CN108939139B

CN108939139B - Preparation method of medical adhesive with efficient anti-inflammatory and hemostatic functions

Info

Publication number: CN108939139B
Application number: CN201810881120.5A
Authority: CN
Inventors: 叶善明; 林闪光; 应磊
Original assignee: Zhejiang Paifeite New Material Technology Co ltd
Current assignee: Zhejiang Paifeite New Material Technology Co ltd
Priority date: 2018-08-04
Filing date: 2018-08-04
Publication date: 2021-02-02
Anticipated expiration: 2038-08-04
Also published as: CN108939139A

Abstract

The invention discloses a preparation method of medical adhesive with efficient anti-inflammatory and hemostatic functions, which is characterized by comprising the following components in parts by weight: 20-25 parts of a-n-octyl cyanoacrylate, 25-35 parts of a-isooctyl cyanoacrylate, 2-6 parts of polyvinyl acetate, 12-20 parts of efficient anti-inflammatory component, 13-23 parts of efficient hemostatic component, MG-603-6 parts of cell activator, 8-10 parts of allantoin, 1 part of hydrolyzed wheat protein, 1 part of stabilizer, 150-220 parts of composite anti-inflammatory fruit oil component and 200 parts of sterile water. The medical adhesive of the invention particularly selects various extracts with anti-inflammatory and hemostatic functions, adds two high-efficiency anti-inflammatory components and one high-efficiency hemostatic component to improve the overall anti-inflammatory and hemostatic effects, has high bonding strength and short hemostatic time, and meets the clinical application requirements on medical adhesives.

Description

Preparation method of medical adhesive with efficient anti-inflammatory and hemostatic functions

Technical Field

The invention belongs to the technical field of medical materials, and particularly relates to a preparation method of medical glue with efficient anti-inflammatory and hemostatic functions.

Background

With medical advances, clinical requirements for surgical techniques and the effects of auxiliary materials are becoming higher and higher. The requirement of modern medicine is to minimize the pain of the patient and to ensure the life of the patient, so that the rapid hemostasis and anti-inflammation during the operation is particularly important. The medical adhesive is a branch of medical macromolecules, takes biological tissues as an adhesive object, and can replace partial suture and ligation operations by applying an adhesive technology to most tissues and organs of a human body in the treatment process without anesthesia; the wound is automatically dropped after healing. Compared with the traditional method, the use of the medical adhesive can effectively shorten the operation time, reduce the pain of a patient, realize quick hemostasis and anti-inflammation, quickly repair wounds and ensure the attractiveness.

The main research direction of the medical adhesive at present is to improve the bonding strength of various adhesives, however, the biomedical materials applied in the surgical operation at present rarely have the functions of high-efficiency anti-inflammation and large-area wound hemostasis. In the operation, firstly, the hemostasis is quickly completed, so that the medicine can be better transmitted; patients with good anti-inflammatory effects will enter the recovery state more safely and earlier. The generation of formaldehyde in the storage and use processes of cyanoacrylate medical adhesive has side effects on organism tissues, and the damage to organisms is increased along with the increase of the concentration of the formaldehyde, thereby seriously influencing the effect and the application of the medical adhesive.

Disclosure of Invention

Based on the prior art, the invention aims to provide the medical adhesive which combines a plurality of effective components to greatly improve the hemostasis rate and the anti-inflammatory effect and effectively inhibit the generation of formaldehyde and has the efficient anti-inflammatory and hemostasis functions and the preparation method thereof.

