CN116077495B - External anesthetic, preparation method thereof and auxiliary material containing same - Google Patents
External anesthetic, preparation method thereof and auxiliary material containing same Download PDFInfo
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- CN116077495B CN116077495B CN202310098574.6A CN202310098574A CN116077495B CN 116077495 B CN116077495 B CN 116077495B CN 202310098574 A CN202310098574 A CN 202310098574A CN 116077495 B CN116077495 B CN 116077495B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 20
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- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 8
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 6
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- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 claims description 3
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- 238000010171 animal model Methods 0.000 description 1
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Classifications
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
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- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
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- A—HUMAN NECESSITIES
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- A61P23/02—Local anaesthetics
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/402—Anaestetics, analgesics, e.g. lidocaine
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- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract
The invention discloses an external anesthetic and a preparation method thereof, and auxiliary materials containing the anesthetic, wherein the preparation method of the anesthetic comprises the following steps: dissolving anesthetic, adding catalyst, regulating pH to be slightly acidic, adding sulfhydrylation reagent, regulating pH, reacting, and drying. The preparation method of the external anesthetic auxiliary material comprises the following steps: preparing an external anesthetic solution; soaking the supporting layer in the solution, completely absorbing the solution, and drying the supporting layer; and (3) dissolving chitosan to prepare chitosan solution, spraying the chitosan solution onto a dried supporting layer in an electrospinning mode, forming a spinning layer on the supporting layer, then inwards folding the supporting layer, then sewing the opposite edges, and freeze-drying to obtain the chitosan. The auxiliary material contains anesthetic which is absorbed by the tissues of a patient in use, thereby achieving the purpose of stopping bleeding and relieving pain and effectively solving the problem that the existing gauze auxiliary material has no analgesic effect.
Description
Technical Field
The invention relates to the technical field of anesthetic auxiliary materials, in particular to an external anesthetic, a preparation method thereof and an auxiliary material containing the anesthetic.
Background
Anesthesia surgery is a reversible functional inhibition of the central and/or peripheral nervous system by drugs or other means, which is characterized by the loss of pain sensation as a primary sensation, to achieve painless, surgical treatment, while ensuring the life safety of perioperative patients. During the anesthesia operation, a large amount of gauze is needed for hemostasis and absorbing the flowing blood so as to ensure that the operation part is fully exposed, and medical staff can observe the wound conveniently, but due to the individual difference of patients, the sensitivity degree of the anesthesia medicine is different, and the problem that the drug effect of individual patients is lost during the operation possibly exists, so that the operation part of the patients is hard to be painful.
In daily life, the body tissues are damaged due to trauma, and the gauze is needed to stop bleeding, but the current gauze is sterile gauze, only plays a role in stopping bleeding, has no anesthesia and pain relieving effects on the trauma caused by the external trauma, and further increases the psychological burden of the patient because the patient needs to bear the pain on the body for a long time besides bearing the great psychological pressure during medical delivery. In view of the above, it is important to develop a gauze with anesthetic and analgesic effects.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides an external anesthetic, a preparation method thereof and auxiliary materials containing the anesthetic, wherein the auxiliary materials contain the anesthetic, and the anesthetic is absorbed by tissues of a patient in use, so that the purposes of stopping bleeding and relieving pain are achieved, and the problem that the existing gauze auxiliary materials have no analgesic effect is effectively solved.
In order to achieve the above purpose, the technical scheme adopted by the invention for solving the technical problems is as follows:
a preparation method of an external anesthetic comprises the following steps: dissolving the percutaneous absorption anesthetic in a solvent, adding a catalyst, regulating the pH value of the solution to be slightly acidic, then adding a sulfhydrylation reagent into the solution, continuously regulating the pH value, stirring for reaction, and drying to obtain the transdermal absorption anesthetic.
Further, the transdermally absorbable anesthetic is lidocaine, procaine, tetracaine, cocaine, or procaine.
Further, the catalyst is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride or N-hydroxysuccinimide, and the sulfhydrylation reagent is p-mercaptoaniline, thioglycollic acid, N-acetylcysteine or cysteine hydrochloride.
Further, the first time the pH is adjusted to 5.0-5.5 and the second time the pH is adjusted to 4.5-4.9.
An external anesthetic prepared by any of the above methods.
An external anesthetic comprises the above external anesthetic.
The preparation method of the external anesthetic auxiliary material comprises the following steps:
(1) Dissolving the external anesthetic to prepare an external anesthetic solution;
(2) Soaking the supporting layer in an external anesthetic solution, completely absorbing the external anesthetic solution, and then drying the supporting layer;
(3) And (3) dissolving chitosan to prepare chitosan solution, spraying the chitosan solution onto the support layer dried in the step (2) in an electrospinning mode, forming a spinning layer on the support layer, then inwards folding the support layer, and then sewing the edges, and freeze-drying to obtain the chitosan.
