel transdermal preparation. The epsiprantel transdermal preparation can be used conveniently. Compared with the oral preparation, the epsiprantel transdermal preparation has the same effects of treating and preventing schistosomiasis transmission.

Description

Epsiprantel preparation capable of permeating skin and application thereof

Technical field

The present invention relates to the epsiprantel medicine of prevention and cure of schistosomiasis, relate in particular to a kind of epsiprantel preparation capable of permeating skin and application thereof.

Background technology

Schistosomiasis endemic is in 76 countries and regions such as Perenniporia martius, be a kind of serious infecting both domestic animals and human parasitic disease that endangers, be worldwide distribution, global compromised population is up to 600,000,000 people, number of the infected reaches 200,000,000 people, and the whole world has at least more than 20,000 people to die from schistosomicide every year.Before the clinical practice of thoroughly go out on a large scale spiral shell and blood fluke vaccine realizes, Studies On Antibilharzial Drugs is still the Main Means of prevention and cure of schistosomiasis.The medicine that is used for the treatment of at present schistosomicide mainly contains praziquantel, epsiprantel, artemisinine and derivant as punt-pole methyl ether etc.In these medicines, epsiprantel is high with its curative effect, short treating period, untoward reaction are few, can single-dose treatment, and the advantage such as easy to use, is recommended as the choice drug for the treatment of schistosomicide by WHO.Present stage, epsiprantel preparation for animals is still tablet and powder, exists absorption difference, cause the shortcomings such as the low and side effect of utilization ratio of drug is large, and because most domestic animals are ruminant, oral epsiprantel easily destroys the balance of stomach bacterium colony.Although occurred that at present good absorbing, the epsiprantel injection that utilization ratio of drug is high, epsiprantel injection still exist administration inconvenience, easily bring the shortcomings such as pain to domestic animal.

Summary of the invention

The technical problem to be solved in the present invention is to provide a kind of epsiprantel preparation capable of permeating skin, not only convenient drug administration of this preparation capable of permeating skin, and have the same treatment of oral formulations and blocking-up schistosomiasis propagation effect.

In addition, also need to provide a kind of application of above-mentioned epsiprantel preparation capable of permeating skin.

In order to solve the problems of the technologies described above, the present invention is achieved through the following technical solutions:

In one aspect of the invention, provide a kind of epsiprantel preparation capable of permeating skin, comprised epsiprantel, 206 adjuvants and aqueous solution or pure water, its percentage by weight is: epsiprantel 8%-35 %, 206 adjuvant 40%-60%, aqueous solution or pure water 5%-45%.

Preferably, the percentage by weight of described epsiprantel is 20%-30%, because the epsiprantel preparation capable of permeating skin therapeutic effect of 20%-30% concentration is good.Preferred, the percentage by weight of described epsiprantel is 24%.

Preferably, the percentage by weight of described 206 adjuvants is 50%, i.e. 206 adjuvants/(epsiprantel+aqueous solution or pure water)=50/50 (weight ratio), in the epsiprantel preparation capable of permeating skin good stability of this ratio preparation.

The administration time of described epsiprantel preparation capable of permeating skin is any one day that infects after schistosomicide.Preferably, the administration time of described epsiprantel preparation capable of permeating skin is the 28th day or any a day after 28 days of infecting after schistosomicide, because within the 28th day or 28 days, use epsiprantel preparation capable of permeating skin, successful and stable later.

Preferably, after infection schistosomicide, during 2-25 days, use epsiprantel preparation capable of permeating skin, transdermal 2-3 time, effect is relatively good.

Preferably, for the bilharzial ill domestic animal of subinfection or people again, the administration time of epsiprantel preparation capable of permeating skin is the 2-25 days again infecting after schistosomicide, and early treatment is effective.

Preferably, described epsiprantel preparation capable of permeating skin also comprises the transdermal penetrating agent that percentage by weight is 0.1-5%, and this transdermal penetrating agent is selected from the poly-different glycol glyceride of sub-oleoyl, isopropyl myristate, azone, propylene glycol, N-methyl-the adjoin a kind of or two or more combination arbitrarily in pyrrolidone, oleic acid or Oleum menthae.In epsiprantel preparation capable of permeating skin, add the transdermal penetrating agent with transdermal enhancing effect, can guarantee that ingredient is easy to transdermal, thereby improve the bioavailability of pharmaceutical preparation.

In another aspect of this invention, also provide the preparation method of above-mentioned epsiprantel preparation capable of permeating skin, comprised the following steps:

Appropriate 206 adjuvants, aqueous solution or pure water are heated to 28 ℃-32 ℃ respectively;

206 adjuvants of preheating and epsiprantel are mixed, and add aqueous solution or the further mix homogeneously of pure water of preheating, until obtain epsiprantel preparation capable of permeating skin.