The purpose of the invention is realized by the following technical scheme:

the medical adhesive with the efficient anti-inflammatory and hemostatic functions is characterized by comprising the following components in parts by weight: 20-25 parts of a-n-octyl cyanoacrylate, 25-35 parts of a-isooctyl cyanoacrylate, 2-6 parts of polyvinyl acetate, 12-20 parts of efficient anti-inflammatory component, 13-23 parts of efficient hemostatic component, MG-603-6 parts of cell activator, 8-10 parts of allantoin, 1 part of hydrolyzed wheat protein, 1 part of stabilizer, 150 parts of composite anti-inflammatory fruit oil component, 220 parts of sterile water and 200 parts of sterile water;

the efficient anti-inflammatory component comprises 2 parts of abalone anti-inflammatory peptide, 3 parts of Yunnan pine moth pupa chitin, 6 parts of figwort polysaccharide and 5 parts of shinyleaf yellowhorn extract by weight;

the efficient hemostatic components comprise 5 parts of garden burnet root extract, 3 parts of Sinkiang arnebia root extract, 3 parts of buttercup extract, 6 parts of lotus rhizome node carbon extract and 6 parts of sophora flower charcoal extract by weight;

the composite anti-inflammatory fruit oil component comprises, by weight, 4 parts of kiwi fruit seed oil, 3 parts of mei teng fruit oil, 2 parts of eucommia seed oil and 5 parts of schisandra fruit oil.

Further, the stabilizer is prepared from polyanionic cellulose and 2, 6-di-tert-butyl-4-methylphenol according to the weight part of 10: 1 are combined.

Further, the sanguisorba officinalis extract in the high-efficiency hemostasis component is a sanguisorba officinalis ethyl acetate extract; the Sinkiang arnebia root extract is an ethyl acetate extract of Sinkiang arnebia root; the lotus rhizome node charcoal extract is an ethyl acetate extract of lotus rhizome node charcoal; the sophora japonica charred extract is an ethyl acetate extract of sophora japonica charred, and the ranunculus ternatus extract is an ethanol extract of ranunculus ternatus.

Further, the ranunculus japonicus extract is prepared by taking 80% ethanol water solution as a solvent, leaching in hot water at 70 ℃ for 3h in a water bath at a material-to-liquid ratio of 2:1, standing in the dark for 15h, filtering, performing rotary evaporation concentration to 1.5g/ml, sterilizing the concentrated solution by a microporous filter membrane device, and then performing forced air drying at 500 ℃.

Further, the preparation method of the shinyleaf yellowhorn extract comprises the following steps: washing off silt on the surface of the shinyleaf yellowhorn by using flowing water, introducing an ozone generator into sterile water to wash the shinyleaf yellowhorn again, crushing pulp into pulp, adding deionized water according to the volume of 30% of the pulp, adding 2.5% of pectinase at the same time, stirring uniformly, and standing for 50 min at 33 ℃; adding the supernatant into 90% ethanol solution, ultrasonic extracting at 35 deg.C and 100W ultrasonic power for 20min, and centrifuging at 4000rpm/min for 10 min; after concentrating the supernatant from the centrifugation to a semi-fluid slurry, the slurry was mixed at a ratio of 1: dissolving 12 volume ratio in deionized water, stirring, shaking, and sterilizing with microporous membrane to obtain xanthoceras sorbifolia extract.

Further, the method for extracting the Yunnan pine moth pupa chitin comprises the following specific operations:

(1) deproteinization and lipid; the pupa bombycis pupa is put into a gauze bag, soaked in water for squeezing, then washed, filtered, separated from pupa skin and pupa skin such as protein, and finally the pupa skin is put into sodium hydroxide solution for heating, and after the waste alkali liquor is discarded, washed to be neutral and dried in the sun;

(2) demineralizing; placing the pupa skin which is deproteinized and lipidated in the step 1 in a hydrochloric acid solution for heating treatment, discarding the waste acid solution, washing with water to be neutral, and drying in the sun;

(3) decoloring and washing with water; treating the product obtained in the step 2 with hydrogen peroxide, decoloring, washing with water to be neutral, and drying in the sun to obtain chitin;

(4) deacetylation; putting the product obtained in the step 3 into a sodium hydroxide solution for heating, discarding the waste alkali liquor, and washing to be neutral to obtain the Yunnan pine moth pupa chitin;

wherein the mass fraction of the sodium hydroxide solution is 8%, the soaking time is 2h, and the soaking temperature is 80 ℃; the mass fraction of the hydrochloric acid solution is 2.5%, the soaking time is 20h, and the soaking temperature is 30 ℃; the mass fraction of the hydrogen peroxide solution is 11 percent, the soaking time is 2.5h, and the soaking temperature is 80 ℃.

