CN1114728C - Staltic fibre and its manufacture method - Google Patents

Abstract

The present invention relates to a medical stanch fiber which is characterized in that the formulation (by weight percentage) comprises 91 to 99% of gelatin and 1 to 9% of polyvinylpyrrolidone. A method for preparing the medical stanch fiber is characterized in that spinning solution is prepared according to the formulation, spinning is carried out by a centrifugal method after the solution is filtred and deaerated; the obtained fiber is directly collected, packaged and sterilized after rapidly desiccated and shaped, and the medical stanch fiber is formed. The spinning process has the following parameters: 40 to 65 DEG C of the solution temperature, 60 to 300 grams per minute of the pumping speed, 4000 to 8000 meters per minute of the linear speed of centrifugal discs, 180 to 280 DEG C of the spinning temperature, and 10 to 40 seconds of the desiccating and shaping time. The present invention of which the average fiber fineness is 1.5 micrometers has the advantages of soft texture, large specific surface area, no constituent or process that is bad for human bodies, safe medical application and good stanching effect.

Description

Hemostatic fiber and its production method

The invention relates to a medical fiber material and a manufacturing method thereof, in particular to a hemostatic fiber and a manufacturing method thereof. Its IPC main classification number is proposed to be D06M15/327.

Hemostatic fiber is a medical fiber material. Since the surface area of the fiber material is much larger than that of general medical films, sponges, etc., it can expand its contact area with the blood on the bleeding wound, making it easier for platelets to adhere or adsorb on the surface of the fiber, which is conducive to the coagulation of blood on the bleeding wound. To achieve the purpose of rapid hemostasis. According to retrieval, most of the existing hemostatic fibers are manufactured with gelatin as the main component, and the process methods are also different. For example, Chinese patent CN85109219A discloses a technology for manufacturing hemostatic fibers by using a dry spinning process instead of a wet spinning process. The content of gelatin/polyvinyl alcohol (40-65/35-60) in its hemostatic fiber is 40-50%, and the rest is mainly soft water; and as Chinese patent CN1157355A discloses a kind of " composition of hemostatic fiber and its gas drafting method spinning process". The gelatin content in the hemostatic fiber is increased to 70-90%, and the rest is also polyvinyl alcohol (10-30%) or a small amount of other additives. Gelatin is a protein that is easily absorbed by the human body and is harmless for medical use. Therefore, people always hope to increase the proportion of gelatin in the hemostatic fiber to improve the medical effect of the hemostatic fiber. But high proportion even pure gelatin hemostatic fiber has poor spinning and fiber-forming performance, so the prior art always has to add a considerable amount of polyvinyl alcohol to improve its spinning and fiber-forming performance. However, polyvinyl alcohol is a polymer compound that is not easily absorbed by the human body, and its medical performance is not ideal. More importantly, in the prior art, formaldehyde is used for the corresponding treatment of hemostatic fibers (such as the above two cases), which is obviously unfavorable or harmful to the human body and the environment, and is also expressly prohibited by advanced technology standards. It can be said that this is the main crux of the fact that the existing hemostatic fibers cannot be practically applied and widely promoted. In addition, the process of the prior art of hemostatic fiber is relatively complicated, with many procedures, long cycle, low efficiency, and no obvious technical advantages.

The object of the present invention is to provide a hemostatic fiber with high gelatin content, no additives that cannot be absorbed by the human body and its efficient and safe manufacturing method, and the method has good spinning and fiber-forming performance, without any possible harm to the human body or the environment process with harmful effects.

The object of the present invention is achieved as follows: design a kind of hemostatic fiber with gelatin as the main component, it is characterized in that the weight percent formula of this hemostatic fiber miscible component is:

Gelatin 91～99%;

Polyvinylpyrrolidone 1-9%.

A manufacturing method suitable for producing the hemostatic fibers described above was devised. It is characterized in that the spinning stock solution is made according to the above-mentioned formula, and after being stirred and miscible, filtered and defoamed, it is spun by centrifugal method, and the obtained fiber is quickly dried and formed, and directly collected, packaged and sterilized, that is, the described The hemostatic fiber; The described centrifugal spinning process parameter is:

Spinning dope temperature 40～65℃;

Pump feed liquid speed 60～300 g/min;

Linear speed of centrifugal disc 4000～8000 m/min;

Spinning temperature 180～280℃;

The time for the rapid drying and molding of the fibers is 10-40 seconds.

