CN1103288A

CN1103288A - Local anaesthetic and its preparing method

Info

Publication number: CN1103288A
Application number: CN 93112775
Authority: CN
Inventors: 张洁
Original assignee: Individual
Current assignee: Individual
Priority date: 1993-12-02
Filing date: 1993-12-02
Publication date: 1995-06-07

Abstract

The local anesthetic belonging to percutaneous absorbent is prepared through dissolving local anesthetic (0.1-50%) in pharmaceutical acceptable solvent (0.1-75%), mixing with water to obtain suspension, and adding thickening/suspension aid (0.2-20%) with stirring, and features convenient application and quick acting. It is suitable for venipuncture and superficial operation.

Description

Local anaesthetic and its preparing method

The present invention relates to novel Transdermal absorption medicament, more particularly relate to local anesthetic cutaneous permeable agent and preparation method thereof.

As everyone knows, for such as local anaesthesia medicines such as procaine, lignocaine, traditional administrated method is broadly divided into two kinds: directly pharmaceutical aqueous solution is splashed into, is coated with or spray and water in mucomembranous surface; And inject pharmaceutical aqueous solution subcutaneous or peripheral nervous uses near doing.But because the permeability of keratodermatitis is very poor, if traditional local anaesthetics solution is coated on the skin, can not reach the effect of anesthesia skin, be used for carrying out local anesthesia and have the improper meeting of sterilizing of pain and syringe to cause the problem of infection and drug solution made by injection.

In order to overcome traditional existing deficiency of local anesthetic aqueous pharmaceutical, the U.S. has developed a kind of unguentum product (EMLA

, produce by Astra), this product comprises the mixture that the prilocaine of 2.5% lignocaine and 2.5% mixes, and forms unguentum with water.After being applied to this product on the skin, need the onset of 60～70 minutes ability, make analgesis.

An object of the present invention is to provide a kind of easy to use, rapid-action local anesthesia medicament of novelty.

A further object of the present invention provides the preparation method of described local anesthesia medicament.

The objective of the invention is to realize by following design: a kind of suspension, it comprises 0.1～50% local anesthetic, the water of 0.1～75% solvent and surplus.

Wherein said local anesthetic is that one or more are selected from the medicine in the group of being made up of lignocaine, benzocaine, tetracaine, prilocaine, procaine, butacaine, chloroprocaine, ***e, cyclomethycaine, hexylcaine hydrochloride, keracaine, ranocaine, marcaine, cincaine, clothing ferrum caine, mepivacaine, dyclonine and pramoxine, content range in suspension is 1-30%, preferably 2-10% preferably.

Described solvent is to be selected from the group of being made up of alcohols, mineral oil, vegetable oil.

Alcohols better scope of content in suspension is 0.1-50%, preferably 2-20%.Wherein said alcohols is pharmaceutically acceptable alcohol, and suitable alcohol can be, for example C ₂-C ₅Lower alkanols, polyalcohols, polyalcohols.

The better scope of the consumption of mineral oil and/or vegetable oil is 1-30%, preferably 2-20%.

A kind of local anesthetic cutaneous permeable agent, it comprises the local anesthetic of 0.1-50%, 0.1-75% solvent, the water of the pharmaceutically acceptable thickening agent of 0.1-20% and/or suspending agent and surplus.

Wherein the definition of local anesthetic, solvent and consumption are as mentioned above.

Wherein said pharmaceutically acceptable thickening agent and/or suspending agent can be, for example, such as polysorbas20, the surfactant of 40,60,80 classes or spans, cellulose family such as methylcellulose, ethyl cellulose hydroxy methocel, hydroxyethyl-cellulose hydroxypropyl cellulose etc., gel-like, such as the dextrin class of beta-schardinger dextrin-, β-hydroxypropyl cyclodextrin, and polyvidon class, polyacrylic acid or its esters or the like.

The better scope of the content of described thickening agent and/or suspending agent is 0.5-20%, and best scope is 1-10%.