In another aspect of this invention, also provide the application of above-mentioned epsiprantel preparation capable of permeating skin in the medicine of preparation treatment schistosomicide.

In the present invention, term " 206 adjuvant " refers to the adjuvant of Montanide ISA 206 series of match Bick (SEPPIC) company of France production, comprise Montanide ISA 206, ISA 206VG etc., this adjuvant belongs to oil emulsion adjuvant, is W/O/W type (w/o/w) immunological adjuvant of a class containing octadecanoid acid and anhydrous Nitranitol.Before 206 adjuvants, all in vaccine, use as immunological adjuvant, in order to strengthen the specific immune response of body to antigen vaccine, and 206 adjuvants in epsiprantel preparation capable of permeating skin of the present invention are to use as a kind of medicine solvent, can make the fat-soluble medicines such as epsiprantel reach higher solubility, have no side effect again, can also give full play to drug effect simultaneously.

Epsiprantel preparation capable of permeating skin of the present invention, not only convenient drug administration, and evident in efficacy in prevention and cure of schistosomiasis, safely, have no side effect.

The specific embodiment

The invention provides a kind of epsiprantel preparation capable of permeating skin, comprise epsiprantel, 206 adjuvants and aqueous solution or pure water, its percentage by weight is: epsiprantel 8%-35 %, 206 adjuvant 40%-60%, aqueous solution or pure water 5%-45%.

Preferably, the percentage by weight of epsiprantel is 20%-30%, and experiment confirms that the epsiprantel preparation capable of permeating skin therapeutic effect of 20%-30% concentration is good.Preferred, the percentage by weight of epsiprantel is 24%.

Preferably, the percentage by weight of 206 adjuvants is 50%, i.e. 206 adjuvants/(epsiprantel+aqueous solution or pure water)=50/50 (weight ratio), in the epsiprantel preparation capable of permeating skin good stability of this ratio preparation.

The administration time of epsiprantel preparation capable of permeating skin is any one day that infects after schistosomicide.Preferably, the administration time of epsiprantel preparation capable of permeating skin is the 28th day or any a day after 28 days of infecting after schistosomicide, because within the 28th day or 28 days, use epsiprantel preparation capable of permeating skin, successful and stable later.

Preferably, epsiprantel preparation capable of permeating skin also comprises the transdermal penetrating agent that percentage by weight is 0.1-5%, and this transdermal penetrating agent is selected from a kind of or two or more combination arbitrarily in the poly-different glycol glyceride of sub-oleoyl, isopropyl myristate, azone, propylene glycol, N-methyl-ketopyrrolidine, oleic acid or Oleum menthae.In epsiprantel preparation capable of permeating skin, add the transdermal penetrating agent with transdermal enhancing effect, can guarantee that ingredient is easy to transdermal, thereby improve the bioavailability of pharmaceutical preparation.

The preparation method of epsiprantel preparation capable of permeating skin of the present invention, comprises the following steps:

Appropriate 206 adjuvants, aqueous solution or pure water are heated to 28 ℃-32 ℃ respectively;

206 adjuvants of preheating and epsiprantel are mixed, and add aqueous solution or the further mix homogeneously of pure water of preheating, until obtain epsiprantel preparation capable of permeating skin.

Be described in further detail below by embodiment.

embodiment 1

(1) measure 206 adjuvants of 54m1; Sterilizing PBS (PH8.0) 38.32m1 of configuration; Above-mentioned solvent is heated to 30 ℃ ± 2 ℃;

(2) take 7. 68g epsipranteies, pour in aseptic beaker, be preheating to 30 ℃ ± 2 ℃;

(3) 54m1 preheating 206 adjuvants that measure are added in beaker;

(4) rotary head of FJ-200 high speed dispersion homogenizer is placed in the beaker that epsiprantel and 206 adjuvants are housed;

(5) low speed (200-300 rev/min) starts stir and the 38.32m1PBS of preheating is added gradually, and the flow velocity of PBS is at 5-10 liter/min;

(6) accelerate to 2000 revs/min and keep 10 minutes;

(7) stop stirring the epsiprantel preparation capable of permeating skin making containing 8% (percentage by weight) epsiprantel, wherein the percentage by weight of 206 adjuvants is 50%, percent by volume is 54%; Then the emulsion making is placed in to low temperature (4 ℃-12 ℃).

embodiment 2

(1) measure 206 adjuvants of 43.2m1; The sterile saline 33.6m1 of configuration; Above-mentioned solvent is heated to 30 ℃ ± 2 ℃;

(2) take 23. 2g epsipranteies, pour in aseptic beaker, be preheating to 30 ℃ ± 2 ℃

(3) 43.2m1 preheating 206 adjuvants that measure are added in beaker;

(4) rotary head of FJ-200 high speed dispersion homogenizer is placed in the beaker that epsiprantel and 206 adjuvants are housed;