The gelatin content of the hemostatic fiber of the present invention can be as high as 91-99%, or even higher, greatly exceeding the level of the prior art. The product of the present invention completely abandons the additive in the hemostatic fiber of the prior art—polyvinyl alcohol, and adopts polyvinylpyrrolidone as a small amount of additive. Although polyvinylpyrrolidone is also a synthetic water-soluble polymer compound, it has the general properties of water-soluble polymer compounds, such as colloidal protection, film-forming, cohesiveness, hygroscopicity, solubilization or coagulation, etc., but it is different from Compared with polyvinyl alcohol in the prior art, its outstanding performance is its good solubility and biocompatibility, without any adverse stimulation or side effects on sensitive parts of the human body such as skin, mucous membranes, eyes, etc., and does not produce antigenicity to the human body, nor Inhibit the production of human antibodies, safe and reliable for medical use. Polyvinylpyrrolidone has been included in the pharmacopoeia of the United States, Britain, Germany, France, Europe and other countries or regions, and has also been accepted by health agencies around the world. After inspection, the "acute toxicity test (mice)" conclusion of the product of the present invention is "according to the "Chemical Substances Acute Toxicity Measurement and Grading Standard", this product belongs to actual non-toxicity" (Tianjin City Health and Disease Prevention Center, Tianjin Food Hygiene Supervision and Inspection Institute inspection report - NO97-589); "cytotoxicity test" conclusion is "cytotoxicity test qualified" (test report of Tianjin Medical Biomaterials Center - NO980108); "acute skin irritation" test conclusion is " No irritation to the skin of rabbits” (Tianjin City Health and Disease Prevention Center, Tianjin Food Hygiene Supervision and Inspection Institute Inspection Report - NO97-590); the conclusion of the “intradermal irritation test” is also “no irritation to the skin of rabbits” (Tianjin Sanitation and Disease Prevention Center, Tianjin Food Hygiene Supervision and Inspection Institute inspection report——NO97-388); , compared with the negative control group, there is no significant difference, indicating that the skin sensitization test of this sample is qualified." (Tianjin Municipal Health and Disease Prevention Center, Tianjin Food Sanitation Supervision and Inspection Institute Inspection Report-NO98-348).

The hemostatic fiber of the present invention not only does not contain any possible or potential medical safety hazards, firstly, the medical safety performance indicators such as non-toxic and non-irritating are guaranteed, and the functional indicators such as blood absorption and hemostasis are also at a good level. Through inspection, " hemolysis test " inspection conclusion of hemostatic fiber of the present invention is " the dissolution rate of hemostatic fiber dressing is 0%, meets the regulation of ISO＜5%, and hemolysis test is qualified." (Tianjin Medical Biomaterials Center inspection report book—NO980107); the conclusion of "absorbability test" is that "this hemostatic fiber has absorbability in the abdominal cavity" (Tianjin Health and Disease Prevention Center, Tianjin Food Hygiene Supervision and Inspection Institute Inspection Report——NO99-035) The conclusion of the "hemostasis test" is "1. The hemostatic fiber has obvious hemostatic effect. 2. The visceral hemostatic effect of the hemostatic fiber is stronger than that of the traumatic blood vessel, and the absorption is faster, and it is not easy to cause adhesion with other tissues." ( Inspection report of Tianjin Health and Disease Prevention Center and Tianjin Food Hygiene Supervision and Inspection Institute——NO99-034).

The original hemostatic fiber centrifugal spinning process of the present invention not only solves the problems of high gelatin content spinning and poor fiber-forming performance, but also has better performance than the existing hemostatic fiber dry spinning process and gas draft spinning process equipment. Reduced, shortened process, easy control, reduced cost and improved efficiency. In particular, no harmful formaldehyde is used in the whole spinning process of the hemostatic fiber of the present invention, which truly eliminates "three wastes" pollution, ensures medical safety, and is beneficial to the practical application and popularization of the product.

