Bupivacaine liposome slow-release absorbable dressing and preparation method thereof

Abstract

The bupivacaine liposome sustained-release absorbable dressing comprises an absorbable dressing body and a local anesthetic, the absorbable dressing body is used for being placed in an operation area and is a flexible and easily-shaped absorbable human body implant material, and the local anesthetic is arranged on the absorbable dressing body to form a composite wettability material. Bupivacaine lipidosome is adopted as the local anesthetic. The cobupivacaine lipidosome is arranged on the absorbable dressing to form a composite infiltrating material, and the composite infiltrating material can be used for infiltrating anesthesia of in-vivo incisions and parts with dense nerve distribution, can play an infiltrating local slow-release anesthesia effect, relieves postoperative pain and is high in safety.

Description

Technical Field

[0001] The invention relates to the technical field of medical materials, and in particular to a bupivacaine liposome sustained-release absorbable dressing and a preparation method thereof. Background Art

[0002] The problem of postoperative pain has received more and more attention in the medical community. Severe acute postoperative pain has become an important complication that affects the speed and quality of postoperative recovery and requires active prevention and treatment.

[0003] The single-shot analgesia technology currently used in clinical practice has a short analgesia duration, which can only last for a few hours and is insufficient to meet the long-term analgesia needs after surgery; continuous analgesia technologies such as the commonly used patient-controlled intravenous analgesia have weak efficacy, large dosages of opioids, and many related adverse reactions; local anesthetic continuous analgesia technology has high technical requirements, a heavy economic burden, and requires catheter infusion, which is prone to risks of leakage and infection, and is therefore limited in clinical application.

[0004] As a local anesthetic, bupivacaine has the advantages of rapid effectiveness, long duration, high safety, and strong controllability, and is widely used in clinical surgery. Bupivacaine liposomes are the first and only ultra-long-acting local anesthetic in China. It prolongs the duration of action through a unique sustained-release technology. The analgesic duration of a single injection far exceeds that of current local anesthetics. There are no other similar drugs, but there are still disadvantages such as local application in the abdominal cavity that is difficult to avoid diffusion and the location of drug onset cannot be determined. If it can be combined with an absorbable dressing, it can provide more lasting and effective analgesia without the need for additional special equipment, which makes up for the clinical demand for long-lasting, safe analgesia and simple medical operation for postoperative analgesia, providing patients with a more lasting and convenient way to relieve pain. Summary of the invention

[0005] The object of the present invention is to provide a bupivacaine liposome sustained-release absorbable dressing and a preparation method thereof for solving the above-mentioned problems.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] A bupivacaine liposome sustained-release absorbable dressing, comprising an absorbable dressing and a local anesthetic, wherein the absorbable dressing is a flexible, easily shaped absorbable human implant material, the local anesthetic is placed on the absorbable dressing to form a composite infiltrative material, the local anesthetic is bupivacaine liposome, and the DepoFoam multivesicular liposome technology is used to encapsulate bupivacaine in the multivesicular liposome, the molecular formula of the bupivacaine is C 18 H 28 N2O, the mass ratio of the bupivacaine liposome to the absorbable dressing is (2-8):100.

[0008] Preferably, the bupivacaine liposomes are composed of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin, and dierucyl phosphatidylcholine, and the mass ratio of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin, and dierucyl phosphatidylcholine is 100:35:7:15:62.

[0009] Preferably, the mass ratio of the bupivacaine liposome to the absorbable dressing is 5:100.

[0010] Preferably, the absorbable dressing comprises a supporting substrate and glycerin as a softener, and the supporting substrate is a hydrophobic biodegradable polymer.

[0011] Preferably, the supporting substrate is gauze or sponge.

[0012] The present invention also provides a method for preparing the bupivacaine liposome sustained-release absorbable dressing, which comprises the following steps:

[0013] S1, preparing a supporting substrate;

[0014] S2, weighing glycerol and distilled water in a volume ratio of 1:2, and mixing them to obtain a glycerol aqueous solution as a mixed solution A;

[0015] S3. Under vacuum conditions, immersing the support substrate in the mixed solution A, and then removing excess water by drying to obtain an absorbable dressing;

[0016] S4. Weigh 0.9% sodium chloride injection and bupivacaine liposomes successively, slowly add bupivacaine liposomes into the sodium chloride injection, gently mix evenly, and prepare mixed solution B, wherein the concentration of bupivacaine liposomes in the mixed solution B is 2 mg / ml;

[0017] S5, soaking the absorbable dressing in the mixed solution B, and then removing excess water by drying to obtain a bupivacaine liposome sustained-release absorbable dressing;

[0018] S6. Humidify the bupivacaine liposome sustained-release absorbable dressing to obtain a bupivacaine liposome sustained-release absorbable dressing with a water content of 20-30%.