A preparation method of medical glue with efficient anti-inflammatory and hemostatic functions is characterized by comprising the following steps:

step one, adding a cell activating agent MG-60, allantoin, hydrolyzed wheat protein and a stabilizer into sterile water according to a part ratio, heating to 85 ℃, stirring and dissolving for 180min, and cooling to room temperature to obtain an aqueous solution A;

step two, adding the n-octyl a-cyanoacrylate, the isooctyl a-cyanoacrylate and the polyvinyl acetate into the composite anti-inflammatory fruit oil component according to the proportion in parts, heating to 70 ℃, stirring for 80min, and cooling to room temperature to obtain a composite anti-inflammatory fruit oil component solution B;

step three, uniformly mixing the aqueous solution A and the compound anti-inflammatory fruit oil component solution B, adding the efficient anti-inflammatory component and the efficient hemostatic component according to the proportion in parts, and stirring for 4 hours;

and step four, filtering and sterilizing the product obtained in the step three, subpackaging, sealing and packaging to obtain the medical adhesive with efficient anti-inflammatory and hemostatic functions.

The medical alpha-cyanoacrylate glue has developed fast because of its unique advantages of single component, no solvent, no need of added catalyst, etc. and may be adhered fast at normal temperature. Moreover, the adhesive has the characteristics of wide adhesive range, high strength and instant curing, and more importantly, the medical adhesive has no toxic or side effect on organisms such as skin and the like. The particularity of the chemical structure determines the excellent property of the alpha-cyanoacrylate in adhesion, and the alpha-carbon atom in the molecular structure CNCH2CCOOR of the alpha-cyanoacrylate compound has extremely strong ability of attracting electrons, so that the chemical reaction can be immediately carried out when the alpha-cyanoacrylate compound contacts with a very small amount of anions. The basic substance of the organism, namely protein amino acid chains, are provided with a large number of electronegative groups-NH 2 and-COOH, and when the basic substance of the organism is contacted with alpha-cyanoacrylate, the reaction can be rapidly carried out, and the principle also enables the medical adhesive to be widely applied to clinic. The effect of α -cyanoacrylates on tissue is strongly related to the type and size of the alkyl group. Generally, the longer the ester carbon chain, the slower the polymerization reaction rate, the less irritation to the tissue, and the better the flexibility of the adhesive layer. The invention selects the a-n-octyl cyanoacrylate and the a-isooctyl cyanoacrylate as main raw materials in the system, and the a-octyl cyanoacrylate and the isooctyl cyanoacrylate have good biocompatibility and excellent high-efficiency anti-inflammatory hemostatic performance. The needle suture operation is replaced, so that no trace is left after the skin incision is anastomosed. Polyvinyl acetate (also known as polyvinyl acetate). Is a polymer of vinyl acetate (vinyl acetate). Abbreviated english as PVAc. PVAc for short, a polymer produced by polymerizing vinyl acetate. The adhesive is an excellent adhesive, and various comprehensive properties of the adhesive can be effectively improved by adding the adhesive into an alpha-cyanoacrylate matrix.