Further describe the present invention below in conjunction with embodiment and accompanying drawing:

Fig. 1 is the process flow diagram of the inventive method;

Fig. 2 is the process flow diagram of the prior art method for comparison.

In the hemostatic fiber formula of the present invention, in addition to increasing the gelatin content that is easily absorbed by the human body (from 70--90% of the prior art to 91-99%) in a relatively large proportion, it is also designed to be added in a small amount, which can be assured The polyvinylpyrrolidone used is to replace polyvinyl alcohol, a synthetic macromolecular compound that is not easily absorbed by the human body in the prior art, so the medical effect and safety performance of the product of the present invention are greatly improved compared with the prior art product.

In order to solve the problem of unsatisfactory spinning and fiber-forming properties with high gelatin content, the invention also creates a centrifugal spinning process. The spinning process is as follows (see Figure 1): after dissolving, mixing, filtering, and defoaming the various formulation raw materials respectively or simultaneously, the spinning stock solution is obtained; The flow rate is pumped into the centrifugal spinning machine and directly spun into short fibers; the obtained short fibers meet the purified hot air during the falling process and are directly dried. Because the fiber of the product obtained by the method of the present invention is very fine, the moisture in the fiber can evaporate rapidly during its falling process, and the fiber is already dry when it falls to the receiver; the dried fiber is directly vacuum-packed, and then sterilized by radiation The hemostatic fiber product of the present invention can be produced efficiently and safely after being sterilized.

Centrifugal spinning process parameter of the present invention is:

Spinning dope temperature 40℃～65℃;

Pump feed liquid speed 60～300 g/min;

Linear speed of centrifugal disc 4000～8000 m/min;

Spinning temperature 180℃～280℃

The time for fiber drying and molding is only 10-40 seconds.

Under the above formula, method and process conditions, spinning can be carried out smoothly. When the speed of the pump feed liquid is 60-200 g/min and the linear speed of the centrifugal disc is controlled at 5000-8000 m/min, the average diameter of the spun hemostatic fiber can reach 1.5 μm (analysis report NO99- 526). Because the hemostatic fiber spun by the invention has a finer diameter, softer texture and increased specific surface area of the fiber, the medical hemostatic effect and the comfort of the wounded surface of the patient can be further improved.

Fig. 2 is the process flow chart of prior art (CN1157355A). Compared with it, it can be clearly seen that the process flow of the present invention (Fig. 1) has removed the necessary compressed air source and its supporting equipment in the gas drawing method spinning process, the equipment is reduced, and there is no energy consumption. The cost is reduced; compared with the long process of traditional wet spinning, the process is greatly shortened; compared with the existing dry spinning process, it also saves the processes of winding, bunching and cutting, so it can be used The product production cycle is shortened, the energy consumption is reduced, the production efficiency is significantly improved, and the cost is greatly reduced.

In order to further improve and enhance the medical performance and effect, a small amount or a small amount of additives that are harmless to the human body and easy to absorb, such as water-soluble chitosan and sodium alginate, can also be added separately or simultaneously in the formula of the present invention. The water-soluble chitosan substance is a chitosan derivative obtained from chitin extracted from crustaceans through carboxylation modification. It has good biocompatibility and biological activity. Through experiments and clinical observations, water-soluble chitosan has good affinity with the cells of organisms; it has great adsorption capacity for blood components such as serum and protein; it has high permeability for middle molecular substances in serum ; The possibility of producing antigens is very small; contact with blood can quickly produce coagulation and form a coagulation layer; it can be decomposed by the action of enzymes in the living body, etc. Adding a small amount of water-soluble chitosan in the formula of the invention can increase the hemostatic effect and human body absorption performance of the hemostatic fiber product. Sodium alginate is a substance extracted from natural seaweed. Sodium alginate has good liquid absorption. The present invention adds a small amount of sodium alginate to make use of its performance to quickly clean the wound surface. Sodium alginate will also form a thick layer of gel to cover the wound, further improving its hemostatic function, and at the same time avoiding the adhesion of the hemostatic fiber compress to the wound (see the conclusions of the above-mentioned relevant test reports).

