CN109200331B

CN109200331B - Lung sealing medical gel and preparation method and application thereof

Info

Publication number: CN109200331B
Application number: CN201811086696.9A
Authority: CN
Inventors: 汪伟; 李丹; 李绿巍; 何铭峰; 俞益雷; 朱家喜; 许利利; 朱明华
Original assignee: Hangzhou Yahui Biotechnology Co ltd
Current assignee: Hangzhou Yahui Biotechnology Co ltd
Priority date: 2015-12-17
Filing date: 2015-12-17
Publication date: 2021-06-25
Anticipated expiration: 2035-12-17
Also published as: CN105521521A; CN105521521B; CN109200331A

Abstract

The invention relates to a serum albumin medical gel and a preparation method thereof, and a serum albumin-containing medical product and a medical instrument kit. Dissolving serum albumin in a buffer solution with the pH range of 6.0-10.0, and changing the viscosity of the solution by adjusting the irradiation dose; dissolving the component containing electrophilic functional groups in a buffer solution with a pH range of 6.0-10.0; and mixing the irradiated serum albumin solution with the solution of the component containing the electrophilic functional group through a two-component syringe, and crosslinking the two components to form gel. The gel forming time of the two component solutions after mixing is 3-150 seconds, the swelling ratio is 40-500%, the rupture strength is not less than 50mmHg, and the degradation time is 3-30 days. The invention changes the viscosity of serum albumin by adjusting the irradiation dose, the prepared gel has high strength, good biocompatibility and degradability, and can be used as a surgical operation sealant, for example, the sealant is suitable for sealing the wound surface after lung operation.

Description

Lung sealing medical gel and preparation method and application thereof

Technical Field

The invention relates to the field of medical instruments, in particular to serum albumin medical gel and a preparation method and application thereof.

Background

Hydrogel as a biocompatible material is a three-dimensional network structure polymer with hydrophilic groups, and can be swelled by water but not dissolved by water and keep a certain shape due to the physical crosslinking and chemical crosslinking among polymer chains. In medicine, the hydrogel can be used for wound dressing, postoperative adhesion prevention, intraoperative hemostasis, tissue filling, prevention of interstitial fluid leakage or gas leakage and the like.

According to the formation principle, the hydrogel is divided into two main categories, namely a chemically crosslinked hydrogel and a physically crosslinked hydrogel. Physical crosslinking can be divided into temperature-sensitive hydrogels, molecular self-assembled hydrogels and the like. Physical hydrogels are bound by physical forces such as electrostatic interactions, hydrogen bonding, entanglement of chains, and the like. The chemical hydrogel is a three-dimensional network polymer formed by crosslinking through chemical bonds, and can be divided into crosslinking agent crosslinked hydrogel, radiation crosslinked hydrogel, photoinitiated crosslinked hydrogel and the like.

The types of hydrogels are various, and the hydrogels can be classified into in vitro gels and in vivo in situ gels according to the gel mode. In-vivo in-situ gels have the advantage of injectability and can be used not only for open surgery but also for minimally invasive surgery. The hydrogel tissue sealant may be formed by mixing two aqueous solutions, each comprising a crosslinkable component, and spraying the two solutions onto biological tissue using a mixing device to premix the two solutions prior to application to a desired site.

Surgical sealants have many potential medical applications, including wound closure, assisting sutures or staples in surgical procedures, as barriers to prevent post-surgical adhesions, and as hemostatic sealants, among others. Fibrin glue is currently used as a surgical sealant and consists of human or animal fibrinogen, thrombin and a gel-promoting agent. As a two-component adhesive, reacts rapidly to form a gel after mixing. The formed gel can adhere to tissue, stop bleeding, bridge tissue wounds, and the like until healing. However, the major disadvantages of fibrin glue are the slow dissolution rate of fibrinogen, the low gel strength and the too fast degradation time.

Serum albumin is a highly water-soluble globular protein present in plasma. Serum albumin accounts for 40% -60% of the total plasma protein, and 80% of the osmotic pressure in blood is borne by albumin. Plasma albumin is also an important protein reservoir, and can be decomposed into amino acids for tissue synthesis of various other proteins when required by the body. The lack of plasma albumin in the blood causes edema. The use of plasma albumin preparations is useful for relieving hypoproteinemia caused by liver and kidney diseases and burns. Serum albumin is an important component in blood, mainly plays a role in maintaining normal osmotic pressure of blood and conveying hydrophilic molecules, has the functions of detoxifying, participating in lipid metabolism and transportation of slightly soluble substances in blood plasma, maintaining acid-base balance of blood and the like, and is widely applied to the fields of medical clinics and biology.

Serum albumin contains a large number of amino acid residues. In the 90 s of the 20 th century, a new medical soft tissue sealant, namely Bioglue, was developed by CryoLife corporation of America through long-term research. Bioglue is an in vivo in situ gel sealant based on bovine albumin solution and glutaraldehyde solution, which is cross-linked by the reaction of amino groups of bovine serum albumin and aldehyde groups of glutaraldehyde to generate Schiff base, and has been widely used abroad for mechanically sealing leakage sites of cardiovascular and macrovascular surgeries. The sealant has been approved by food and drug administration in countries such as the united states, european union, canada, and australia. However, Bioglue residual glutaraldehyde causes cytotoxicity and even causes degeneration of nervous tissue. In recent years, there are rare reports of cases for postoperative complications after BioGlue use, such as Gabrijelcic reporting that patients develop postoperative complications of aortic insufficiency after BioGlue use Gabrijelcic T, Block of a mechanical atrial valve leaf with BioGlue a case report, Heart Surg Forum,2012,15(6): E310-312. ]; luk et al found that patients with posterior fractions of BioGlue had pseudoaneurysms [ Luk A, David TE, Butnv J.Compounds of BioGlue postdelivery for dis-infection and oral delivery. J.Clin Pathol,2012,65(11):1008-1012 ].

In addition, one problem currently encountered clinically is the frequent occurrence of lung leaks following chest surgical lung surgery. Most patients have a natural healing of the lung leak with the disappearance of the pleural cavity, adhesions in the parietal pleura, but a few patients have persistent lung leaks (PAL). The continuous lung air leakage after the operation is one of the complications after the lung operation, particularly, the contradiction caused by the lung surgery practice is more prominent along with the aging of a lung surgery patient, the emphysema and the incidence rate of Chronic Obstructive Pulmonary Disease (COPD) are gradually increased, but the corresponding medical product is not available at home at present.

Therefore, the development of a safe and effective novel serum albumin medical gel is urgent in clinical treatment.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a novel serum albumin medical product with good biodegradability, biocompatibility and safety.

The novel serum albumin medical product comprises the following components:

(1) a first liquid component comprising serum albumin at a concentration of 5% to 45% (w/v) dissolved in a buffer solution having a pH in the range of 6.0 to 10.0;

(2) a second solid component, wherein the solid component is a hydrophilic polymer containing electrophilic functional groups, and the hydrophilic polymer is selected from polyethylene glycol, polyethylene oxide or polyvinyl alcohol; wherein the mass ratio of the solid component to the serum albumin in the first liquid component is 0.3-2.

When the novel serum albumin medical product is used, the hydrophilic polymer containing the electrophilic functional groups in the second solid component is dissolved by using a buffer solution with the pH range of 6.0-10.0 to prepare a hydrophilic polymer component solution containing the electrophilic functional groups with the concentration of 5% -45% (w/v); the first liquid component is then mixed with a solution of a hydrophilic polymer component containing electrophilic functional groups and crosslinked to form a serum albumin gel. The volume ratio of the serum albumin solution to the polymer solution containing electrophilic functional groups is from 30:70 to 70:30, preferably 40:60 to 60:40, more preferably 45:55 to 55: 45.

The serum albumin of the novel serum albumin medical product can be derived from human serum albumin, bovine serum albumin, equine serum albumin, ovine serum albumin, murine serum albumin and other animals, and is preferably human serum albumin. Serum albumin can be produced by recombinant expression through genetic engineering, or can be extracted from human or animal plasma.

In the medical product, the buffer for dissolving serum albumin in the first liquid component is any buffer capable of maintaining a pH value of 6.0 to 10.0 in an aqueous solution state, and may be selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffer salts, and preferably a phosphate buffer. The buffer solution for dissolving serum albumin has pH value of 6.0-10.0, preferably pH value of 7.0-9.0; the concentration ranges from 1 to 500mM, preferably from 10 to 300mM, more preferably from 50 to 200 mM. The concentration of the protein after the serum albumin is dissolved is 5-45% (w/v), the preferable concentration range is 10-40% (w/v), and the more preferable concentration range is 20-30% (w/v).

The first liquid component, the serum albumin solution, is preferably pre-irradiated at a dose in the range of 5-45 kGy. The irradiation mode can be electron beam irradiation or gamma ray irradiation, such as high-energy ray irradiation generated by an irradiation source such as X-ray, cobalt 60, an electrostatic accelerator or a high-power electron linear accelerator. It is generally accepted that irradiation is a special "cold working" technique that sterilizes at ambient temperatures without causing an increase in the internal temperature of the irradiated article. The action of ray radiation on the article is divided into primary and secondary, the primary is ionization and chemical action of microbial intercellular substance after being irradiated by high-energy electron ray, and the secondary is that moisture is radiated and ionized to produce various free radicals and hydrogen peroxide to act with other substances in the cell. Both of these effects can impede all activities within the microbial cell, leading to microbial cell death. During the irradiation process, the gamma rays can penetrate through goods in the irradiation container and act on microorganisms to directly or indirectly destroy ribonucleic acid, protein and enzyme of the microorganisms, so that the microorganisms are killed, and the effects of disinfection and sterilization are achieved.