(5) low speed (200-300 rev/min) starts stir and the 33.6m1 normal saline of preheating is added gradually, and the flow velocity of normal saline is at 5-10 liter/min;

(6) accelerate to 2000 revs/min and keep 10 minutes;

(7) stop stirring the epsiprantel preparation capable of permeating skin making containing 24% (percentage by weight) epsiprantel, wherein the percentage by weight of 206 adjuvants is 40%, percent by volume is 43.2%; Then the emulsion making is placed in to low temperature (4 ℃-12 ℃).

embodiment 3

(1) measure 206 adjuvants of 64.8m1; Measure sterile purified water 5.2m1; Above-mentioned solvent is heated to 30 ℃ ± 2 ℃;

(2) take 30g epsiprantel, pour in aseptic beaker, be preheating to 30 ℃ ± 2 ℃;

(3) 64.8m1 preheating 206 adjuvants that measure are added in beaker;

(4) rotary head of FJ-200 high speed dispersion homogenizer is placed in the beaker that epsiprantel and 206 adjuvants are housed;

(5) low speed (200-300 rev/min) starts stir and the 5.2m1 pure water of preheating is added gradually, and the flow velocity of pure water is at 5-10 liter/min;

(6) accelerate to 2000 revs/min and keep 10 minutes;

(7) stop stirring the epsiprantel preparation capable of permeating skin making containing 31.5% (percentage by weight) epsiprantel, wherein the percentage by weight of 206 adjuvants is 60%, percent by volume is 64.8%; Then the emulsion making is placed in to low temperature (4 ℃-12 ℃).

embodiment 4

(1) measure 206 adjuvants of 43.2m1; Sterilizing PBS (PH8.0) 22.92m1 of configuration; Above-mentioned solvent is heated to 30 ℃ ± 2 ℃;

(2) take 33.88g epsiprantel, pour in aseptic beaker, be preheating to 30 ℃ ± 2 ℃;

(3) 43.2m1 preheating 206 adjuvants that measure are added in beaker;

(4) rotary head of FJ-200 high speed dispersion homogenizer is placed in the beaker that epsiprantel and 206 adjuvants are housed;

(5) low speed (200-300 rev/min) starts stir and the 22.92m1PBS of preheating is added gradually, and the flow velocity of PBS is at 5-10 liter/min;

(6) accelerate to 2000 revs/min and keep 10 minutes;

(7) stop stirring the epsiprantel preparation capable of permeating skin making containing 35% (percentage by weight) epsiprantel, wherein the percentage by weight of 206 adjuvants is 40%, percent by volume is 43.2%; Then the emulsion making is placed in to low temperature (4 ℃-12 ℃).

Claims (9)

1. an epsiprantel preparation capable of permeating skin, is characterized in that, comprises epsiprantel, 206 adjuvants and aqueous solution or pure water, and its percentage by weight is: epsiprantel 8%-35%, 206 adjuvant 40%-60%, aqueous solution or pure water 5%-45%.

2. epsiprantel preparation capable of permeating skin according to claim 1, is characterized in that, the percentage by weight of described epsiprantel is 20%-30%.

3. epsiprantel preparation capable of permeating skin according to claim 2, is characterized in that, the percentage by weight of described epsiprantel is 24%.

4. according to the epsiprantel preparation capable of permeating skin described in any one in claims 1 to 3, it is characterized in that, the percentage by weight of described 206 adjuvants is 50%.

5. according to the epsiprantel preparation capable of permeating skin described in any one in claims 1 to 3, it is characterized in that, the administration time of described epsiprantel preparation capable of permeating skin is any one day that infects after schistosomicide.

6.. epsiprantel preparation capable of permeating skin according to claim 5, is characterized in that, the administration time of described epsiprantel preparation capable of permeating skin is the 28th day or any a day after 28 days of infecting after schistosomicide.

7. epsiprantel preparation capable of permeating skin according to claim 1, it is characterized in that, also comprising percentage by weight is the transdermal penetrating agent of 0.1-5%, and this transdermal penetrating agent is selected from a kind of or two or more combination arbitrarily in the poly-different glycol glyceride of sub-oleoyl, isopropyl myristate, azone, propylene glycol, N-methyl-ketopyrrolidine, oleic acid or Oleum menthae.

8. the preparation method of epsiprantel preparation capable of permeating skin described in claim 1, is characterized in that, comprises the following steps:

Appropriate 206 adjuvants, aqueous solution or pure water are heated to 28 ℃-32 ℃ respectively;

206 adjuvants of preheating and epsiprantel are mixed, and add aqueous solution or the further mix homogeneously of pure water of preheating, until obtain epsiprantel preparation capable of permeating skin.

9.. the application of epsiprantel preparation capable of permeating skin in the medicine of preparation treatment schistosomicide described in claim 1.