CN111388744B

CN111388744B - Gel storage, preparation method thereof and application of gel storage in preparation of postoperative hemostatic preparation

Info

Publication number: CN111388744B
Application number: CN202010043831.2A
Authority: CN
Inventors: 罗亮; 黄丽萍; 张一漪; 孟凡玲
Original assignee: Huazhong University of Science and Technology
Current assignee: Huazhong University of Science and Technology
Priority date: 2020-01-15
Filing date: 2020-01-15
Publication date: 2021-05-18
Anticipated expiration: 2040-01-15
Also published as: CN111388744A

Abstract

The invention relates to a gel storage, a preparation method thereof and application of the gel storage in preparation of a postoperative hemostatic preparation, and belongs to the technical field of biological medicines. The gel storage comprises 40-55 parts by mass of phospholipid, 40-55 parts by mass of glyceride and 5-20 parts by mass of cosolvent; or the outer layer gel reservoir is wrapped outside the inner layer gel reservoir; the outer layer gel storage comprises 28-38 parts by mass of phospholipid, 62-70 parts by mass of glyceride and 1-8 parts by mass of cosolvent, and the inner layer gel storage comprises 40-55 parts by mass of phospholipid, 40-55 parts by mass of glyceride and 5-20 parts by mass of cosolvent. Preferably, the gel reservoir further comprises a drug. The invention uses two raw materials of phospholipid and glyceride, and the gel precursor can be quickly gelatinized by meeting water through mixing, thereby quickly sealing bleeding points. The inner layer gel of the double-layer storage has the characteristics of quick gelation and high strength, the bleeding point is quickly sealed, the outer layer gel has strong adhesion, and the whole gel system is ensured not to easily fall off.

Description

Gel storage, preparation method thereof and application of gel storage in preparation of postoperative hemostatic preparation

Technical Field

The invention belongs to the technical field of biological medicines, and particularly relates to a gel storage, a preparation method thereof and application of the gel storage in preparation of a postoperative hemostatic preparation.

Background

Bleeding is one of the most common manifestations after trauma occurs, but uncontrolled bleeding is considered to be a significant cause of death for the patient. The traditional hemostatic materials mainly comprise gauze, bandages, tourniquets and the like. However, conventional hemostasis is at the expense of blood supply to the distal tissue and is prone to complications.

Later, many new hemostatic materials have been developed, such as zeolites, sponges, polymeric materials, inorganic materials, nanomaterials, and the like. They each have a number of drawbacks. For example, zeolite materials generate heat during hemostasis, which may cause body damage. Inorganic materials are not metabolized well in the body, and the like.

Meanwhile, in many cases, the hemostatic material is required to have the property of rapid hemostasis without causing excessive blood loss. The gauze super-hydrophilic material can effectively stop bleeding, but often causes excessive blood loss. Many gel materials can directly seal the wound surface by utilizing the adhesive force of the materials, and are potential hemostatic materials. However, many gel materials are difficult to synthesize, have weak adhesion and are easy to fall off. Therefore, there is an urgent need to develop a good gel material suitable for hemostasis.

Disclosure of Invention

The invention solves the technical problems that the existing gel hemostatic material can not realize rapid hemostasis and has weak adhesion force to cause easy falling off, and provides a gel storage, which comprises 40-55 parts by mass of phospholipid, 40-55 parts by mass of glyceride and 5-20 parts by mass of cosolvent. The invention uses two raw materials of phospholipid and glyceride, and the gel precursor can be quickly gelatinized by meeting water through mixing, thereby quickly sealing bleeding points.

According to a first aspect of the present invention, there is provided a gel depot comprising 40 to 55 parts by mass of a phospholipid, 40 to 55 parts by mass of a glyceride and 5 to 20 parts by mass of a cosolvent.

Preferably, the gel reservoir further comprises a drug;

preferably, the drug is a hemostatic agent, an anti-inflammatory agent, or an analgesic.

Preferably, the phospholipid is soybean lecithin or egg yolk lecithin; the glyceride is diglyceride, triolein or cholesylglyceride; the cosolvent is absolute ethyl alcohol, methanol, propylene glycol or polyethylene glycol.