However, the inventors have unexpectedly found that serum albumin undergoes both radiation crosslinking and radiation degradation reactions under irradiation. Both crosslinking and degradation of serum albumin upon exposure to radiation may occur, but on the one hand this is always the main and this preference is strongly related to the molecular structure of albumin. The irradiation crosslinking reaction mainly comprises the steps of generating various free radicals after serum albumin is irradiated by rays, and forming a new connecting bond through mutual combination of the free radicals. Under the action of radiation degradation, the main chain of the serum albumin is broken, the molecular weight is reduced, and as a result, the solubility of the albumin in a solvent is increased, and the corresponding thermal stability and mechanical properties are reduced.

Generally, when the gel is used for biological tissue adhesion or sealing, if the viscosity of the gel precursor solution is too high, the gel precursor solution cannot effectively penetrate into biological tissue gaps (such as suture pinholes), cannot rapidly spread on the tissue surface, and has poor sealing or adhesion effect; if the viscosity of the gel precursor solution is too low, forming a too thin gel layer, the bond strength will also be significantly reduced, and the best sealing or bonding effect will only be achieved if the viscosity of the gel precursor solution is adequate. The viscosity of the serum albumin solution is adjusted by the irradiation method, the method has the advantages of no additive, easy operation and the like, and the gel time is shorter after the irradiated serum albumin solution is mixed with the component solution containing the electrophilic functional group. Serum albumin solutions with different viscosities can be obtained by adjusting the irradiation dose, wherein the irradiation dose of the serum albumin ranges from 5kGy to 45kGy, the more preferable irradiation dose ranges from 10kGy to 40kGy, and the more preferable irradiation dose ranges from 20kGy to 35 kGy. The larger the irradiation dose, the higher the viscosity of the serum albumin solution.

In the second solid component of the medical product, the mass ratio of the solid component to the serum albumin in the first liquid component is 0.3-2, preferably 0.5-1.5, and more preferably 0.75-1. The solid component is a hydrophilic polymer containing electrophilic functional groups selected from maleimide group (-Mal), propionaldehyde group (-ALD), succinimidyl carbonate group (-SC), succinimidyl acetate group (-SCM), succinimidyl propionate group (-SPA), succinimidyl succinate group (-SS), succinimidyl glutarate group, succinimidyl sebacate group, succinimidyl group (-NHS) and the like, and the number of the functional groups is more than 1, preferably 2 or 4. Preferred hydrophilic polymers are succinimide-terminated or succinimide succinate-terminated hydrophilic polymers with a number of electrophilic functional groups per molecule of 2 or more. The hydrophilic polymer main body can be polyethylene glycol, polyethylene oxide and polyvinyl alcohol, and is preferably polyethylene glycol. The molecular weight of the hydrophilic polymer is 1000-100000, preferably 2000-50000, more preferably 3000-20000.

More preferably, the hydrophilic polymer containing electrophilic functional groups may be selected from one or more of bis-succinimidyl propionate polyethyleneglycol, bis-succinimidyl succinate polyethyleneglycol, bis-succinimidyl glutarate polyethyleneglycol, bis-succinimidyl sebacate polyethyleneglycol, pentaerythritol polyglycol ether tetrasuccinimidyl glutaric acid, pentaerythritol polyglycol ether tetrasuccinimidyl succinic acid, pentaerythritol polyglycol ether tetrasuccinimidyl sebacic acid, having a molecular weight of 1000-100000, preferably 2000-50000, more preferably 3000-20000. The molecular weight of the bis-succinimide succinic ester polyethylene glycol is 1000-100000, preferably 2000-50000, and more preferably 3000-20000.

The buffer used for dissolving the second solid component is any buffer capable of maintaining a pH value of 6.0 to 10.0 in an aqueous solution state, and may be optionally selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffer salts, and the like, and a phosphate buffer is preferable. The pH of the buffer is preferably 6.0-8.0; the concentration of the buffer is in the range of 1-500mM, preferably 10-300mM, more preferably 50-200 mM.

The invention also aims to provide a preparation method of the serum albumin medical gel.

The preparation method of the serum albumin medical gel provided by the invention comprises the following steps:

(1) preparing a first liquid component: dissolving serum albumin in a buffer solution with the pH range of 6.0-10.0 to prepare a serum albumin solution with the concentration of 5% -45% (w/v), wherein the serum albumin is subjected to radiation treatment, and the irradiation dose range is 5-45 kGy;

(2) preparing a second liquid component: dissolving a hydrophilic polymer solid component containing electrophilic functional groups in a buffer solution with the pH range of 6.0-10.0 to prepare a hydrophilic polymer component solution containing electrophilic functional groups with the concentration of 5-45% (w/v), wherein the mass ratio of the hydrophilic polymer component containing electrophilic functional groups to the serum albumin in the first liquid component is 0.3-2;

(3) and mixing the first liquid component and the second liquid component, and crosslinking to form the serum albumin gel.

The serum albumin medical gel prepared by the method has the matrix components of human serum albumin and a polymer containing electrophilic functional groups. The source of serum albumin may be human, bovine, equine, ovine, mouse, and other animal serum albumin, preferably human serum albumin. Serum albumin can be produced by recombinant expression through genetic engineering, or can be extracted from human or animal plasma.

In the above method, the buffer for preparing the first liquid component and the second liquid component is any buffer capable of maintaining a pH value of 6.0 to 10.0 in an aqueous solution state, and may be selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, and the like, preferably a phosphate buffer. Wherein the buffer solution for dissolving serum albumin has a pH value of 6.0-10.0, preferably 7.0-9.0; the concentration ranges from 1 to 500mM, preferably from 10 to 300mM, more preferably from 50 to 200 mM. The buffer used for dissolving the component containing the electrophilic functional group preferably has a pH value of 6.0 to 10.0, preferably 6.0 to 8.0; the concentration ranges from 1 to 500mM, preferably from 10 to 300mM, more preferably from 50 to 200 mM.

In the method, the irradiation mode of the serum albumin can select electron beam irradiation and gamma ray irradiation, the serum albumin solution with different viscosities can be obtained by adjusting the irradiation dose, the irradiation dose range of the serum albumin is 5kGy-45kGy, the preferable irradiation dose is 10kGy-40kGy, and the more preferable irradiation dose is 20kGy-35 kGy. The larger the irradiation dose, the higher the viscosity of the serum albumin solution.

In the above method, the hydrophilic polymer solid component is a hydrophilic polymer containing electrophilic functional groups selected from maleimide group (-Mal), propionaldehyde group (-ALD), succinimidyl carbonate group (-SC), succinimidyl acetate group (-SCM), succinimidyl propionate group (-SPA), succinimidyl succinate group (-SS), succinimidyl glutarate group, succinimidyl sebacate group, succinimidyl (-NHS), etc., and the number of the functional groups is 1 or more, preferably 2 or 4. Preferred hydrophilic polymers are succinimide-terminated or succinimide succinate-terminated hydrophilic polymers with a number of electrophilic functional groups per molecule of 2 or more. The hydrophilic polymer main body can be polyethylene glycol, polyethylene oxide and polyvinyl alcohol, and is preferably polyethylene glycol. The molecular weight of the hydrophilic polymer is 1000-100000, preferably 2000-50000, more preferably 3000-20000.

In the above method, the ratio of the irradiated serum albumin solution to the polymer solution containing electrophilic functional groups is from 30:70 to 70:30, preferably from 40:60 to 60:40, more preferably from 45:55 to 55:45 by volume. The gel forming time of the irradiated serum albumin solution and the polymer solution containing the electrophilic functional groups is 3-150 seconds after mixing, the gel swelling rate is 40-500%, the breaking strength is not less than 50mHg, and the degradation time is 3-30 days.

The present invention also provides a medical device kit for delivering serum albumin medical gel, comprising:

(1) a first liquid component in a sealed first container, the liquid component comprising serum albumin at a concentration of 5% to 45% (w/v) dissolved in a buffer solution having a pH in the range of 6.0 to 10.0;

(2) a second solid component in a sealed second container, said solid component being a hydrophilic polymer containing electrophilic functional groups, said hydrophilic polymer being selected from the group consisting of polyethylene glycol, polyethylene oxide or polyvinyl alcohol; wherein the mass ratio of the solid component to the serum albumin in the first liquid component is 0.3-2.

(3) And a buffer solution which is independently packaged and used for dissolving the second solid component and can maintain the pH value of 6.0-10.0 in the state of aqueous solution, and the buffer solution is added into the second sealed container to dissolve the second solid component when in use.

The first liquid component, the second solid component and the buffer in the kit are as defined above. The first liquid fraction is preferably pre-irradiated with a radiation dose in the range of 5-45 kGy, preferably 10-40 kGy, more preferably 20-35 kGy. The larger the irradiation dose, the higher the viscosity of the serum albumin solution.