[0019] After adopting the above technical solution, the present invention has the following beneficial effects compared with the background technology:

[0020] 1. The present invention constructs a composite infiltrative material by placing bupivacaine liposomes on an absorbable dressing, which can be used for infiltration anesthesia of incisions and parts with dense nerve distribution in the body. The bupivacaine liposome sustained-release absorbable dressing of the present invention is placed on a postoperative incision or a part requiring local anesthesia, which can achieve the effect of infiltration local sustained-release anesthesia and relieve postoperative pain. At the same time, the absorbable dressing of the present invention can be degraded and absorbed in the body, and has high safety.

[0021] 2. The present invention adopts a hydrophobic biodegradable polymer as a supporting substrate, adopts a glycerol aqueous solution as a solvent system, and adopts bupivacaine liposomes as a local anesthetic and is uniformly dispersed in the solvent system, similar to the principle of "applying a facial mask", which has the effect of infiltrating local anesthesia, relieves postoperative pain, and reduces the use of opioids. In addition, since different vesicles of the bupivacaine liposomes have different rupture times, bupivacaine is released from the ruptured vesicles at different times, thereby achieving the effect of extending the release time of bupivacaine.

[0022] 3. The absorbable dressing of the present invention adopts a flexible, easily shaped absorbable human implant material. On the one hand, it is easy to be inserted through the laparoscope hole during laparoscopic surgery, and on the other hand, it is easy to shape in the surgical area in the body and is not easy to cause friction pain and irritation.

[0023] 4. The absorbable dressing of the present invention is easy to cut and can be cut into a suitable size according to actual conditions. At the same time, the amount can be reduced for the elderly and children. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0025] Example 1

[0026] This embodiment discloses a bupivacaine liposome sustained-release absorbable dressing, comprising an absorbable dressing and a local anesthetic, wherein:

[0027] The absorbable dressing can be placed in the surgical area, such as the abdominal cavity, and is a flexible, easily shaped absorbable human implant material. The absorbable dressing includes a supporting substrate and glycerol as a softener, and the supporting substrate is a hydrophobic biodegradable polymer. In this embodiment, the supporting substrate is gauze.

[0028] The local anesthetic is placed on the absorbable dressing to form a composite infiltrative material. The local anesthetic is bupivacaine liposomes, which uses DepoFoam multivesicular liposome technology to encapsulate bupivacaine in multivesicular liposomes. The molecular formula of bupivacaine is C 18 H 28N2O. In this embodiment, the mass ratio of bupivacaine liposome to absorbable dressing is 2:100.

[0029] Bupivacaine liposomes are composed of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin, and dierucyl phosphatidylcholine, and the mass ratio of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin, and dierucyl phosphatidylcholine is 100:35:7:15:62.

[0030] Example 2

[0031] This embodiment discloses a bupivacaine liposome sustained-release absorbable dressing, comprising an absorbable dressing and a local anesthetic, wherein:

[0032] The absorbable dressing is a flexible, easily shaped absorbable human implant material. The absorbable dressing comprises a supporting substrate and glycerol as a softener, and the supporting substrate is a hydrophobic biodegradable polymer. In this embodiment, the supporting substrate is a sponge.

[0033] The local anesthetic is placed on the absorbable dressing to form a composite infiltrative material. The local anesthetic is bupivacaine liposomes, which uses DepoFoam multivesicular liposome technology to encapsulate bupivacaine in multivesicular liposomes. The molecular formula of bupivacaine is C 18 H 28 N2O. In this embodiment, the mass ratio of bupivacaine liposome to absorbable dressing is 8:100.

[0034] Bupivacaine liposomes are composed of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin, and dierucyl phosphatidylcholine, and the mass ratio of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin, and dierucyl phosphatidylcholine is 100:35:7:15:62.