Further, the supporting layer is a fiber woven layer, and the pore diameter of the fiber woven layer is 16-100 meshes.
Further, the thickness of the spinning layer is 2-10mm; the porosity of the spinning layer after final drying is 30-60%.
Further, the content of the external anesthetic in the dried supporting layer in the step (2) is 0.1-0.3g/m 2 。
Further, in each of the steps (1) to (3), the operation is performed under a light-shielding condition.
The beneficial effects that the above-mentioned scheme produced are:
1. according to the invention, the thiol-modified anesthetic commonly used clinically is subjected to thiol modification, and in the use process, in the illumination environment, the thiol on the anesthetic reacts with the double bond groups on skin tissues, so that the contact permeation effect of the anesthetic on the skin is improved, the local anesthetic effect on wounds is further improved, and the pain of patients is reduced.
2. According to the invention, the sulfhydrylation modified anesthetic is dispersed on the surface of the fiber braided fabric, and the fiber braided fabric is used as an auxiliary material in the operation process, so that the anesthetic can act on a wound by the way in the operation processes of hemostasis and the like by adopting the auxiliary material, thereby realizing timely and uniform administration.
3. The inside of the fiber braided fabric is provided with the electrospinning structure, the raw material of electrospinning is chitosan, and the chitosan is spun and wrapped in the fiber braided fabric in the auxiliary material after stitching, so that the chitosan can be prevented from falling off after water absorption, and the use safety is improved; the chitosan has extremely strong water absorbability, the chitosan is deposited on the surface of the fiber fabric in an electrospinning mode and dried, the chitosan is spun to form a spongy porous structure, when the auxiliary material is used for adsorbing secretion at a wound, the porous structure can rapidly adsorb liquid at the wound, then the chitosan is spun to gradually absorb the liquid absorbed in the pores, finally, a hydrogel is formed, the hydrogel is fixed under the wrapping action of the fiber fabric, and when the auxiliary material is adsorbed to a certain extent, the auxiliary material is replaced in time; the auxiliary material prepared by the method has the effects of anesthesia and pain relief, and meanwhile, the auxiliary material has stronger water absorbability than common gauze, so that the using amount of the auxiliary material of the gauze can be reduced, the replacement frequency of doctors in the operation process can be reduced, and the using effect can be improved.
Detailed Description
The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the particular embodiments described herein are illustrative only and are not intended to limit the invention, i.e., the embodiments described are merely some, but not all, of the embodiments of the invention.
Thus, the following detailed description of the embodiments of the invention, as provided, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be made by a person skilled in the art without making any inventive effort, are intended to be within the scope of the present invention.
It is noted that relational terms such as "first" and "second", and the like, are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising one … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises an element.
The features and capabilities of the present invention are described in further detail below in connection with examples.
Example 1
An external anesthetic, the preparation method of which comprises the following steps: 1g of lidocaine is dissolved by adding ethanol, 0.1g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is added into the solution, the pH value of the solution is regulated to 5.5, then 0.2g of p-mercaptoaniline is added into the solution, the pH value is continuously regulated to 4.9, and the solution is prepared by stirring and reacting for 30min and then freeze drying.
An external anesthetic auxiliary material, the preparation method comprises the following steps:
(1) Dissolving the prepared external anesthetic in ethanol under the condition of avoiding light to prepare an external anesthetic solution;
(2) Under the condition of light shielding, the area is 1m 2 Soaking a medical cotton fiber supporting layer with the pore diameter of 20 meshes in an external anesthetic solution, completely absorbing the external anesthetic solution, and freeze-drying the supporting layer to ensure that the content of the external anesthetic in the dried supporting layer is 0.1g/m 2 ;
(3) And (3) dissolving chitosan in an acetic acid solution to prepare a chitosan solution, spraying the chitosan solution onto the dried supporting layer in the step (2) in a light-shielding condition in an electrospinning mode, forming a spinning layer on the supporting layer, then inwards folding the supporting layer, and then sewing the opposite edges, and freeze-drying to prepare the medical auxiliary material with the thickness of the spinning layer of 4mm and the porosity of 40%.
Example 2
An external anesthetic, the preparation method of which comprises the following steps: dissolving 1g of cocaine in ethanol, adding 0.1g of N-hydroxysuccinimide into the solution, regulating the pH value of the solution to be 5.1, then adding 0.2g of thioglycollic acid into the solution, continuously regulating the pH value to be 4.6, stirring the solution for 30min, and freeze-drying the solution to obtain the cocaine.