In a medical kit for delivering a serum albumin medical gel, a serum albumin solution can be encapsulated in a first syringe cavity of a two-component syringe, while a hydrophilic polymer solid component containing electrophilic functional groups is encapsulated in a second syringe cavity. When the serum albumin gel is actually used, a proper buffer solution is extracted and added into the cavity of the second syringe to dissolve the solid components, the liquid components in the first syringe and the second syringe are mixed in the cavity of the mixing head by applying pressure through the push rod, the serum albumin gel is formed by crosslinking, and finally the serum albumin gel is sprayed on wounds of various surgical operations of a human body through the spray head to play roles of adhesion, hemostasis, leakage prevention, adhesion prevention and the like.

The medical gel of the present invention can be detected by the following method.

And (3) gel time detection: the gel curing time reflects the speed of in-situ forming of the gel, and directly influences the operation of the next operation after the clinical gel is used. The gel time was measured by inverting the tube. Respectively filling the irradiated serum albumin solution and the component solution containing the electrophilic functional group into a two-component injector, injecting into a centrifuge tube, placing in a 37 ℃ constant-temperature water bath kettle, timing by using a stopwatch, and taking the time between the solution flowing in the centrifuge tube and the non-flowing state after the centrifuge tube is inverted as the gel time.

And (3) detecting the swelling ratio: the swelling ratio refers to the percentage of mass increase after the gel swells in physiological saline to reach equilibrium after being crosslinked. The detection method comprises the following steps: and respectively filling the irradiated serum albumin solution and the component solution containing the electrophilic functional groups into a two-component injector, injecting the two-component injector into a template, gelling, and weighing. The gel was transferred to a centrifuge tube, physiological saline was added, samples were taken every 12 hours, surface moisture was removed with filter paper, and weighed until the mass did not increase any more. Swelling ratio ═ (mass at swelling equilibrium-mass before swelling)/mass before swelling × 100%.

Detection of rupture strength: in addition to gel time and swelling ratio, the breaking strength of the gel is also important, which reflects the mechanical properties of the gel during use. The detection method comprises the following steps: a hole with the diameter of about 0.2cm is punched on a fresh pig casing, the irradiated serum albumin solution and the component solution containing electrophilic functional groups are respectively filled into a two-component syringe, the two-component syringe is sprayed on the hole to form gel, the dosage of the gel is about 2mL, the gel is pressurized by normal saline until the gel is damaged, and the maximum pressure number on a digital reader connected with a sensor is recorded.

In vitro degradation time detection: respectively filling the irradiated serum albumin solution and the component solution containing electrophilic functional groups into a two-component injector, injecting the two-component injector into a template, transferring the two-component injector into a centrifuge tube after gelation, adding normal saline, and recording the time as the degradation time in vitro of the gel when the two-component injector is observed to be invisible to naked eyes every day.

The invention uses a compound containing electrophilic functional groups as a cross-linking agent of serum albumin, which fundamentally improves the problem of tissue compatibility. Polyethylene glycol is highly hydrophilic and non-immunogenic. After oxidation by cytochrome P450 system, PEG is decomposed into small molecular PEG, and then excreted via bile. The PEG product can be safely degraded and absorbed in vivo, does not produce rejection reaction, and medical equipment products prepared from medical polyethylene glycol (PEG) products can be widely applied to materials for adhesion, hemostasis, leakage prevention, adhesion prevention and the like of wounds in various surgical operations of human bodies. The irradiation mode is adopted to adjust the viscosity of the serum albumin solution, so that the clinical operability is obviously improved, and the gel speed is improved, therefore, the method has obvious progress compared with the existing medical gel.

Therefore, another object of the present invention is to provide the use of the serum albumin medical product, medical gel or medical device kit in the adhesion, hemostasis, leakage prevention or adhesion prevention of wounds in various surgical operations of human body. The hydrogel can be used for sealing defective tissues in the processes of cardiovascular surgery, general surgery, orthopedics, neurosurgery, ophthalmology or orthopedics surgery in medicine. Can reduce the bleeding of the wound surface of the tissue and the bleeding of small veins, promote the healing of wounds, prevent tissue adhesion, seal defective tissues and promote the healing of chronic ulcer surfaces, for example, sealing for repairing a dura mater in neurosurgery (skull and spinal surgery) and reducing the leakage of cerebrospinal fluid after the surgery; sealing of vascular reconstructive sites in cardiovascular surgery; the device is used for reducing the leakage of gas after the fiber suture of lung tissues in the chest surgical lung resection operation; sealing for lens perforation, eyelid surgery, lacrimal gland and conjunctival repair in ophthalmology; used for postoperative adhesion prevention in surgery; can also be used for fixing hernia patches; and sealing the anastomotic stoma after the intestinal anastomosis operation.

In a preferred embodiment, the present invention provides the use of a novel serum albumin medical product, medical gel or medical device kit for the manufacture of a medical device for wound closure following pulmonary surgery. The part needing spraying is cleaned by sterile physiological saline, accumulated blood is washed or sucked away, and then the prepared serum albumin medical gel is coated on the target position by stably pushing the push rod to cover the air-leaking tissue. After 2 minutes of coating, the coated part can be tested whether the air leaks or not by using a normal saline immersion method, for example, the air leaks, and the product can be sprayed again to seal the air leakage.

The following technical solutions summarize the present invention.

1. A serum albumin medical product comprises the following components:

2. The product according to claim 1, characterized in that: when the serum albumin medical product is used, the hydrophilic polymer containing the electrophilic functional groups in the second solid component is dissolved by using a buffer solution with the pH range of 6.0-10.0 to prepare a hydrophilic polymer component solution containing the electrophilic functional groups with the concentration of 5% -45% (w/v); the first liquid component is then mixed with a solution of a hydrophilic polymer component containing electrophilic functional groups and crosslinked to form a serum albumin gel.

3. The product according to claim 2, characterized in that: the volume ratio of the serum albumin solution to the polymer solution containing the electrophilic functional groups is 30:70 to 70: 30.

4. The product according to claim 3, characterized in that: the volume ratio of the serum albumin solution to the polymer solution containing the electrophilic functional groups is 40:60 to 60: 40.

5. The product according to claim 4, characterized in that: the volume ratio of the serum albumin solution to the polymer solution containing the electrophilic functional groups is 45:55 to 55: 45.

6. The product according to claim 1, characterized in that: the source of the serum albumin is the serum albumin of animals such as human, cattle, horses, sheep, mice and the like.

7. The product according to claim 6, characterized in that: the serum albumin is human serum albumin.

8. The product according to claim 1, characterized in that: serum albumin can be produced by recombinant expression through genetic engineering, or can be extracted from human or animal plasma.

9. The product according to claim 1, characterized in that: the buffer for dissolving serum albumin in the first liquid component is any buffer capable of maintaining a pH value of 6.0 to 10.0 in an aqueous solution state, and may be selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffer salts.

10. The product according to claim 9, characterized in that: the buffer solution is phosphate buffer solution.

11. The product according to claim 9, characterized in that: the pH value of the buffer solution is 7.0-9.0.

12. The product according to claim 9, characterized in that: the concentration range of the buffer solution is 1-500 mM.

13. The product according to claim 12, characterized in that: the concentration range of the buffer solution is 10-300 mM.

14. The product according to claim 13, characterized in that: the concentration range of the buffer solution is 50-200 mM.

15. The product according to claim 1, characterized in that: the protein concentration of the first liquid component after dissolution of serum albumin is 5-45% (w/v).

16. The product according to claim 15, characterized in that: the protein concentration of the first liquid component after the serum albumin is dissolved is 10-40% (w/v).

17. The product of claim 16, characterized in that: the protein concentration of the first liquid component after dissolution of serum albumin is 20-30% (w/v).

18. The product according to claim 1, characterized in that: in the first liquid component, the serum albumin solution is pre-treated by irradiation with a dose in the range of 5kGy to 45 kGy.

19. The product according to claim 18, characterized in that: in the first liquid component, the serum albumin solution is pre-treated by irradiation with a dose in the range of 10kGy to 40 kGy.

20. The product according to claim 19, characterized in that: in the first liquid component, the serum albumin solution is pre-treated by irradiation with a dose in the range of 20kGy to 35 kGy.

21. The product according to claim 18, characterized in that: the irradiation mode is electron beam irradiation or gamma ray irradiation.

22. The product according to claim 21, characterized in that: the irradiation mode is high-energy ray irradiation generated by an X-ray, cobalt 60, an electrostatic accelerator or a high-power electron linear accelerator and other irradiation sources.

23. The product according to claim 1, characterized in that: the mass ratio of the second solid component to the serum albumin in the first liquid component is 0.3-2.

24. The product according to claim 23, characterized in that: the mass ratio of the second solid component to the serum albumin in the first liquid component is 0.5-1.5.

25. The product of claim 24, characterized in that: the mass ratio of the second solid component to the serum albumin in the first liquid component is 0.75-1.

26. The product according to claim 1, characterized in that: the second solid component is a hydrophilic polymer containing electrophilic functional groups, the electrophilic functional groups are selected from maleimide group (-Mal), propionaldehyde group (-ALD), succinimidyl carbonate group (-SC), succinimidyl acetate group (-SCM), succinimidyl propionate group (-SPA), succinimidyl succinate group (-SS), succinimidyl glutarate group, succinimidyl sebacate group, succinimidyl (-NHS) and the like, and the number of the functional groups is more than 1.