Chitin is a natural resource which is abundant on the earth, and is the only positively charged animal cellulose found in nature. Because the molecular structure of the material contains unsaturated cationic groups, the material has strong adsorption effect on various harmful substances with negative charges. It can also remove the garbage in human body, and can achieve the purposes of preventing diseases and prolonging life. Because chitin has the unique function, chitin is praised by European and American scientists as the sixth vital element of human body which is as important as protein, fat, carbohydrate, vitamin and mineral substance. Chitin, also known as chitin, a biopolymer of chitosan, is widely found in invertebrate shells and fungal mycelia as well as protozoa and certain green algae. Chitin has effects of resisting cancer, inhibiting metastasis of tumor cells, improving immunity, protecting liver, removing toxic substance, inhibiting microorganism/bacteria/mold, and relieving inflammation and promoting wound healing. The dissolved chitosan is in a gel state and has strong adsorption capacity, and chitin molecules contain polar groups such as hydroxyl, amino and the like, so that the chitosan is strong in hygroscopicity and is also a good moisturizing agent after skin repair. Pine moth is a historic forest pest in China, and Yunnan pine moth is one of 6 big pine moths which are the most serious harm in China. In the research of the recycling of the pine moth, the Yunnan pine moth pupa and the imago contain rich protein and fat, and the content of the chitin is also higher.

Blood coagulation is a series of enzymatic processes, which finally convert fibrinogen into fibrin, the blood is converted from a sol state to a gel state, and thrombin plays an important role in blood coagulation. The platelet plays an important role in the blood coagulation process, plays a role in blood comparison through adhesion, aggregation and release, and provides membrane phospholipid necessary for activation of various prothrombin. The chemical components of arnebia euchroma mainly comprise anthraquinone, phenolic acid, alkaloid, phenol, benzoquinone, triterpenes, sterols, flavonoids, polysaccharides and other substances. The Sinkiang arnebia euchroma ethyl acetate extract has high-efficiency hemostatic effect, and the hemostatic effect is a process of promoting the fibrinogen to be converted into fibrin by increasing the fibrinogen content. The platelet number is increased, the anticoagulation and fibrinolysis system are influenced to play a role, and exogenous and endogenous coagulation factors are not influenced.

Geranium strictipes (Ceruium strictipes. R. Knuth) Geranium strictipes of Geraniaceae is widely distributed in Zhongdian, shuixing, Shuishen, humanity and other areas of Yunnan, with root as medicine and also known as Dingshan Xiao. Has long been used for treating diseases such as enteritis in white nationality and Yi nationality in Yunnan. Researches show that the burnet alcohol extract has obvious antibacterial effect on common intestinal infectious bacteria in vitro, meanwhile, the burnet has strong anti-inflammatory, hemostatic and blood coagulation effects, and the high-dose burnet extract has better hemostatic effect than Yunan self-medicine. The Geranium strictipes extract has the functions of resisting inflammation and quickly stopping bleeding and clotting blood.

Nodus Nelumbinis Rhizomatis is the dry rhizome of Nelumbo Nucifera Gaertn of Nymphaeaceae. It is listed as the superior product in Ben Jing (the book of academic records). Lotus root node charcoal is the fried charcoal product of Lotus root node, and is recorded in the ministry of Chinese pharmacopoeia and national Standard of Chinese medicine processing, example edition. Has hemostatic and blood stasis dispelling effects. The nodus Nelumbinis Rhizomatis charcoal is rhizome nodus of Nelumbo Nucifera Gaertn of Nymphaeaceae. Digging rhizome (rhizoma Nelumbinis) in autumn and winter, cutting into segments, cleaning, sun drying, and removing fibrous root. The lotus node is cylindrical, 2-4 cm long and 2 cm in diameter. The surface is grayish yellow or grayish brown, the node is expanded, has a plurality of fibrous roots or root marks, the residual surfaces at two ends have cracks, and the product is light and hard, is not easy to break, has 7 to 9 larger round holes in the cross section, has different sizes, has no smell, and is sweet and astringent. The lotus rhizome node charcoal extract is sweet and astringent, can astringe to stop bleeding and also can dissipate blood stasis, and has the characteristic of stopping bleeding without retaining blood stasis.