According to another aspect of the present invention, there is provided a gel reservoir comprising an outer layer of gel reservoir and an inner layer of gel reservoir, the outer layer of gel reservoir being wrapped around the outer portion of the inner layer of gel reservoir; the outer layer gel storage reservoir comprises 28-38 parts by mass of phospholipid, 62-70 parts by mass of glyceride and 1-8 parts by mass of cosolvent, and the inner layer gel storage reservoir comprises 40-55 parts by mass of phospholipid, 40-55 parts by mass of glyceride and 5-20 parts by mass of cosolvent.

Preferably, the outer layer gel reservoir and/or the inner layer gel reservoir further comprises a drug;

According to another aspect of the present invention, there is provided a method of preparing a gel reservoir as described in any one of the above, comprising the steps of:

(1) mixing 40-55 parts by mass of phospholipid, 40-55 parts by mass of glyceride and 5-20 parts by mass of cosolvent to obtain a gel precursor;

(2) and (2) filling the gel precursor obtained in the step (1) into a syringe, and then pushing the gel precursor, wherein the gel precursor is gelatinized in water to obtain the gel storage.

Preferably, after the phospholipid, the glyceride and the cosolvent are mixed, the method further comprises the step of adding a medicament;

According to another aspect of the present invention, there is provided a method of preparing a gel reservoir as described herein, comprising the steps of:

(1) mixing 28-38 parts by mass of phospholipid and 62-70 parts by mass of glyceride, adding 1-8 parts by mass of cosolvent to obtain an outer-layer gel precursor, adding 40-55 parts by mass of phospholipid and 40-55 parts by mass of glyceride, and adding 5-20 parts by mass of cosolvent to obtain an inner-layer gel precursor;

(2) respectively filling the outer-layer gel precursor and the inner-layer gel precursor obtained in the step (1) into a syringe of a double-syringe, then pushing the inner-layer gel precursor, gelling the inner-layer gel precursor with water to form inner-layer gel, and then pushing the outer-layer gel precursor to form outer-layer gel outside the inner-layer gel, thus obtaining the gel storage.

Preferably, in the preparation process of the outer layer gel precursor and/or the inner layer gel precursor, after the cosolvent is added, the method further comprises the step of adding a medicament;

According to a further aspect of the present invention there is provided the use of any one of the gel depots for the preparation of a post-operative haemostatic preparation.

Generally, compared with the prior art, the above technical solution conceived by the present invention mainly has the following technical advantages:

(1) the invention uses two raw materials of phospholipid and glyceride, and the gel precursor can be quickly gelatinized by meeting water through mixing, thereby quickly sealing bleeding points.

(2) The gel depot of the present invention achieves rapid hemostasis without excessive blood loss, without sacrificing blood supply to the distal tissue, and without causing complications. The hemostatic process can not generate heat, can not cause the injury of the organism, and can be well metabolized and removed in vivo.

(3) According to the invention, preferably, the phospholipid and glyceride gel precursors with different proportions are prepared into double-layer gel for postoperative hemostasis; the gel precursor preparation with different properties adopts a double-barrel syringe to obtain the effect of a double-layer gel drug storage by injection, and the preparation can be quickly gelated when meeting water to play a role in stopping bleeding. The inner layer gel has the characteristics of quick gelation and high strength, can quickly seal bleeding points, has strong adhesion of the outer layer gel, and ensures that the whole gel system is not easy to fall off.

(4) The gel storage preferably also comprises medicines which can be hemostatic medicines, anti-inflammatory medicines or analgesics, can be used together with the hemostatic medicines to achieve a better hemostatic effect, can also be used together with the analgesics to relieve the pain of a patient through slow release medicines, and can be used together with the anti-inflammatory medicines to prevent inflammation and promote wound healing.

Drawings

FIG. 1 is a diagram of a single layer gel of the present invention.

FIG. 2 is a diagram of a bilayer gel of the present invention.

FIG. 3 illustrates the in vitro hemostasis process of the present invention.