27. The product of claim 26, wherein: in the hydrophilic polymer, the number of the functional groups is 2 or 4.

28. The product of claim 26, wherein: the hydrophilic polymer is a succinimide end-capped or succinimide succinate end-capped hydrophilic polymer, and the number of electrophilic functional groups per molecule is more than 2.

29. The product of claim 26, wherein: the main body of the hydrophilic polymer is polyethylene glycol, polyoxyethylene and polyvinyl alcohol.

30. The product according to claim 29, characterized in that: the main body of the hydrophilic polymer is polyethylene glycol.

31. The product of claim 26, wherein: the molecular weight of the hydrophilic polymer is 1000-100000.

32. The product according to claim 31, characterized in that: the molecular weight of the hydrophilic polymer is 2000-50000.

33. The product according to claim 32, characterized in that: the molecular weight of the hydrophilic polymer is 3000-20000.

34. The product of claim 26, wherein: the hydrophilic polymer containing the electrophilic functional groups can be selected from one or more of bis-succinimide-propionate-based polyethylene glycol, bis-succinimide-succinate-based polyethylene glycol, bis-succinimide-glutarate-based polyethylene glycol, bis-succinimide-sebacate-based polyethylene glycol, pentaerythritol polyglycol ether tetrasuccinimide glutaric acid, pentaerythritol polyglycol ether tetrasuccinimide succinic acid, pentaerythritol polyglycol ether tetrasuccinimide sebacic acid, and the molecular weight is 1000-100000.

35. The product of claim 34, wherein: the molecular weight of the hydrophilic polymer containing electrophilic functional groups is 2000-50000.

36. The product according to claim 35, characterized in that: the molecular weight of the hydrophilic polymer containing electrophilic functional groups is 3000-20000.

37. The product of claim 34, wherein: the hydrophilic polymer containing the electrophilic functional groups is bis-succinimide succinic ester polyethylene glycol, and the molecular weight is 1000-100000.

38. The product of claim 37, wherein: the molecular weight of the bis-succinimide succinic ester polyethylene glycol is 2000-50000.

39. The product of claim 37, wherein: the molecular weight of the bis-succinimide succinic ester polyethylene glycol is 3000-20000.

40. The product according to claim 2, characterized in that: the buffer used for dissolving the second solid component is any buffer capable of maintaining a pH value of 6.0 to 10.0 in an aqueous solution state, and may be optionally selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffer salts.

41. The product according to claim 40, characterized in that: the buffer solution is phosphate buffer solution.

42. The product according to claim 41, characterized in that: the pH value of the buffer solution is 6.0-8.0.

43. The product of claim 39, wherein: the concentration range of the buffer solution is 1-500 mM.

44. The product according to claim 43, characterized in that: the concentration range of the buffer solution is 10-300 mM.

45. The product of claim 44, wherein: the concentration range of the buffer solution is 50-200 mM.

46. A preparation method of serum albumin medical gel comprises the following steps:

47. The method of claim 46, wherein: in the method, the source of the serum albumin in the step (1) is the serum albumin of animals such as human, cattle, horses, sheep, mice and the like.

48. The method of claim 47, wherein: in the step (1), the serum albumin is human serum albumin.

49. The method of claim 48, wherein: the serum albumin in step (1) of the method can be produced by genetic engineering recombinant expression, or can be extracted from human or animal plasma.

50. The method of claim 46, wherein: the buffer used for dissolving serum albumin in step (1) of the method is any buffer capable of maintaining a pH value of 6.0 to 10.0 in an aqueous solution state, and may be optionally selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffer salts.

51. The method of claim 50, wherein: the buffer solution in the step (1) of the method is a phosphate buffer solution.

52. The method of claim 46, wherein: the pH value of the buffer solution in the step (1) of the method is 7.0-9.0.

53. The method of claim 46, wherein: the concentration of the buffer in step (1) of the method is in the range of 1-500 mM.

54. The method of claim 53, wherein: the concentration of the buffer in step (1) of the method is in the range of 10-300 mM.

55. The method of claim 54, wherein: the concentration of the buffer in step (1) of the method is in the range of 50-200 mM.

56. The method of claim 46, wherein: in the method, the concentration of the protein dissolved by the serum albumin in the step (1) is 5-45% (w/v).

57. The method of claim 56, wherein: in the method, the concentration of the protein dissolved by the serum albumin in the step (1) is 10-40% (w/v).

58. The method of claim 57, wherein: in the method, the concentration of the protein dissolved by the serum albumin in the step (1) is 20-30% (w/v).

59. The method of claim 46, wherein: in the step (1), the serum albumin solution is pre-treated by irradiation, and the irradiation dose range is 10kGy-40 kGy.

60. The method of claim 60, wherein: in the step (1), the serum albumin solution is treated in advance by irradiation, and the irradiation dose range is 20kGy-35 kGy.

61. The method of claim 46, wherein: in the step (1), the irradiation mode is electron beam irradiation or gamma ray irradiation.

62. The method of claim 46, wherein: in the step (1), the irradiation mode is high-energy ray irradiation generated by an X-ray, cobalt 60, an electrostatic accelerator or a high-power electron linear accelerator and other irradiation sources.

63. The method of claim 46, wherein: in step (2), the mass ratio of the hydrophilic polymer component containing electrophilic functional groups in the second liquid component to the serum albumin in the first liquid component is 0.5-1.5.

64. The method of claim 63, wherein: in the step (2), the mass ratio of the hydrophilic polymer component containing electrophilic functional groups in the second liquid component to the serum albumin in the first liquid component is 0.75-1.

65. The method of claim 46, wherein: in the step (2), the electrophilic functional groups of the hydrophilic polymer in the second liquid component are selected from maleimide group (-Mal), propionaldehyde group (-ALD), succinimidyl carbonate group (-SC), succinimidyl acetate group (-SCM), succinimidyl propionate group (-SPA), succinimidyl succinate group (-SS), succinimidyl glutarate group, succinimidyl sebacate group, succinimidyl (-NHS) and the like, and the number of the functional groups is 1 or more.

66. The method of claim 65, wherein: in step (2) of the method, the number of electrophilic functional groups of the hydrophilic polymer in the second liquid component is 2 or 4.

67. The method of claim 65, wherein: in the step (2), the hydrophilic polymer in the second liquid component is a succinimide-terminated or succinimide-succinate-terminated hydrophilic polymer, and the number of electrophilic functional groups per molecule is more than 2.

68. The method of claim 46, wherein: in the step (2), the hydrophilic polymer in the second liquid component is polyethylene glycol, polyethylene oxide or polyvinyl alcohol.

69. The method of claim 68, wherein: in step (2), the hydrophilic polymer in the second liquid component is mainly polyethylene glycol.

70. The method of claim 46, wherein: in the step (2), the molecular weight of the hydrophilic polymer in the second liquid component is 1000-100000.

71. The method of claim 70, wherein: in step (2) of the method, the molecular weight of the hydrophilic polymer in the second liquid component is 2000-50000.

72. The method of claim 71, wherein: in step (2) of the process, the molecular weight of the hydrophilic polymer in the second liquid component is 3000-20000.

73. The method of claim 46, wherein: in the step (2), the hydrophilic polymer containing electrophilic functional groups in the second liquid component may be one or more selected from bis-succinimide-propionate-based polyethylene glycol, bis-succinimide-succinate-based polyethylene glycol, bis-succinimide-glutarate-based polyethylene glycol, bis-succinimide-sebacate-based polyethylene glycol, pentaerythritol polyethylene glycol ether tetrasuccinimide glutaric acid, pentaerythritol polyethylene glycol ether tetrasuccinimide succinic acid, pentaerythritol polyethylene glycol ether tetrasuccinimide sebacic acid, and has a molecular weight of 1000 to 100000.

74. The method of claim 73, wherein: in step (2) of the method, the molecular weight of the hydrophilic polymer in the second liquid component is 2000-50000.

75. The method of claim 74, wherein: in step (2) of the process, the molecular weight of the hydrophilic polymer in the second liquid component is 3000-20000.

76. The method of claim 73, wherein: in the step (2), the hydrophilic polymer containing the electrophilic functional groups in the second liquid component is bis-succinimide succinate polyethylene glycol with a molecular weight of 1000-100000.

77. The method of claim 76, wherein: in the step (2), the molecular weight of the bis-succinimidyl succinate polyethylene glycol is 2000-50000.

78. The method of claim 77, wherein: in the step (2), the molecular weight of the bis-succinimide-succinate-based polyethylene glycol is 3000-20000.

79. The method of claim 46, wherein: in the step (2), the buffer for dissolving the hydrophilic polymer is any buffer capable of maintaining a pH value of 6.0 to 10.0 in an aqueous solution state, and may be selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffer salts.

80. The method of claim 79, wherein: in the step (2), the buffer solution is phosphate buffer solution.

81. The method of claim 79, wherein: in the step (2), the pH value of the buffer solution is 6.0-8.0.

82. The method of claim 79, wherein: in step (2) of the method, the concentration of the buffer solution is in the range of 1-500 mM.

83. The method of claim 82, wherein: in step (2) of the method, the concentration of the buffer solution is in the range of 10-300 mM.