An external anesthetic auxiliary material, the preparation method comprises the following steps:
(1) Dissolving the prepared external anesthetic in ethanol under the condition of avoiding light to prepare an external anesthetic solution;
(2) Under the condition of light shielding, the area is 1m 2 Soaking cotton fiber supporting layer with aperture of 100 meshes in external anesthetic solution, completely absorbing the external anesthetic solution, and lyophilizing the supporting layer to obtain a dried supporting layer with external anesthetic content of 0.3g/m 2 ;
(3) And (3) dissolving chitosan in an acetic acid solution to prepare a chitosan solution, spraying the chitosan solution onto the dried supporting layer in the step (2) in a light-shielding condition in an electrospinning mode, forming a spinning layer on the supporting layer, then inwards folding the supporting layer, and then sewing the opposite edges, and freeze-drying to prepare the medical auxiliary material with the thickness of the spinning layer of 10mm and the porosity of 60%.
Example 3
An external anesthetic, the preparation method of which comprises the following steps: 1g procaine is dissolved by adding ethanol, 0.1g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is added into the solution, the pH value of the solution is adjusted to 5.2, then 0.2g of N-acetylcysteine is added into the solution, the pH value is continuously adjusted to 4.6, and the solution is subjected to stirring reaction for 30min and then freeze-dried, thus obtaining the procaine.
An external anesthetic auxiliary material, the preparation method comprises the following steps:
(1) Dissolving the prepared external anesthetic in ethanol under the condition of avoiding light to prepare an external anesthetic solution;
(2) Under the condition of light shielding, the area is 1m 2 Soaking cotton fiber supporting layer with aperture of 160 meshes in external anesthetic solution, completely absorbing the external anesthetic solution, and lyophilizing the supporting layer to obtain a dried supporting layer with external anesthetic content of 0.2g/m 2 ;
(3) And (3) dissolving chitosan in an acetic acid solution to prepare a chitosan solution, spraying the chitosan solution onto the dried supporting layer in the step (2) in a light-shielding condition in an electrospinning mode, forming a spinning layer on the supporting layer, then inwards folding the supporting layer, and then sewing the opposite edges, and freeze-drying to prepare the medical auxiliary material with the thickness of the spinning layer of 7mm and the porosity of 50%.
Comparative example 1
An external anesthetic, specifically lidocaine.
An external anesthetic auxiliary material, the preparation method comprises the following steps:
(1) Dissolving lidocaine in ethanol to obtain external anesthetic solution;
(2) The area is 1m 2 Soaking a medical cotton fiber supporting layer with the pore diameter of 20 meshes in an external anesthetic solution, completely absorbing the external anesthetic solution, and freeze-drying the supporting layer to ensure that the content of the external anesthetic in the dried supporting layer is 0.1g/m 2 ;
(3) Dissolving chitosan in acetic acid solution to obtain chitosan solution, spraying the chitosan solution onto the dried supporting layer in the step (2) in an electrospinning mode to form a spinning layer on the supporting layer, folding the supporting layer inwards, sewing the edges of the supporting layer after folding the supporting layer inwards, and freeze-drying to obtain the medical auxiliary material with the thickness of the spinning layer of 4mm and the porosity of 40%.
Comparative example 2
An external anesthetic, the preparation method of which comprises the following steps: 1g of lidocaine is dissolved by adding ethanol, 0.1g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is added into the solution, the pH value of the solution is regulated to 5.5, then 0.2g of p-mercaptoaniline is added into the solution, the pH value is continuously regulated to 4.9, and the solution is prepared by stirring and reacting for 30min and then freeze drying.
An external anesthetic auxiliary material, the preparation method comprises the following steps:
(1) Dissolving the prepared external anesthetic in ethanol under the condition of avoiding light to prepare an external anesthetic solution;
(2) Under the condition of light shielding, the area is 1m 2 Soaking a medical cotton fiber supporting layer with the pore diameter of 20 meshes in an external anesthetic solution, completely absorbing the external anesthetic solution, and freeze-drying the supporting layer to ensure that the content of the external anesthetic in the dried supporting layer is 0.1g/m 2 ;
(3) And (3) dissolving chitosan in an acetic acid solution to prepare a chitosan solution, spraying the chitosan solution onto the dried supporting layer in the step (2) under the light-shielding condition, forming a chitosan film layer on the supporting layer, then folding the supporting layer inwards, and then sewing the edges, and freeze-drying to prepare the medical auxiliary material with the thickness of the chitosan film layer of 4mm and the porosity of 40%.