As one of local anesthetic of the present invention preferable Transdermal absorption dosage form; it can also further at random comprise about 0.1-30%; be 1-15% preferably; the component of the increase cutaneous permeability of 2-10% preferably; described component is to be selected from by oleic acid and pharmaceutically acceptable salt thereof; capric acid and pharmaceutically acceptable salt thereof; cholic acid and pharmaceutically acceptable salt thereof; sodium lauryl sulphate; deoxycholic acid and pharmaceutically acceptable salt thereof; year sulphur gallbladder phenol and pharmaceutically acceptable salt thereof; deoxidation cattle sulphur gallbladder phenol and pharmaceutically acceptable salt thereof; glycocholic acid and pharmaceutically acceptable salt thereof and deoxidation sweet ammonia gallbladder phenol and pharmaceutically acceptable salt dimethyl sulfoxide, alcohols, C ₄-C ₁₄Straight chain fatty acid, C ₁₄-C ₂₀Unsaturated fatty acid, dihydroxylic alcohols, trihydroxylic alcohol, methyl laurate, glyceryl monooleate and Azone

Material in the group of being formed.

A kind of preparation method of local anesthetic cutaneous permeable agent, it comprises the following steps:

A) in the 0.1-50% local anesthetic, add pharmaceutically acceptable alcohols solvent, dissolve fully until principal agent; Its consumption ratio is a principal agent: solvent 1: 10～100: 10(weight);

B) add water to obtain suspension under the stirring, described suspension is the oil suspension of liquid state-liquid state;

This method further is also can comprise:

When c) needing, add the component of the increase cutaneous permeability of 0.1-30%, and stir.

This method can be carried out under atmosphere temperature, humidity and pressure, has been preferably preparation local anesthetic cutaneous permeable agent of the present invention in the 10-35 ℃ of temperature range.

Described in this description and percentage rate, ratio etc., unless otherwise mentioned, generally be weight percent and the heavy quantitative rate etc. of component in compositions.

To do into a detailed elaboration to the present invention by specific embodiment below.

Embodiment 1

Take by weighing 1 gram tetracaine,, make it to dissolve fully to wherein adding 2.4 gram dehydrated alcohol.Inwardly add 5.9 gram filtered water, stir fast and obtain unsettled oil suspension, add the Tween80 of 0.5 gram as suspending agent

(production of Sigma chemical company) obtains stable oil suspension after stirring fast.Adding 0.2 restrains as in the suspension in the extremely quick stirring of the polyacrylic acid of intensifier, and the continuation stirring obtained pasty masses in 30 minutes.

Embodiment 2,3 and 4

Be prepared as follows the described product of prescription with reference to embodiment 2 described technical processs.

Embodiment local anaesthetics solvent suspending agent/intensifier

21 gram lignocaine, 0.825 gram dehydrated alcohol, 0.5 gram sorbester p37,0.25 gram Plasdone

(K90)

7.3 gram water

31 gram tetracaine, 0.825 gram dehydrated alcohol, 0.5 gram polysorbate40,0.25 gram Natrasol

41 gram benzocaine, 0.825 gram isopropyl alcohol, 0.5 gram polysorbas20,0.25 gram Gelatin

7.3 gram water

Embodiment 5-10

With reference to embodiment 1 described technical process,, prepare the product of each embodiment according to following prescription.

Embodiment sequence number local anesthetic solvent suspending agent/intensifier

5 0.5 gram lignocaine, 2.7 gram dehydrated alcohol, 0.2 gram Natrasol

6.6 gram water

6 0.5 gram tetracaine, 2.7 gram butanols, 0.8 gram Klucel

6.6 gram water

7 0.5 gram benzocaine, 1 gram glycerol, 0.8 gram methylcellulose

8.3 gram water

8 0.5 gram lignocaine, 1 gram Polyethylene Glycol-4000,0.4 gram aldol sodium cellulosate

8.1 gram water

The oily glycol 0.4 gram Plasdone of 9 0.5 gram tetracaine, 1 gram

(K90)

8.1 gram water

10 0.5 gram benzocaine, 0.5 gram ethanol, 0.4 gram beta-schardinger dextrin-

8.6 gram water

Clinical trial

The product of an amount of embodiment 5 is applied on the skin, and covers last layer medical plastic adhesive plaster (Tegaderm

, 3M company product), throw off adhesive plaster after 30 minutes, put ointment on the skin with cotton ball, the skin that applied the ointment place has promptly lost the pain sensation, and its anaesthetic effect can reach 8-10 hour.