84. The method of claim 83, wherein: in step (2) of the method, the concentration of the buffer solution is in the range of 50-200 mM.

85. The method of claim 46, wherein: in step (3), the volume ratio of the first liquid component to the second liquid component is 30:70 to 70: 30.

86. The method of claim 85, wherein: in step (3) of the method, the volume ratio of the first liquid component to the second liquid component is 40:60 to 60:40 or 45:55 to 55: 45.

87. A serum albumin gel prepared according to the method of any one of claims 46-86.

88. A medical device kit for delivering a serum albumin medical gel, comprising:

89. The kit of claim 88, wherein: the source of serum albumin in the first liquid component of the kit is human, bovine, equine, ovine, murine, etc. serum albumin.

90. The kit according to claim 89, characterized in that: the serum albumin in the first liquid component of the kit is human serum albumin.

91. The kit of claim 88, wherein: the serum albumin in the first liquid component of the kit may be produced by genetically engineered recombinant expression or may be extracted from human or animal plasma.

92. The kit of claim 88, wherein: the buffer in the first liquid component of the kit is any buffer capable of maintaining a pH of 6.0 to 10.0 in an aqueous solution state, and may optionally be selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffer salts, and the like.

93. The kit of claim 92, wherein: the buffer in the first liquid component of the kit is a phosphate buffer.

94. The kit of claim 92, wherein: the pH value of the buffer solution in the first liquid component of the kit is 7.0-9.0.

95. The kit of claim 92, wherein: the concentration of the buffer in the first liquid component of the kit is in the range of 1-500 mM.

96. The kit of claim 95, wherein: the concentration of the buffer in the first liquid component of the kit is in the range of 10-300 mM.

96. The kit of claim 96, wherein: the concentration of the buffer in the first liquid component of the kit is in the range of 50-200 mM.

97. The kit of claim 88, wherein: the protein concentration of serum albumin in the first liquid component of the kit is between 5% and 45% (w/v).

98. The kit according to claim 97, characterized in that: the protein concentration of serum albumin in the first liquid component of the kit is between 10% and 40% (w/v).

99. The kit of claim 98, wherein: the protein concentration of serum albumin in the first liquid component of the kit is between 20% and 30% (w/v).

100. The kit of claim 88, wherein: the first liquid component of the kit is pre-treated by irradiation with a dose in the range of 5kGy to 45 kGy.

101. The kit of claim 100, wherein: the first liquid component of the kit is pre-treated by irradiation with a dose in the range of 10kGy to 40 kGy.

102. The kit of claim 101, wherein: the first liquid component of the kit is pre-treated by irradiation at a dose in the range of 20kGy to 35 kGy.

103. The kit of claim 100, wherein: the first liquid component of the kit is pre-treated by irradiation, which is electron beam irradiation or gamma ray irradiation.

104. The kit of claim 103, wherein: the first liquid component of the kit is pre-treated by irradiation, wherein the irradiation is performed by high-energy rays generated by irradiation sources such as X rays, cobalt 60, an electrostatic accelerator or a high-power electron linear accelerator.

105. The kit of claim 88, wherein: the mass ratio of the hydrophilic polymer component containing electrophilic functional groups in the second solid component of the kit to the serum albumin in the first liquid component is 0.5-1.5.

106. The kit of claim 105, wherein: the mass ratio of the hydrophilic polymer component containing electrophilic functional groups in the second solid component of the kit to the serum albumin in the first liquid component is 0.75-1.

107. The kit of claim 88, wherein: in the second solid component of the kit, the electrophilic functional groups of the hydrophilic polymer are selected from maleimide group (-Mal), propionaldehyde group (-ALD), succinimidyl carbonate group (-SC), succinimidyl acetate group (-SCM), succinimidyl propionate group (-SPA), succinimidyl succinate group (-SS), succinimidyl glutarate group, succinimidyl sebacate group, succinimidyl group (-NHS) and the like, and the number of the functional groups is more than 1.

108. The kit of claim 107, wherein: in the second solid component of the kit, the number of electrophilic functional groups of the hydrophilic polymer is 2 or 4.

109. The kit of claim 107, wherein: in the second solid component of the kit, the hydrophilic polymer is a succinimide-terminated or succinimide succinate-terminated hydrophilic polymer, and the number of electrophilic functional groups per molecule is more than 2.

110. The kit of claim 107, wherein: in the second solid component of the kit, the main body of the hydrophilic polymer is polyethylene glycol, polyethylene oxide and polyvinyl alcohol.

111. The kit of claim 110, wherein: in the second solid component of the kit, the main body of the hydrophilic polymer is polyethylene glycol.

112. The kit of claim 107, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 1000-100000.

113. The kit of claim 112, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 2000-50000.

114. The kit of claim 114, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 3000-20000.

115. The kit of claim 107, wherein: in the second solid component of the kit, the hydrophilic polymer containing electrophilic functional groups can be selected from one or more of bis-succinimide-propionate-based polyethylene glycol, bis-succinimide-succinate-based polyethylene glycol, bis-succinimide-glutarate-based polyethylene glycol, bis-succinimide-sebacate-based polyethylene glycol, pentaerythritol polyglycol ether tetrasuccinimide glutaric acid, pentaerythritol polyglycol ether tetrasuccinimide succinic acid, pentaerythritol polyglycol ether tetrasuccinimide sebacic acid, and the molecular weight is 1000-100000.

116. The kit of claim 115, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 2000-50000.

117. The kit of claim 116, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 3000-20000.

118. The kit of claim 115, wherein: in the second solid component of the kit, the hydrophilic polymer containing the electrophilic functional group is bis-succinimide succinate polyethylene glycol with the molecular weight of 1000-100000.

119. The kit of claim 118, wherein: the molecular weight of the bis-succinimidyl succinate polyethylene glycol in the second solid component of the kit is 2000-50000.

120. The kit of claim 119, wherein: the molecular weight of the bis-succinimide succinate polyethylene glycol in the second solid component of the kit is 3000-20000.

121. The kit of claim 88, wherein: the buffer in the kit is any buffer capable of maintaining a pH value of 6.0-10.0 in an aqueous solution state, and may be selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffer salts.

122. The kit of claim 121, wherein: the buffer solution in the kit is phosphate buffer solution.

123. The kit of claim 121, wherein: the pH value of the buffer solution in the kit is 6.0-8.0.

124. The kit of claim 121, wherein: the concentration of buffer in the kit ranges from 1 to 500 mM.

125. The kit of claim 124, wherein: the concentration of buffer in the kit ranges from 10 to 300 mM.

126. The kit of claim 125, wherein: the concentration of buffer in the kit ranges from 50 to 200 mM.

127. The kit of claim 88, wherein: when the kit is actually used, a proper buffer solution is extracted and added into the cavity of the second syringe to dissolve the solid components, the liquid components in the first syringe and the second syringe are mixed in the cavity of the mixing head by applying pressure through the push rod, and serum albumin gel is formed by crosslinking; wherein the volume ratio of the liquid component in the first syringe chamber to the liquid component in the second syringe chamber is from 30:70 to 70: 30.

128. The kit of claim 127, wherein: when the kit is actually used, a proper buffer solution is extracted and added into the cavity of the second syringe to dissolve the solid components, the liquid components in the first syringe and the second syringe are mixed in the cavity of the mixing head by applying pressure through the push rod, and serum albumin gel is formed by crosslinking; wherein the volume ratio of the liquid component in the first syringe chamber to the liquid component in the second syringe chamber is from 40:60 to 60: 40.

129. The kit of claim 128, wherein: when the kit is actually used, a proper buffer solution is extracted and added into the cavity of the second syringe to dissolve the solid components, the liquid components in the first syringe and the second syringe are mixed in the cavity of the mixing head by applying pressure through the push rod, and serum albumin gel is formed by crosslinking; wherein the volume ratio of the liquid component in the first syringe chamber to the liquid component in the second syringe chamber is from 45:55 to 55: 45.

130. Use of the serum albumin medical product of any one of claims 1 to 46, the serum albumin gel of claim 87, or the medical device kit of any one of claims 88 to 129 for adhering, stopping bleeding, preventing leakage, or preventing adhesion of wounds in various surgical procedures on the human body.

131. The use according to claim 130 for sealing defective tissue in medical procedures for cardiovascular, general surgery, orthopedics, neurosurgery, ophthalmology, or orthopedics.

132. The use according to claim 131 for sealing in neurosurgery (in cranial, spinal surgery) for dural repair, in cardiovascular surgery for vascular reconstruction, in chest surgery for pulmonary resection with less leakage of gas after the suturing of lung tissue fibers, in ophthalmology for crystal perforation, eyelid surgery, lacrimal gland and conjunctiva repair, in surgery for adhesion prevention after surgery, fixation of hernia patches and sealing of anastomotic stoma after enteroanastomosis.

133. Use of the serum albumin medical product of any one of claims 1-46, the serum albumin gel of claim 87, or the medical device kit of any one of claims 88-129 in the manufacture of a medical device for wound closure following pulmonary surgery.

Drawings

FIG. 1 shear viscosity of human serum albumin solution as a function of shear rate after non-irradiation, 10kGy, 25kGy and 35kGy dose electron beam irradiation.

Fig. 2 is a schematic view of a two-component injector. The two-component injector consists of five parts, namely an injector cavity of a component 1, an injector cavity of a component 2, a push rod, a mixing head and a spray head.