FIG. 4 illustrates the in vivo hemostasis process of the present invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

Example 1

A gel storage used for hemostasis after operation is prepared from the following raw materials in percentage by weight: 50 parts by mass of soybean lecithin, 50 parts by mass of glycerol dioleate and 10 parts by mass of absolute ethyl alcohol, and the mark is LG 50/50.

The preparation steps are as follows:

s1: uniformly mixing 50 parts by mass of phospholipid, 50 parts by mass of glyceride and 10 parts by mass of cosolvent on a mixer to completely dissolve the phospholipid and the glyceride to obtain a gel precursor;

s2: the gel precursor obtained in step S1 is loaded into a syringe barrel of an injector, and then the gel precursor is pushed into water, and the gel precursor is gelled with water to form a gel, i.e., the gel storage is obtained, as shown in fig. 1.

Example 2

A gel storage used for hemostasis after operation is prepared from the following raw materials in percentage by weight: 40 parts by mass of soybean lecithin, 40 parts by mass of glycerol dioleate and 5 parts by mass of absolute ethyl alcohol, and the mark is LG 40/40.

The preparation steps are as follows:

s1: uniformly mixing 40 parts by mass of phospholipid, 40 parts by mass of glyceride and 5 parts by mass of cosolvent on a mixer to completely dissolve the phospholipid and the glyceride to obtain a gel precursor;

s2: and (4) loading the gel precursor obtained in the step (S1) into a syringe barrel of an injector, and then pushing the gel precursor into water, wherein the gel precursor is gelatinized with water to form gel, namely the gel storage is obtained.

Example 3

A gel storage used for hemostasis after operation is prepared from the following raw materials in percentage by weight: 55 parts by mass of soybean lecithin, 55 parts by mass of glycerol dioleate and 20 parts by mass of absolute ethyl alcohol, and the mark is LG 55/55.

The preparation steps are as follows:

s1: uniformly mixing 55 parts by mass of phospholipid, 55 parts by mass of glyceride and 20 parts by mass of cosolvent on a mixer to completely dissolve the phospholipid and the glyceride to obtain a gel precursor;

Example 4

A gel reservoir comprising an outer layer of gel reservoir and an inner layer of gel reservoir, the outer layer of gel reservoir being wrapped around the outer portion of the inner layer of gel reservoir; the outer layer gel storage reservoir comprises 35 parts by mass of phospholipid, 65 parts by mass of glyceride and 5 parts by mass of cosolvent, and the inner layer gel storage reservoir comprises 45 parts by mass of phospholipid, 45 parts by mass of glyceride and 10 parts by mass of cosolvent.

The preparation steps are as follows:

s1: mixing 35 parts by mass of phospholipid and 65 parts by mass of glyceride, adding 5 parts by mass of cosolvent to obtain an outer-layer gel precursor, and adding 45 parts by mass of phospholipid and 45 parts by mass of glyceride to 10 parts by mass of cosolvent to obtain an inner-layer gel precursor;

s2: respectively filling the outer layer gel precursor and the inner layer gel precursor obtained in the step (1) into a syringe barrel of a double-barrel syringe, then pushing the inner layer gel precursor into water, gelling the inner layer gel precursor with water to form inner layer gel, and then pushing the outer layer gel precursor to form outer layer gel outside the inner layer gel, namely obtaining the gel storage, as shown in fig. 2.

Example 5

A gel reservoir comprising an outer layer of gel reservoir and an inner layer of gel reservoir, the outer layer of gel reservoir being wrapped around the outer portion of the inner layer of gel reservoir; the outer layer gel storage comprises 28 parts by mass of phospholipid, 64 parts by mass of glyceride and 8 parts by mass of cosolvent, and the inner layer gel storage comprises 40 parts by mass of phospholipid, 55 parts by mass of glyceride and 5 parts by mass of cosolvent.

The preparation steps are as follows:

s1: mixing 28 parts by mass of phospholipid and 64 parts by mass of glyceride, adding 8 parts by mass of cosolvent to obtain an outer-layer gel precursor, and adding 40 parts by mass of phospholipid and 55 parts by mass of glyceride to 5 parts by mass of cosolvent to obtain an inner-layer gel precursor;

s2: respectively filling the outer-layer gel precursor and the inner-layer gel precursor obtained in the step (1) into a syringe barrel of a double-barrel syringe, then pushing the inner-layer gel precursor into water, gelling the inner-layer gel precursor with water to form inner-layer gel, and then pushing the outer-layer gel precursor to form outer-layer gel outside the inner-layer gel, thus obtaining the gel storage.