[0035] Example 3

[0036] This embodiment discloses a bupivacaine liposome sustained-release absorbable dressing, comprising an absorbable dressing and a local anesthetic, wherein:

[0037] The absorbable dressing is a flexible, easily shaped absorbable human implant material. The absorbable dressing includes a supporting substrate and glycerol as a softener, and the supporting substrate is a hydrophobic biodegradable polymer. In this embodiment, the supporting substrate is a small part.

[0038] The local anesthetic is placed on the absorbable dressing to form a composite infiltrative material. The local anesthetic is bupivacaine liposomes, which uses DepoFoam multivesicular liposome technology to encapsulate bupivacaine in multivesicular liposomes. The molecular formula of bupivacaine is C 18 H 28N2O. In this embodiment, the mass ratio of bupivacaine liposome to absorbable dressing is 5:100.

[0039] Bupivacaine liposomes are composed of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin, and dierucyl phosphatidylcholine, and the mass ratio of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin, and dierucyl phosphatidylcholine is 100:35:7:15:62.

[0040] Example 4

[0041] This embodiment discloses a method for preparing a bupivacaine liposome sustained-release absorbable dressing, comprising the following steps:

[0042] S1, preparing a hemostatic sponge support substrate. This step is achieved by the following method:

[0043] Weigh collagen, add it into an acidic solution, stir and dissolve it, and prepare a collagen solution. The acidic solution uses a 0.6 mol / L acetic acid solution, and the concentration of the collagen solution is 15 mg / mL.

[0044] Weigh chitosan, add it into an alkaline solution, stir and dissolve it to prepare a chitosan solution. The alkaline solution uses a 0.2 mol / L NaOH solution, and the concentration of the chitosan solution is 20 mg / mL.

[0045] After the collagen solution and the chitosan solution are uniformly mixed, the pH value is adjusted to 7.5, and the solution is placed in a water bath for self-assembly into a gel, and then dialyzed for desalination and freeze-dried to obtain a hemostatic sponge. The constant temperature of the water bath is 32°C, the water bath time is 1 hour, the dialysis time is 24 hours, and the freeze-drying time is 24 hours.

[0046] S2. Weigh glycerol and distilled water in a volume ratio of 1:2, mix them to obtain a glycerol aqueous solution as mixed solution A.

[0047] S3. Under vacuum conditions, the support substrate is immersed in the mixed solution A, and then excess water is removed by drying to obtain an absorbent dressing. The vacuum pressure is 0.02 MP, the immersion time is 5 hours, the drying temperature is 35°C, and the drying time is 3 hours.

[0048] S4. Weigh 0.9% sodium chloride injection and bupivacaine liposomes in sequence, slowly add bupivacaine liposomes into the sodium chloride injection, gently mix well, and prepare mixed solution B. The concentration of bupivacaine liposomes in mixed solution B is 2 mg / ml.

[0049] S5. Soak the absorbable dressing in the mixed solution B, and then remove excess water by drying to obtain a bupivacaine liposome sustained-release absorbable dressing. The soaking time is 5 hours, the drying temperature is 30° C., and the drying time is 3 hours.

[0050] S6. Humidify the bupivacaine liposome sustained-release absorbable dressing to obtain a bupivacaine sustained-release absorbable dressing with a water content of 20%. The water vapor temperature used for humidification is 40° C. and the humidification time is 1 hour.

[0051] Example 5

[0052] This embodiment discloses a method for preparing a bupivacaine liposome sustained-release absorbable dressing, comprising the following steps:

[0053] S1, preparing a hemostatic gauze support substrate. This step is achieved by the following method:

[0054] Hydroxyethyl cellulose and polyvinyl alcohol are dissolved in deionized water, stirred and swelled at 20°C, and then heated to 70-90°C and stirred for 1 hour to obtain a cellulose solution. The weight ratio of hydroxyethyl cellulose to polyvinyl alcohol is 1:1.5.

[0055] Dissolve carboxymethyl chitosan and hyaluronic acid in deionized water and stir for 1 hour to obtain a chitosan solution. The weight ratio of carboxymethyl chitosan to hyaluronic acid is 1:1.5.

[0056] Dissolve genipin in deionized water to obtain a crosslinking agent solution.

[0057] The chitosan solution and the cellulose solution are mixed to form a mixed solution, which is stirred for 1 hour. The cross-linking agent solution is added dropwise to the mixed solution while stirring, and then ultrasonically vibrated to obtain a spinning solution.

[0058] The spinning solution is subjected to electrostatic spinning to obtain hemostatic gauze.