A further feature of the present invention is to increase the additive on the basis of the main formula (i.e. the aforementioned formula, or formula 1), and the specific formula is:

Formula 2: Gelatin 92～98.5%;

    Polyvinylpyrrolidone   1～5%;

  Water-soluble chitosan 0.5-3%.

Formula 3: Gelatin 94.5～98.99%;

Sodium alginate 0.01～0.5%;

  Polyvinylpyrrolidone 1-5%.

Formula 4: Gelatin 91.5～98.49%;

    Polyvinylpyrrolidone   1～5%;

 Water-soluble chitosan 0.5～3%;

Sodium alginate 0.01～0.5%

No matter that kind of formula of the present invention, used gelatin is medical grade gelatin. However, medical gelatin with different molecular weights has certain influence on spinning performance and fiber-forming effect. Through experimental research, the molecular weight of the medical gelatin selected by the present invention is 100,000 to 130,000. Within this range, better products of the present invention can be obtained. Similarly, the sodium alginate and the water-soluble chitosan of the additive of the present invention are also of pharmaceutical grade. Under the above formula and process conditions, the additives have no significant effect on the spinning and fiber forming effects. It should also be noted that although the content of gelatin in the given formula of the present invention can be as high as 99%, it does not exclude the possibility of spinning pure gelatin (99%--100% gelatin) hemostatic fiber with the method of the present invention, or Said, it is entirely possible to spin pure gelatin hemostatic fibers with the method of the present invention. In fact, the inventor has made beneficial attempts in this regard and achieved relatively satisfactory results.

A further feature in the centrifugal spinning process of the present invention is that the obtained hemostatic fiber product adopts the process of packaging first and then sterilizing; the packaging adopts vacuum packaging, and the disinfection adopts cobalt 60 gamma ray irradiation disinfection, and the dose range of the radiation is between 1.4-24,000 grays, the dose rate is 600 grays/hour. On the one hand, this packaging and disinfection method fundamentally eliminates the secondary pollution that may be caused by disinfection first and then packaging, and the product is safer for medical use; on the other hand, the production efficiency can be greatly improved by using cobalt 60 gamma ray disinfection technology. The post-processing method adopted in the prior art (CN1157355A) needs multiple procedures (see Figure 2), and takes a long time. Among them, it takes 4 to 6 hours for drying in a far-infrared drying oven and fumigation with formaldehyde vapor, and it needs to be placed in a balance room for 8 hours before the fibers can be packed into inner packaging bags, sterilized with ethylene oxide, and then Carry out outer packing again, make hemostatic fiber finished product. This method takes too long, consumes too much energy, is very inefficient, and may be unsafe or unhygienic. The process flow of the method of the present invention is simple, the product production cycle is very short, not only one-step fiber formation (that is, centrifugal spinning), but also drying at the same time, only takes 10-40 seconds, the efficiency is very high, the cost is greatly reduced, and the first direct collection and packaging , post-irradiation sterilization and disinfection, there is absolutely no chance and possibility of secondary pollution, and the medical safety is assured. The conclusion of the "sterility test" test proves that "the ultrafine hemostatic fibers irradiated by three different doses (160, 180, 230 rads) have no bacterial growth" (Tianjin Health and Disease Prevention Center, Tianjin Food Hygiene Supervision Laboratory inspection report - NO99-033).

It should also be pointed out that the present invention not only does not use polyvinyl alcohol, a synthetic high molecular compound that is not easily absorbed by the human body, in the formula components, but also does not use the formaldehyde used in the prior art in the spinning process, thereby absolutely avoiding The obvious and potential damage or pollution that formaldehyde, which is harmful to human body and environment, may bring. Therefore, the present invention does not have any possible pollution no matter from the content of the formula components or from the process of the process, and it really does not have the problem of "three wastes" treatment. The production is very safe and the medical use is very safe. It can be called "green hemostatic fiber” or “green product”.

Specific examples of the present invention are given below.