This shows that local anaesthesia Transdermal absorption medicament of the present invention is easy to use, painless, trouble and the defective of having avoided the pure injecting drug use of local fiber crops to bring; In addition, be coated with the EMLA of application with epidermisProduct is compared, and Transdermal absorption medicament of the present invention has and is easy to absorb, and is rapid-action, and the advantages such as longer duration can be advantageously used in the clinical practice of the aspects such as dept. of dermatology's operation of venipuncture and various superficial tables.

Claims

1, a kind of suspension is characterized in that it comprises the local anesthetic of 0.1～50% (weight), and the water of pharmaceutically acceptable solvent of 0.1-75% (weight) and surplus, wherein said solvent are to be selected from by alcohols, mineral oil, the group that vegetable oil is formed.

2, a kind of local anesthetic Transdermal absorption medicament, it is characterized in that it comprises 0.1-50%(weight) local anesthetic, 0.1-75%(weight) pharmaceutically acceptable solvent, 0.1-20%(weight) pharmaceutically acceptable thickening agent and/or suspending agent and water, wherein said solvent is to be selected from by pharmaceutically acceptable alcohols, mineral oil, the group that vegetable oil is formed.

3, medicament according to claim 2 is characterized in that wherein said pharmaceutically acceptable alcohols solvent is selected from C ₂-C ₅The group that lower alkanols, polyalcohols and polyalcohols are formed.

4, medicament according to claim 2 is characterized in that the numb pure medicine in wherein said part is that one or more are selected from the medicine in the group of being made up of lignocaine, benzocaine, tetracaine, prilocaine, procaine, butacaine, chloroprocaine, ***e, cyclomethycaine, hexylcaine hydrochloride, keracaine, ranocaine, marcaine, cincaine, clothing ferrum caine, mepivacaine, dyclonine and pramoxine.

5, medicament according to claim 4 is characterized in that wherein said suspending agent and/or thickening agent are to be selected from a kind of in the group that surfactant, cellulose family, gel-like, dextrin class and polyvidon and polyacrylic acid or its salt form.

6, according to claim 2 or 3 described medicaments, it is characterized in that wherein said alcohols solvent consumption is a 0.1-50%(weight).

7, medicament according to claim 6, the consumption that it is characterized in that wherein said alcohols solvent further is a 2-20%(weight).

8, medicament according to claim 2 is characterized in that it uses 1-30%(weight) mineral oil and/or vegetable oil as solvent.

9, medicament according to claim 8 is characterized in that the consumption of its mineral oil in fluid and/or vegetable oil is about 2-20%(weight).

10; medicament according to claim 2; it is characterized in that it further comprises the component of the pharmaceutically acceptable increase cutaneous permeability of 0.1-30%; wherein said component is to be selected from by oleic acid and pharmaceutically acceptable salt thereof; capric acid and pharmaceutically acceptable salt thereof; cholic acid and pharmaceutically acceptable salt thereof; sodium lauryl sulphate; deoxycholic acid and pharmaceutically acceptable salt thereof; taurocholic acid and pharmaceutically acceptable salt thereof; deoxidation taurocholic acid and pharmaceutically acceptable salt thereof; liquor-saturated its pharmaceutically acceptable salt dimethyl sulfoxide of the sweet ammonia gallbladder of glycocholic acid and pharmaceutically acceptable salt thereof and deoxidation, C ₄-C ₁₄Straight chain fatty acid, C ₁₄-C ₂₀Unsaturated fatty acid, alcohols, di-alcohols, trihydroxylic alcohol, methyl laurate, glyceryl monooleate and Azone Material in institute's composition group.

11, a kind of preparation method of local anesthetic Transdermal absorption medicament is characterized in that it comprises the following steps:

A) in the 0.1-50% local anesthetic, add pharmaceutically acceptable solvent, dissolve fully until principal agent;

B) add the water stirring and obtain suspension;

C) stir down, add pharmaceutically acceptable thickening agent of 0.2-20% and/or suspending agent again.

12, preparation method according to claim 11 is characterized in that wherein a) amount ratio of principal agent described in the step and solvent is 1: 10-100: 10(weight).

13, preparation method according to claim 11 is characterized in that wherein b) suspension of gained is the meticulous shape oil suspension of liquid-liquid state in the step.