FIG. 3 bis-succinimide succinate-based polyethylene glycol molecular structure

FIG. 4 bis-succinimidyl glutarate polyethylene glycol molecular structure

FIG. 5 molecular Structure of pentaerythritolpolyglycol Ether Tetrasuccinimide glutaric acid

FIG. 6 molecular Structure of pentaerythritol polyglycol ether tetrasuccinimide sebacic acid

Detailed Description

Example 1

0.4g (20%, w/v) of plasma-derived human serum albumin was weighed and dissolved in 2mL of phosphate buffer (10mM, pH 7.4) prepared in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. The zero shear viscosity of the human serum albumin solution before irradiation was 33 mPas. Irradiating the human serum albumin solution from the blood plasma by electron beams, wherein the irradiation dose is respectively 10kGy, 25kGy, 35kGy and 55 kGy. The viscosity of human serum albumin solution after non-irradiation, 10kGy, 25kGy and 35kGy electron beam irradiation as a function of shear rate is shown in FIG. 1. The human serum albumin solution formed a gel after electron beam irradiation at a dose of 55 kGy.

0.3g of bis-succinimidyl succinate polyethylene glycol having a molecular weight of 5000 was weighed, dissolved in 2ml of phosphate buffer (10mM, pH 8.4) prepared in deionized water, and vortexed to dissolve it as a clear liquid.

The blood serum albumin solution and the disuccinimidyl succinate polyethylene glycol solution with the same volume are respectively filled into a two-component injector (figure 2), and the blood serum albumin gel is formed by cross-linking after spraying. The gel time after mixing the non-irradiated human serum albumin solution and the disuccinimidyl succinate polyethylene glycol solution is 48 seconds, and the gel time after mixing the non-irradiated human serum albumin solution and the disuccinimidyl succinate polyethylene glycol solution after irradiation of electron beams with doses of 10kGy, 25kGy and 35kGy is 45 seconds, 29 seconds and 25 seconds respectively.

Example 2

Recombinant human serum albumin (0.4 g, 20%, w/v) was weighed and dissolved in 2ml sodium bicarbonate-sodium carbonate buffer (20mM, pH 9.4) in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. The recombinant human serum albumin is irradiated by electron beams, and the irradiation dose is 25 kGy.

0.25g of polyethylene glycol bis-succinimidyl succinate (MW 4000D, FIG. 3) was weighed out, dissolved in 2mL of phosphate buffer (20mM, pH 8.04) in deionized water and vortexed to dissolve it as a clear liquid.

And respectively filling the irradiated recombinant human serum albumin solution and the disuccinimidyl propionate polyethylene glycol solution in equal volume into a two-component injector, and performing cross-linking after spraying to form serum albumin gel. The gel time of the recombinant human serum albumin solution and the disuccinimidyl propionate polyethylene glycol solution after mixing is 15 seconds, and the rupture strength reaches 288 mmHg.

Example 3

0.5g (25%, w/v) of plasma-derived human serum albumin was weighed and dissolved in 2ml of phosphate buffer (20mM, pH 8.67) prepared in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. The recombinant human serum albumin is irradiated by electron beams, and the irradiation dose is 15 kGy.

0.3g of bis-succinimidyl succinate-based polyethylene glycol (molecular weight 3500D) was weighed, dissolved in 2ml of phosphate buffer (20mM, pH 8.04) prepared in deionized water, and vortexed to dissolve it as a clear liquid.

And respectively filling the irradiated human serum albumin solution from the plasma and the disuccinimidyl succinate polyethylene glycol solution into a two-component injector, and crosslinking to form serum albumin gel after spraying, wherein the gel time is 36 seconds, and the rupture strength reaches 295 mmHg.

Example 4

12 healthy New Zealand white rabbits of the common grade are divided into 2 groups, namely a serum albumin gel group and a blank group, randomly with male and female being irresistible and the weight of 2.5-3.0 kg. The 2 groups of New Zealand white rabbits are anesthetized by 3mL/kg of sodium pentobarbital (mass concentration is 1%) in ear margin veins and then intubated by an air tube, and then are connected with a respirator to control the respiration, wherein the tidal volume is 80mL, and the respiratory frequency is 30 times/min.

The normal right side is opened, the tissue at the margin of the lung lobe is cut off, the wound surface is about 1 square centimeter, and at least one broken end of a bronchiole with the diameter of about 1 millimeter is visible. The wound surface of the blank control group was directly closed without any treatment. The serum albumin gel group wound surface was sprayed with gel (obtained in example 3) at a thickness of about 2mm, ranging over 2cm from the wound edge, and at a gel dosage of about 2 mL.

The blank control group 6 New Zealand white rabbits died due to respiratory failure caused by continuous air leakage within 1-4h after operation. Serum albumin gel group 6 new zealand white rabbits survived. During positive pressure ventilation, the airway pressure is 10cmH₂And when O is used, the air leakage of the untreated pulmonary wound surface is obvious. After spraying serum albumin gel on the wound surface, the airway pressure reaches 36cmH₂And when O is used, no obvious air leakage appears on the wound surface.

Example 5

In the traditional ophthalmic surgery, the traditional ophthalmic suture can cause the wound surface of the cornea, and the risk of infection and vascularization also exists at the suture position.

The preparation method of the hydrogel for sealing eyes comprises the following steps: 0.4g (20%, w/v) of plasma-derived human serum albumin was weighed and dissolved in 2ml of phosphate buffer (20mM, pH 9.0) prepared in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. The recombinant human serum albumin is irradiated by electron beams, and the irradiation dose is 25 kGy.

0.15g of bis-succinimidyl succinate-based polyethylene glycol (SS-PEG-SS, molecular weight 8000D) was weighed, dissolved in 2ml of phosphate buffer (20mM, pH 7.0) prepared in deionized water, and vortexed to dissolve it as a clear liquid.

And respectively filling the irradiated human serum albumin solution from the plasma source and the disuccinimidyl succinate polyethylene glycol solution into a two-component injector, and crosslinking to form serum albumin gel after spraying, wherein the gel time is 36 seconds, the breaking strength of the prepared serum albumin gel reaches 225mHg, and the in-vitro degradation time is 4 days.

Example 6

Adhesions are abnormal attachments of tissue to the tissue surface and are an excessive physiological response of the peritoneum to injury. Adhesions are often beneficial as part of the wound healing process, but are also a significant cause of small bowel obstruction, chronic pelvic pain after gynecological surgery, and also increase the difficulty of re-surgery for patients. The preparation method of the hydrogel for preventing the adhesion of the tissues comprises the following steps:

0.3g (2%, w/v) of plasma-derived human serum albumin was weighed and dissolved in 2ml of phosphate buffer (10mM, pH 8.0) prepared in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. Irradiating the human serum albumin solution from the blood plasma by electron beams, wherein the irradiation dose is 25 kGy.

0.2g of bis-succinimidyl glutarate-based polyethylene glycol (SG-PEG-SG, molecular weight 10000D, FIG. 4) was weighed, dissolved in 2ml of phosphate buffer (10mM, pH 7.0) prepared from deionized water, and vortexed to dissolve it into a clear liquid.

And respectively filling the irradiated human serum albumin solution from the plasma source and the disuccinimidyl glutarate-based polyethylene glycol solution into a two-component injector, and performing cross-linking after spraying to form serum albumin gel. The gel time of the blood plasma source human serum albumin solution and the disuccinimidyl valerate polyethylene glycol solution after mixing is 45 seconds, the swelling rate of the prepared serum albumin gel is 180 percent, the breaking strength reaches 195mHg, and the in vitro degradation time is 6 days.

Example 7

The oozing of blood at the sealed part of cardiovascular surgery has been a difficult problem in the medical field. Ligation and sealing are not completely problematic for common large vessel bleeding. The bioprotein gel is the most widely used sealing hemostatic gel at present, but has the defects of inconvenient use and low sealing strength of the gel. The preparation method of the hydrogel for sealing blood vessels comprises the following steps:

bovine Serum Albumin (BSA) 0.4g (20%, w/v) was weighed and dissolved in 2ml sodium bicarbonate-sodium carbonate buffer (20mM, pH 9.0) prepared in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. Bovine serum albumin was irradiated with electron beam at a dose of 25 kGy.

0.5g of pentaerythritolpolyglycolether tetrasuccinimide glutaric acid (4-arm-PEG-SG, molecular weight 10000D, FIG. 5) was weighed out, dissolved in 2mL of phosphate buffer (20mM, pH 7.0) made up of deionized water, and vortexed to dissolve it as a clear liquid.

And respectively filling the irradiated bovine serum albumin solution and pentaerythritol polyglycol ether tetrasuccinimide glutaric acid solution into a two-component injector, and performing cross-linking after spraying to form serum albumin gel. The gel time of the mixed solution of bovine serum albumin and pentaerythritol polyglycol ether tetrasuccinimide glutaric acid is 16 seconds, the swelling rate of the prepared serum albumin gel is 168 percent, the breaking strength reaches 348mmHg, and the in vitro degradation time is 13 days.