Example 1:

Put 237.5g of pharmaceutical grade gelatin with a molecular weight of 130,000 into 700g of distilled water and swell for 150 minutes at room temperature; put 12.5g of polyvinylpyrrolidone into 300g of distilled water and dissolve at 40°C; In the swollen gelatin, heat up to 75°C, stir and mix for 90 minutes, and then filter the mixture; pump the filtered mixture into the high-level tank; stand at 60°C for 4 hours, and then put the mixture Open the valve when the temperature is controlled at 60°C; the mixed material liquid enters the centrifugal spinning machine through the metering pump, the pump supply or speed is 150g/min, the centrifugal disc line speed is 6000 m/min, and the material liquid is quickly spun into short fibers; During the falling process of the wet short fiber, it fully meets the hot air in the spinning box with a spinning temperature of 250°C, and quickly evaporates the moisture in the fiber; when the fiber falls to the receiver (about 15 seconds), it has already dry. After the fibers are vacuum-packed, they are sterilized under the irradiation of cobalt 60 gamma rays with a dose of 18,000 Gy at a dose rate of 600 Gy/h to produce the finished hemostatic fiber of the present invention.

Example 2:

Put 247.5 pharmaceutical grade gelatin with a molecular weight of 100,000 into 800g of distilled water, and swell at room temperature for 150 minutes; put 2.5g of polyvinylpyrrolidone into 200g of distilled water, and dissolve it at 40°C; In the final gelatin, heat up to 75°C, stir and miscible for 90 minutes; then filter the mixture, and stand at 60°C for defoaming for 4 hours; after controlling the temperature of the material at 45°C, open the valve, and the mixture liquid passes through the metering The pump enters the centrifugal spinning machine. The post-processing of spinning and fiber is basically the same as that of Example 1, wherein the pump supply rate is adjusted to 70 g/min, the line speed of the centrifugal disc is adjusted to 4500 m/min, and the spinning temperature is adjusted to 190°C.

Example 3:

Put 241.5g of pharmaceutical grade gelatin with a molecular weight of 110,000 into 500g of distilled water and swell for 150 minutes at room temperature, put 7.2g of polyvinylpyrrolidone into 200g of distilled water, and put 1.3g of commercially available carboxylated chitosan sodium salt into 300g of distilled water Dissolve in 50°C; put the dissolved feed liquid into the swollen gelatin, heat up to 75°C and stir for 90 minutes to mix. Then filter the mixed material, pump the filtered feed liquid into the high-level tank, let stand at 60°C for degassing for 4 hours, control the feed temperature at 55°C, open the valve feed liquid and enter the centrifugal spinning machine through the metering pump, The pump supply rate is 300G/min, the centrifugal disc line speed is 7600m/min, and the feed liquid is rapidly spun into short fibers. The wet short fiber meets the hot air in the spinning box, the spinning temperature is 280°C, the moisture in the fiber is evaporated quickly, and the fiber is dry when it falls to the receiver (about 35 seconds). After the fibers are vacuum-packed, they are sterilized under cobalt-60γ-ray irradiation at a dose of 16,000 Gy at a dose rate of 600 Gy/h to make finished hemostatic fibers.

Example 4:

Put 238g of pharmaceutical grade gelatin with a molecular weight of 110,000 into 500g of distilled water, and swell at room temperature for 150 minutes; put 4.5g of polyvinylpyrrolidone into 200g of distilled water, and put 7.5g of commercially available carboxylated chitosan sodium salt into 300g of distilled water Dissolve at 50°C; put the dissolved feed solutions into the swollen gelatin to make spinning dope. The spinning and fiber post-treatment processes are the same as in Example 1.

Example 5:

Put 212.67g of pharmaceutical grade gelatin with a molecular weight of 120,000 into 500g of distilled water, and swell at room temperature for 150 minutes; put 7.3g of polyvinylpyrrolidone into 200g of distilled water, and 0.03g of pharmaceutical grade water-soluble sodium alginate into 300g of distilled water , dissolved at 50°C; put the dissolved feed solutions into the swollen gelatin, raise the temperature to 75°C, and stir for 90 minutes to mix. Then, the mixed material liquid was filtered, and the filtered mixed material liquid was pumped into a high-level tank, and stood at 60° C. for 4 hours for defoaming. The spinning and fiber post-treatment processes are the same as in Example 1.