[0059] S2. Weigh glycerol and distilled water in a volume ratio of 1:2, mix them to obtain a glycerol aqueous solution as mixed solution A.

[0060] S3. Under vacuum conditions, the support substrate is immersed in the mixed solution A, and then excess water is removed by drying to obtain an absorbent dressing. The vacuum pressure is 0.02MP, the immersion time is 5 hours, the drying temperature is 35°C, and the drying time is 6 hours.

[0061] S4. Weigh 0.9% sodium chloride injection and bupivacaine liposomes in sequence, slowly add bupivacaine liposomes into the sodium chloride injection, gently mix well, and prepare mixed solution B. The concentration of bupivacaine liposomes in mixed solution B is 2 mg / ml.

[0062] S5. Soak the absorbable dressing in the mixed solution B, and then remove excess water by drying to obtain a bupivacaine liposome sustained-release absorbable dressing. The soaking time is 5 hours, the drying temperature is 35° C., and the drying time is 5 hours.

[0063] S6. Humidifying the bupivacaine sustained-release absorbable dressing to obtain a bupivacaine liposome sustained-release absorbable dressing with a water content of 30%. The humidification uses a water vapor temperature of 40° C. for 0.5 hours.

[0064] The present invention adopts a hydrophobic biodegradable polymer as a supporting substrate, adopts a glycerol aqueous solution as a solvent system, adopts bupivacaine as a local anesthetic and is uniformly dispersed in the solvent system, similar to the principle of "applying a facial mask", and has the effect of infiltration local anesthesia, relieves postoperative pain, and reduces the use of opioid drugs. The bupivacaine sustained-release absorbable dressing of the present invention is used for postoperative pain relief, and can be used for infiltration anesthesia for incisions and parts with dense nerve distribution in the body.

[0065] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A bupivacaine liposome sustained-release absorbable dressing, characterized in that: The invention comprises an absorbable dressing and a local anesthetic, wherein the absorbable dressing is a flexible, easily shaped absorbable human implant material, the local anesthetic is placed on the absorbable dressing to form a composite infiltrative material, the local anesthetic is bupivacaine liposome, and the DepoFoam multivesicular liposome technology is used to encapsulate bupivacaine in the multivesicular liposome, and the molecular formula of the bupivacaine is C 18 H 28 N2O, the mass ratio of the bupivacaine liposome to the absorbable dressing is (2-8):

100.

2. The bupivacaine liposome sustained-release absorbable dressing according to claim 1, characterized in that: The bupivacaine liposome is composed of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin and dierucyl phosphatidylcholine, and the mass ratio of bupivacaine, cholesterol, 1,2-palmitoyl phosphatidylglycerol, tricaprylin and dierucyl phosphatidylcholine is 100:35:7:15:

62.

3. The bupivacaine liposome sustained-release absorbable dressing according to claim 2, characterized in that: The mass ratio of the bupivacaine liposome to the absorbable dressing is 5:

100.

4. The bupivacaine liposome sustained-release absorbable dressing according to any one of claims 1 to 3, characterized in that: The absorbable dressing comprises a supporting substrate and glycerin as a softener, wherein the supporting substrate adopts a hydrophobic biodegradable polymer.

5. The bupivacaine liposome sustained-release absorbable dressing according to claim 4, characterized in that: The supporting substrate is gauze or sponge.

6. A method for preparing the bupivacaine liposome sustained-release absorbable dressing according to claim 5, characterized in that: The following steps are involved: S1, preparing a supporting substrate; S2, weighing glycerol and distilled water in a volume ratio of 1:2, and mixing them to obtain a glycerol aqueous solution as a mixed solution A; S3. Under vacuum conditions, immersing the support substrate in the mixed solution A, and then removing excess water by drying to obtain an absorbable dressing; S4. Weigh 0.9% sodium chloride injection and bupivacaine liposomes successively, slowly add bupivacaine liposomes into the sodium chloride injection, gently mix evenly, and prepare mixed solution B, wherein the concentration of bupivacaine liposomes in the mixed solution B is 2 mg / ml; S5, soaking the absorbable dressing in the mixed solution B, and then removing excess water by drying to obtain a bupivacaine liposome sustained-release absorbable dressing; S6. Humidify the bupivacaine liposome sustained-release absorbable dressing to obtain a bupivacaine liposome sustained-release absorbable dressing with a water content of 20-30%.