Example 8

Cerebrospinal fluid leakage is a common complication after cranial and spinal surgery. Since nerves near the skull and spine are sensitive to compression due to tissue inflammation or swelling of surgical implant materials (e.g., artificial dura mater), hydrogels with low swelling ratios are needed to minimize compression on the tissue. The preparation method of the sealing hydrogel for preventing cerebrospinal fluid leakage comprises the following steps: recombinant human serum albumin (0.5 g, 20%, w/v) was weighed and dissolved in 2ml of phosphate buffer (10mM, pH 9.0) in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. Irradiating the recombinant human serum albumin solution by electron beams, wherein the irradiation dose is 25 kGy.

0.5g of pentaerythritolpolyglycolether tetrasuccinimide glutaric acid (4-arm-PEG-SG, molecular weight 10000D) was weighed out, dissolved in 2ml of phosphate buffer (10mM, pH 7.4) made up of deionized water, and vortexed to dissolve it into a clear liquid.

And respectively filling the irradiated recombinant human serum albumin solution and pentaerythritol polyglycol ether tetrasuccinimide glutaric acid solution into a two-component injector, and performing cross-linking after spraying to form serum albumin gel. The gel time of the recombined human serum albumin solution and pentaerythritol polyglycol ether tetrasuccinimide glutaric acid solution after mixing is 15 seconds, the swelling rate of the prepared serum albumin gel is 105 percent, the breaking strength reaches 360mmHg, and the in vitro degradation time is 20 days.

Example 9

The hernia patch is generally repaired by adopting a tension-free hernia patch, the hernia patch needs to be fixed after being implanted into a human body, the suture or the titanium nail is adopted for fixing, the pain of a patient can be caused by the suture or the titanium nail, and the pain of the patient can be effectively reduced, and the operation time and the healing time can be shortened by applying the degradable hydrogel in the body and fixing the hernia patch. The preparation method of the hydrogel for repairing hernia comprises the following steps: 0.6 g (2%, w/v) of plasma-derived human serum albumin was weighed and dissolved in 2ml of phosphate buffer (10mM, pH 9.0) prepared in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. The recombinant human serum albumin is irradiated by electron beams, and the irradiation dose is 25 kGy.

0.45g of pentaerythritol polyglycol ether tetrasuccinimide sebacic acid (4-arm-PEG-SSeb, MW 12000D, FIG. 6) was weighed, dissolved in 2ml of phosphate buffer (10mM, pH 7.0) in deionized water, and vortexed to dissolve it as a clear liquid.

And respectively filling the irradiated human serum albumin solution from the plasma source and the pentaerythritol polyglycol ether tetrasuccinimide sebacic acid solution into a two-component injector, and performing cross-linking after spraying to form serum albumin gel. The gel time of the serum albumin solution from the plasma source and the pentaerythritol polyglycol ether tetrasuccinimide sebacic acid solution after mixing is 18 seconds, the swelling rate of the prepared serum albumin gel is 80 percent, the breaking strength reaches 415mmHg, and the in vitro degradation time is 29 days.

Example 10

The existing intestinal anastomosis methods are not complete enough, and the needle hole at the anastomosis part has the risk of leakage. The preparation method of the hydrogel for the intestinal anastomosis operation comprises the following steps:

0.6 g (2%, w/v) of plasma-derived human serum albumin was weighed and dissolved in 2ml of phosphate buffer (10mM, pH 9.0) prepared in deionized water. Stirring intermittently at 37 deg.C for 1 hr to dissolve protein, and evacuating with vacuum pump for 30 min to eliminate bubbles in the solution. Irradiating the human serum albumin solution from the blood plasma by electron beams, wherein the irradiation dose is 25 kGy.

0.4g of pentaerythritol polyglycol ether tetrasuccinimide sebacic acid (4-arm-PEG-SSeb, molecular weight 12000D) was weighed, dissolved in 2ml of phosphate buffer (10mM, pH 7.0) made of deionized water, and vortexed to dissolve it as a clear liquid.

And respectively filling the irradiated human serum albumin solution from the plasma source and pentaerythritol polyglycol ether tetrasuccinimide sebacic acid into a two-component injector, and performing cross-linking after spraying to form serum albumin gel. The gel time of the serum albumin solution from the plasma source and the pentaerythritol polyglycol ether tetrasuccinimide sebacic acid solution after mixing is 20 seconds, the swelling rate of the prepared serum albumin gel is 108 percent, the breaking strength reaches 400mmHg, and the in vitro degradation time is 23 days.

Claims

1. A serum albumin medical product comprises the following components:

(1) a first liquid component comprising 5-45% by mass volume serum albumin dissolved in a buffer at a pH in the range of 6.0-10.0; wherein the serum albumin solution is pre-treated by irradiation with the irradiation dose range of 5kGy-45 kGy;

(2) a second solid component, wherein the solid component is a hydrophilic polymer containing electrophilic functional groups, and the hydrophilic polymer is selected from polyethylene glycol, polyethylene oxide or polyvinyl alcohol; wherein the mass ratio of the solid component to the serum albumin in the first liquid component is 0.3-2; wherein the electrophilic functional group is selected from maleimide group (-Mal), propionaldehyde group (-ALD), succinimidyl carbonate group (-SC), succinimidyl acetate group (-SCM), succinimidyl propionate group (-SPA), succinimidyl succinate group (-SS), succinimidyl glutarate group, succinimidyl sebacate group, succinimidyl group (-NHS), and the number of the functional group is more than 1.

2. The product of claim 1, wherein: when the serum albumin medical product is used, the hydrophilic polymer containing the electrophilic functional groups in the second solid component is dissolved by using a buffer solution with the pH range of 6.0-10.0 to prepare a hydrophilic polymer component solution containing the electrophilic functional groups with the mass volume percentage concentration of 5-45%; the first liquid component is then mixed with a solution of a hydrophilic polymer component containing electrophilic functional groups and crosslinked to form a serum albumin gel.

3. The product of claim 2, wherein: the volume ratio of the serum albumin solution to the polymer solution containing the electrophilic functional groups is 30:70 to 70: 30.

4. The product of claim 3, wherein: the volume ratio of the serum albumin solution to the polymer solution containing the electrophilic functional groups is 40:60 to 60: 40.

5. The product of claim 4, wherein: the volume ratio of the serum albumin solution to the polymer solution containing the electrophilic functional groups is 45:55 to 55: 45.

6. The product of claim 1, wherein: the source of the serum albumin is human, bovine, equine, ovine or mouse serum albumin.

7. The product of claim 6, wherein: the serum albumin is human serum albumin.

8. The product of claim 1, wherein: the serum albumin is produced by genetic engineering recombinant expression, or extracted from human or animal blood plasma.

9. The product of claim 1, wherein: the buffer for dissolving serum albumin in the first liquid component is any buffer capable of maintaining a pH value of 6.0 to 10.0 in an aqueous solution state, and is optionally selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffers.

10. The product of claim 9, wherein: the buffer solution is phosphate buffer solution.

11. The product of claim 9, wherein: the pH value of the buffer solution is 7.0-9.0.

12. The product of claim 9, wherein: the concentration range of the buffer solution is 1-500 mM.

13. The product of claim 12, wherein: the concentration range of the buffer solution is 10-300 mM.

14. The product of claim 13, wherein: the concentration range of the buffer solution is 50-200 mM.

15. The product of claim 14, wherein: the mass volume percentage concentration of the dissolved serum albumin in the first liquid component is 10-40%.

16. The product of claim 15, wherein: the mass volume percentage concentration of the dissolved serum albumin in the first liquid component is 20-30%.

17. The product of claim 1, wherein: in the first liquid component, the serum albumin solution is pre-treated by irradiation with a dose in the range of 10kGy to 40 kGy.

18. The product of claim 17, wherein: in the first liquid component, the serum albumin solution is pre-treated by irradiation with a dose in the range of 20kGy to 35 kGy.

19. The product of claim 17, wherein: the irradiation mode is electron beam irradiation or gamma ray irradiation.

20. The product of claim 19, wherein: the irradiation mode is high-energy ray irradiation generated by an X-ray, cobalt 60, electrostatic accelerator or high-power electron linear accelerator irradiation source.

21. The product of claim 1, wherein: the mass ratio of the second solid component to the serum albumin in the first liquid component is 0.5-1.5.

22. The product of claim 21, wherein: the mass ratio of the second solid component to the serum albumin in the first liquid component is 0.75-1.

23. The product of claim 1, wherein: in the hydrophilic polymer, the number of the functional groups is 2 or 4.

24. The product of claim 1, wherein: the hydrophilic polymer is a succinimide end-capped or succinimide succinate end-capped hydrophilic polymer, and the number of electrophilic functional groups per molecule is more than 2.

25. The product of claim 1, wherein: the main body of the hydrophilic polymer is polyethylene glycol.

26. The product of claim 1, wherein: the molecular weight of the hydrophilic polymer is 1000-100000.

27. The product of claim 26, wherein: the molecular weight of the hydrophilic polymer is 2000-50000.

28. The product of claim 27, wherein: the molecular weight of the hydrophilic polymer is 3000-20000.

29. The product of claim 1, wherein: the hydrophilic polymer containing the electrophilic functional groups is selected from one or more of bis-succinimide propionate-based polyethylene glycol, bis-succinimide succinate-based polyethylene glycol, bis-succinimide glutarate-based polyethylene glycol, bis-succinimide sebacate-based polyethylene glycol, pentaerythritol polyglycol ether tetrasuccinimide glutaric acid, pentaerythritol polyglycol ether tetrasuccinimide succinic acid, pentaerythritol polyglycol ether tetrasuccinimide sebacic acid, and the molecular weight is 1000-100000.