Embodiment 6:

Put 214.6g of pharmaceutical grade gelatin with a molecular weight of 110,000 into 500g of distilled water, and swell at room temperature for 150 minutes; put 4.4g of polyvinylpyrrolidone into 100g of distilled water, and 1.0g of pharmaceutical grade water-soluble sodium alginate into 400g of distilled water , Dissolved at 50°C; put the dissolved feed solutions into the swollen gelatin to make spinning dope. The spinning and fiber post-treatment processes are the same as in Example 1.

Embodiment 7:

Put 210.76g of pharmaceutical grade gelatin with a molecular weight of 110,000 into 400g of distilled water, and swell at room temperature for 150 minutes; put 4.4g of polyvinylpyrrolidone into 100g of distilled water, and put 4.4g of commercially available carboxylated chitosan sodium salt into 200g In distilled water, put 0.44g of pharmaceutical grade water-soluble sodium alginate into 300g of distilled water and dissolve at 50°C; put the dissolved feed solutions into swollen gelatin to make spinning stock solution. The spinning and fiber post-treatment processes are the same as in Example 1.

Claims (10)

1. one kind is the stanch fibre of main component with the gelatin, it is characterized in that the percentage by weight prescription of the miscible component of this stanch fibre is:

Gelatin 91～99%;

Polyvinylpyrrolidone 1～9%.

2. stanch fibre according to claim 1 is characterized in that the percentage by weight prescription of the miscible component of this stanch fibre is:

Gelatin 92～98.5%;

Polyvinylpyrrolidone 1～5%;

Water soluble chitosan 0.5～3%.

3. stanch fibre according to claim 1 is characterized in that the percentage by weight prescription of the miscible component of this stanch fibre is:

Gelatin 94.5～98.99%;

Polyvinylpyrrolidone 1～5%;

Sodium alginate 0.01～0.5%.

4. stanch fibre according to claim 1 is characterized in that the percentage by weight prescription of the miscible component of this stanch fibre is:

Gelatin 91.5～98.49%;

Polyvinylpyrrolidone 1～5%;

Water soluble chitosan 0.5～3%;

Sodium alginate 0.01～0.5%.

5. according to claim 1,2,3 or 4 described stanch fibres, it is characterized in that used gelatine molecular weight is 10～130,000 medical gelatin.

6. a manufacture method that is applicable to production claim 1,2,3 or 4 described stanch fibres is characterized in that making spinning solution by described prescription, after, filtration miscible through stirring, the deaeration, adopts the centrifugal process spinning; The rapid drying and moulding of gained fiber, and directly collect, pack, sterilize, promptly make described stanch fibre;

Described centrifugal process spinning technology parameter is:

40～65 ℃ of spinning solution temperature;

Pump feed liquid speed 60～300 gram/minute;

4000～8000 meters/minute of centrifugal pan linear velocities;

180～280 ℃ of spinning temperatures;

The rapid drying and moulding time of described fiber is 10～40 seconds.

7. a manufacture method that is applicable to the described stanch fibre of production claim 5 is characterized in that making spinning solution by described prescription, after, filtration miscible through stirring, the deaeration, adopts the centrifugal process spinning; The rapid drying and moulding of gained fiber, and directly collect, pack, sterilize, promptly make described stanch fibre;

Described centrifugal process spinning technology parameter is:

40～65 ℃ of spinning solution temperature;

Pump feed liquid speed 60～300 gram/minute;

4000～8000 meters/minute of centrifugal pan linear velocities;

180～280 ℃ of spinning temperatures;

The rapid drying and moulding time of described fiber is 10～40 seconds.

8. according to the manufacture method of the described stanch fibre of claim 6, it is characterized in that the mid diameter with the prepared stanch fibre of this method is 1.5 μ m.

9. according to the manufacture method of the described stanch fibre of claim 7, it is characterized in that the mid diameter with the prepared stanch fibre of this method is 1.5 μ m.

10. according to Claim 8, the manufacture method of 9 described stanch fibres, it is characterized in that gained stanch fibre product adopts packing earlier, the process of back sterilization; Described packing adopts vacuum-packed, and the sterilization of cobalt 60 gamma-rays is adopted in described sterilization, and the dosage range of ray is at 1.4～2.4 Wan Gerui.

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