Example 6

A gel reservoir comprising an outer layer of gel reservoir and an inner layer of gel reservoir, the outer layer of gel reservoir being wrapped around the outer portion of the inner layer of gel reservoir; the outer layer gel storage reservoir comprises 37 parts by mass of phospholipid, 62 parts by mass of glyceride and 1 part by mass of cosolvent, and the inner layer gel storage reservoir comprises 52 parts by mass of phospholipid, 40 parts by mass of glyceride and 8 parts by mass of cosolvent.

The preparation steps are as follows:

s1: mixing 37 parts by mass of phospholipid and 62 parts by mass of glyceride, adding 1 part by mass of cosolvent to obtain an outer-layer gel precursor, and adding 52 parts by mass of phospholipid and 40 parts by mass of glyceride to 8 parts by mass of cosolvent to obtain an inner-layer gel precursor;

Example 7

Fresh animal blood (10-15 IU corresponding to 1 ml) containing 1% heparin sodium is taken for 100ul each and added into 12 penicillin bottles respectively. The control group was not treated at all. LG35 group 300ul of LG of 35/65 was added. LG 50 group 300ul of LG of 50/50 was added. The LG35+ LG 50 group was added to 150ul of each LG precursor. One of the vials in each group was turned upside down for 30s,2min,5min, respectively, and a photograph was taken. It can be seen that most of the blood in LG 50 can be stopped at 30s, approximately half of the blood volume is also stopped by LG35+ LG 50, and LG35 also has a certain hemostatic effect. At 2min, LG 50 and LG35+ LG 50 can substantially completely stop blood, and LG35 stops most of blood. The three gels can stop bleeding completely within 5min, and have high blood coagulation degree and no easy falling off. As shown in fig. 3.

Example 8

Normal mice were anesthetized to maintain vital signs. A part of the liver was removed and a bleeding point was made with a sharp instrument. The mouse liver bleeds to a certain extent after 1min, and the gel of LG 50/50 is injected by using a double-barrel syringe at the moment, so that the bleeding point is quickly closed by using the characteristics of quick gelation and high strength of the gel in the proportion. Then, the gel of LG 35/65 is injected immediately to further close the bleeding point, and the gel adhesion is strong in the proportion, so that the whole gel system is not easy to fall off. The bleeding status of the mice was observed within the next 30s-4min, and the mice essentially no longer bleed. Then, 4 minutes after injecting the gel, the gel was removed and the wound was seen to have completely stopped bleeding. As shown in fig. 4.

It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and that any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.

Claims

1. A gel reservoir comprising an outer layer of gel reservoir and an inner layer of gel reservoir, the outer layer of gel reservoir being wrapped around the outer portion of the inner layer of gel reservoir; the outer layer gel storage reservoir comprises 28-38 parts by mass of phospholipid, 62-70 parts by mass of glyceride and 1-8 parts by mass of cosolvent, and the inner layer gel storage reservoir comprises 40-55 parts by mass of phospholipid, 40-55 parts by mass of glyceride and 5-20 parts by mass of cosolvent.

2. A gel reservoir according to claim 1, wherein the outer layer and/or inner layer further comprises a drug.

3. A gel depot according to claim 2, wherein the drug is a hemostatic agent, an anti-inflammatory agent or an analgesic.

4. A method of preparing a gel reservoir according to any of claims 1 to 3, comprising the steps of:

5. The method for preparing a gel depot according to claim 4, wherein the step of adding a drug is further included after adding a cosolvent in the process of preparing the outer layer gel precursor and/or the inner layer gel precursor.

6. A method of preparing a gel depot according to claim 5, wherein the drug is a hemostatic, anti-inflammatory or analgesic.

7. Use of a gel depot according to any one of claims 1-3 for the preparation of a postoperative haemostatic preparation.