30. The product of claim 29, wherein: the molecular weight of the hydrophilic polymer containing electrophilic functional groups is 2000-50000.

31. The product of claim 30, wherein: the molecular weight of the hydrophilic polymer containing electrophilic functional groups is 3000-20000.

32. The product of claim 29, wherein: the hydrophilic polymer containing the electrophilic functional groups is bis-succinimide succinic ester polyethylene glycol, and the molecular weight is 1000-100000.

33. The product of claim 32, wherein: the molecular weight of the bis-succinimide succinic ester polyethylene glycol is 2000-50000.

34. The product of claim 32, wherein: the molecular weight of the bis-succinimide succinic ester polyethylene glycol is 3000-20000.

35. The product of claim 2, wherein: the buffer used to dissolve the second solid component is any buffer capable of maintaining a pH of 6.0 to 10.0 in an aqueous solution, optionally selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination of the above buffers.

36. The product of claim 35, wherein: the buffer solution is phosphate buffer solution.

37. The product of claim 36, wherein: the pH value of the buffer solution is 6.0-8.0.

38. The product of claim 35, wherein: the concentration range of the buffer solution is 1-500 mM.

39. The product of claim 38, wherein: the concentration range of the buffer solution is 10-300 mM.

40. The product of claim 39, wherein: the concentration range of the buffer solution is 50-200 mM.

41. A medical device kit for delivering a serum albumin medical gel, comprising:

(1) a first liquid component in a sealed first container, the liquid component comprising serum albumin at a concentration of 5% -45% by volume in a buffer solution having a pH in the range of 6.0-10.0; wherein the serum albumin solution is pre-treated by irradiation with the irradiation dose range of 5kGy-45 kGy;

(2) a second solid component in a sealed second container, said solid component being a hydrophilic polymer containing electrophilic functional groups, said hydrophilic polymer being selected from the group consisting of polyethylene glycol, polyethylene oxide or polyvinyl alcohol; wherein the mass ratio of the solid component to the serum albumin in the first liquid component is 0.3-2; wherein the electrophilic functional groups are selected from maleimide group (-Mal), propionaldehyde group (-ALD), succinimidyl carbonate group (-SC), succinimidyl acetate group (-SCM), succinimidyl propionate group (-SPA), succinimidyl succinate group (-SS), succinimidyl glutarate group, succinimidyl sebacate group, succinimidyl group (-NHS), and the number of the functional groups is more than 1;

42. The kit of claim 41, wherein: the source of serum albumin in the first liquid component of the kit is human, bovine, equine, ovine or murine serum albumin.

43. The kit of claim 42, wherein: the serum albumin in the first liquid component of the kit is human serum albumin.

44. The kit of claim 41, wherein: the serum albumin in the first liquid component of the kit is produced by genetic engineering recombinant expression or is extracted from human or animal plasma.

45. The kit of claim 41, wherein: the buffer in the first liquid component of the kit is any buffer capable of maintaining a pH of 6.0-10.0 in an aqueous solution, optionally selected from the group consisting of phosphate buffer, borate buffer, histidine buffer, sodium bicarbonate-sodium carbonate buffer, Tris-HCl buffer, diethanolamine buffer, and combinations thereof.

46. The kit of claim 45, wherein: the buffer in the first liquid component of the kit is a phosphate buffer.

47. The kit of claim 45, wherein: the pH value of the buffer solution in the first liquid component of the kit is 7.0-9.0.

48. The kit of claim 45, wherein: the concentration of the buffer in the first liquid component of the kit is in the range of 1-500 mM.

49. The kit of claim 48, wherein: the concentration of the buffer in the first liquid component of the kit is in the range of 10-300 mM.

50. The kit of claim 49, wherein: the concentration of the buffer in the first liquid component of the kit is in the range of 50-200 mM.

51. The kit of claim 41, wherein: the mass volume percentage concentration of serum albumin in the first liquid component of the kit is 10-40%.

52. The kit of claim 51, wherein: the mass volume percentage concentration of serum albumin in the first liquid component of the kit is 20-30%.

53. The kit of claim 41, wherein: the first liquid component of the kit is pre-treated by irradiation with a dose in the range of 10kGy to 40 kGy.

54. The kit of claim 53, wherein: the first liquid component of the kit is pre-treated by irradiation at a dose in the range of 20kGy to 35 kGy.

55. The kit of claim 41, wherein: the first liquid component of the kit is pre-treated by irradiation, which is electron beam irradiation or gamma ray irradiation.

56. The kit of claim 55, wherein: the first liquid component of the kit is pre-treated by irradiation, wherein the irradiation is performed by high-energy rays generated by an X-ray, cobalt 60, electrostatic accelerator or high-power electron linear accelerator irradiation source.

57. The kit of claim 41, wherein: the mass ratio of the hydrophilic polymer component containing electrophilic functional groups in the second solid component of the kit to the serum albumin in the first liquid component is 0.5-1.5.

58. The kit of claim 57, wherein: the mass ratio of the hydrophilic polymer component containing electrophilic functional groups in the second solid component of the kit to the serum albumin in the first liquid component is 0.75-1.

59. The kit of claim 41, wherein: in the second solid component of the kit, the number of electrophilic functional groups of the hydrophilic polymer is 2 or 4.

60. The kit of claim 41, wherein: in the second solid component of the kit, the hydrophilic polymer is a succinimide-terminated or succinimide succinate-terminated hydrophilic polymer, and the number of electrophilic functional groups per molecule is more than 2.

61. The kit of claim 41, wherein: in the second solid component of the kit, the main body of the hydrophilic polymer is polyethylene glycol.

62. The kit of claim 41, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 1000-100000.

63. The kit of claim 62, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 2000-50000.

64. The kit of claim 63, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 3000-20000.

65. The kit of claim 41, wherein: in the second solid component of the kit, the hydrophilic polymer containing electrophilic functional groups is selected from one or more of bis-succinimide-propionate-based polyethylene glycol, bis-succinimide-succinate-based polyethylene glycol, bis-succinimide-glutarate-based polyethylene glycol, bis-succinimide-sebacate-based polyethylene glycol, pentaerythritol polyethylene glycol ether tetrasuccinimide glutaric acid, pentaerythritol polyethylene glycol ether tetrasuccinimide succinic acid, and pentaerythritol polyethylene glycol ether tetrasuccinimide sebacic acid, and the molecular weight is 1000-100000.

66. The kit of claim 65, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 2000-50000.

67. The kit of claim 66, wherein: in the second solid component of the kit, the molecular weight of the hydrophilic polymer is 3000-20000.

68. The kit of claim 65, wherein: in the second solid component of the kit, the hydrophilic polymer containing the electrophilic functional group is bis-succinimide succinate polyethylene glycol with the molecular weight of 1000-100000.

69. The kit according to claim 68, wherein: the molecular weight of the bis-succinimidyl succinate polyethylene glycol in the second solid component of the kit is 2000-50000.

70. The kit of claim 69, wherein: the molecular weight of the bis-succinimide succinate polyethylene glycol in the second solid component of the kit is 3000-20000.

71. The kit of claim 41, wherein: the buffer in the kit is any buffer capable of maintaining a pH of 6.0-10.0 in an aqueous solution, optionally selected from a phosphate buffer, a borate buffer, a histidine buffer, a sodium bicarbonate-sodium carbonate buffer, a Tris-HCl buffer, a diethanolamine buffer, or a combination thereof.

72. The kit of claim 71, wherein: the buffer solution in the kit is phosphate buffer solution.

73. The kit of claim 71, wherein: the pH value of the buffer solution in the kit is 6.0-8.0.

74. The kit of claim 73, wherein: the concentration of buffer in the kit ranges from 1 to 500 mM.

75. The kit according to claim 74, wherein: the concentration of buffer in the kit ranges from 10 to 300 mM.

76. The kit of claim 75, wherein: the concentration of buffer in the kit ranges from 50 to 200 mM.

77. Use of the serum albumin medical product of any one of claims 1 to 40 or the medical device kit of any one of claims 41 to 76 for the preparation of an adhesive, hemostatic, anti-leakage or anti-adhesion medical device for wounds in various surgical procedures on the human body.

78. The use according to claim 77, wherein: the various surgical operations of the human body are cardiovascular, general surgery, orthopedics, neurosurgery, ophthalmology or orthopedic operations.

79. The use according to claim 78, wherein: the application is the application of preparing a sealed medical appliance for repairing a dura mater in neurosurgery, preparing a sealed medical appliance for reconstructing a blood vessel in cardiovascular surgery, preparing a medical appliance for reducing gas leakage after the fiber suture of lung tissues in the lung resection operation of thoracic surgery, preparing a sealed medical appliance for lens perforation, eyelid operation, lacrimal gland and conjunctiva repair in ophthalmology, and preparing a sealed medical appliance for preventing postoperative adhesion, fixing hernia patches or sealing an anastomotic stoma after intestinal anastomosis operation in surgery.

80. Use of the serum albumin medical product of any one of claims 1 to 40 or the medical device kit of any one of claims 41 to 76 for the manufacture of a medical device for wound closure following pulmonary surgery.