Detailed Description
1. Analgesic Effect experiment
Experimental animals: female mice weighing 18-22g were 10
Experimental instrument equipment: multi-purpose instrument for physiology and pharmacology
Experimental medicine: anesthetic from example 1, anesthetic from comparative example 1
The experimental method comprises the following steps:
1. randomly dividing female mice into 2 groups, cutting back skin of each mouse into 5 groups, respectively cutting back skin of each mouse into a round shape with a round diameter of 1cm, respectively applying electric stimulation with the same intensity to wounds of each group of mice by using an electric needle, and measuring pain threshold of the mice by taking first voice of the mice as a response index of pain; then, the anesthetic in example 1 and the anesthetic in comparative example 1 were respectively covered on the wounds of two groups of mice for 5min, the anesthetic was removed, the same-intensity electrical stimulation was continuously applied to each group of mice wound by using an electrical needle, pain threshold values before and after the electrical stimulation of the mice were observed and recorded, and pain threshold value improvement rates of the mice were calculated, and specific results are shown in table 1.
Pain threshold increase rate = (post-dose average pain threshold-pre-dose average pain threshold)/pre-dose average pain threshold = 100%
Table 1: pain threshold statistics
From the results in the table, it can be seen that the analgesic effect of the anesthetic gauze in example 1 on the wound of the mouse is better than that of the anesthetic gauze in comparative example 1, and the difference between the two is that the anesthetic in the gauze in example 1 is subjected to sulfhydrylation modification treatment, and the treated anesthetic is easier to contact with the skin of the wound, so that the absorption of the skin of the wound on the drug is increased, and the anesthetic effect is further improved.
2. Water absorption effect experiment
Experimental medicine: water, the anesthetic from example 1 and the anesthetic from comparative example 2
The experimental method comprises the following steps: two cups of 300ml of water were taken with a measuring cup, then the gauze auxiliary materials in example 1 and comparative example 2 were simultaneously placed at the bottommost part of the measuring cup, and left stand for 20s, and at the same time, the gauze was taken out, placed above the measuring cup, the time from taking out to stopping dripping of the gauze was observed and recorded, and then the residual water amount in the measuring cup was observed and recorded, and specific results are shown in table 2.
Table 2: statistics of water absorption effect
Take out to stop dripping time(s) | Residual water (ml) | |
Example 1 (first group of mice) | 2 | 108 |
Comparative example 1 (second group of mice) | 4 | 136 |
As can be seen from the data in the above table, the auxiliary material in example 1 has a higher water absorption and water storage capacity than the auxiliary material in comparative example 1, and the main difference between the two auxiliary materials is that the chitosan in example 1 is in a spun form with a larger porosity inside, when the chitosan is put into water, the water body can rapidly enter the gap to increase the contact area between the water body and the chitosan, thereby improving the water body adsorption capacity, while the chitosan in comparative example 1 forms a compact film layer with a smaller contact area with water, so that the water absorption capacity and the water storage capacity are lower than those of the auxiliary material in example 1.
Claims (3)
1. The preparation method of the external anesthetic is characterized by comprising the following steps: dissolving the percutaneous absorption anesthetic in a solvent, adding a catalyst, adjusting the pH value of the solution to 5.0-5.5, adding a sulfhydrylation reagent into the solution, continuously adjusting the pH value to 4.5-4.9, stirring, reacting, and drying to obtain the transdermal absorption anesthetic;
wherein the percutaneous absorption anesthetic is lidocaine, procaine or cocaine; the catalyst is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride or N-hydroxysuccinimide; the sulfhydrylation reagent is p-mercaptoaniline, thioglycollic acid or N-acetylcysteine.
2. An external anesthetic, characterized in that it is prepared by the method of claim 1.
3. An external anesthetic, comprising the external anesthetic of claim 2;
the preparation method comprises the following steps:
(1) Dissolving the external anesthetic to prepare an external anesthetic solution;
(2) Soaking the supporting layer in an external anesthetic solution, completely absorbing the external anesthetic solution, and drying the supporting layer for later use;
(3) Dissolving chitosan to prepare chitosan solution, spraying the chitosan solution onto the support layer dried in the step (2) in an electrospinning mode, forming a spinning layer on the support layer, then inwards folding the support layer, and then sewing the edges, and freeze-drying to obtain the chitosan solution;
wherein the supporting layer is a fiber woven layer, and the pore diameter of the fiber woven layer is 16-100 meshes;
the thickness of the spinning layer is 2-10mm; the porosity of the spinning layer after final drying is 30-60%;
and (3) operating under the light-shielding condition in the steps (1) to (3).
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