The ranunculus ternatus thunb is distributed in places such as Guangdong, Hunan and Guangxi in continental China, grows in areas with the altitude of 400-750 meters, usually grows in hillside shrubs or sparse forests, and is not artificially introduced and cultivated at present. The other names are ochre, rhizoma dioscoreae, chicken bloody lotus, blood mother, radix salviae miltiorrhizae, golden flower fruit, red girl, blood of girl, bovine bloody lotus and dyed potato. The ethanol extract of Ranunculus japonicus has good hemostatic and blood coagulation effects, and mainly contains tannin and glycosides. The protein in exudate after the wound is solidified to form a scabbing film, thereby reducing secretion, preventing infection, contracting the micro-vessels caused by the wound, having the function of local hemostasis, being externally applied to the wound, and having the characteristics of high speed and high efficiency. The Ranunculus japonicus extract contains alkaloids, terpenes, sterols, phenols, flavonoids and quinones in addition to the above two substances, so as to improve hemostatic efficiency.

The main functions of platelets are coagulation and hemostasis, repairing damaged blood vessels. When a human body is injured and bleeds, platelets are stimulated by an activation factor of an injured part to generate platelet aggregation to form a platelet clot, so that the primary hemostasis effect is achieved, the platelets and other blood coagulation substances in blood, such as calcium ions, thrombin and the like, aggregate on a damaged blood vessel wall to form thrombus, the damaged wound and the blood vessel are blocked, and the platelets can release adrenalin to cause vasoconstriction and promote hemostasis. The ethanol extract of Ranunculus japonicus can effectively increase the number of platelets, thereby shortening bleeding time and blood coagulation time. It is because of this mechanism that the ethanol extract of ranunculus ternatus has been fully demonstrated to have good hemostatic effect.

Flos sophorae has the functions of cooling blood and stopping bleeding, and clearing liver and purging fire, and is a commonly used hemostatic in traditional Chinese medicine. Charring is one of the commonly used processing methods for Chinese herbs. The main components of the sophora japonica charred extract are rutin and tanning, and the sophoricoside and isorhamnetin-3-O-rutinose are main components with the function of stopping bleeding, so that the bleeding time can be obviously shortened.

Bioactive peptides are specific protein fragments that have a positive impact on a body function or condition and may ultimately affect human health; it is intended to be provided by a safe, reliable and consistent oral delivery system. Gastrointestinal proteolytic enzymes help to release the peptides after digestion, and these absorbed component parts are physiologically active to humans. The bioactive peptide has excellent effects on anti-inflammation, anti-hypertension, antioxidation, anticancer, antibiosis and anti-arthritis. Marine organisms possess a variety of bioactive natural components with many physiological functions related to nutritional and pharmaceutical activities, such as antioxidant, anti-inflammatory, anticancer, antibacterial, antihypertensive, anticoagulant, anti-cardiovascular diseases, and the like. Abalone is a marine gastropod which is one of the important fisheries and food industry resources for the massive marine culture in asia, africa, australia and america. The edible part of the fresh abalone contains 24 percent of protein and 0.44 percent of fat; the dry product contains protein 40%, glycogen 33.7%, fat 0.9%, and multiple vitamins and microelements, and is a high-protein and low-fat food which is very beneficial to human body. Abalone contains abundant proteins, amino acids, and mineral elements such as calcium (Ca), iron (Fe), zinc (Zn), selenium (Se), and magnesium (Mg), which are important for regulating acid-base balance of organism and maintaining excitation of nerve and muscle. Research shows that the abalone has high protein, low fat, complete amino acid types, reasonable proportion and rich vitamin E and trace elements, and the abalone meat has rich content of physiological active substances such as EPA, DHA, taurine, superoxide dismutase and the like. Research on Penwen Bell and the like shows that Haliotis diversicolor contains all essential amino acids, the content of taurine as an active substance is almost equal to the total content of free amino acids, the content of selenium (Se) as a life fire species is very high, the content of vitamins is very rich, and the concentration of phospholipid is also high. The abalone anti-inflammatory peptide extracted from abalone has higher anti-inflammatory activity, and simultaneously has most of nutrients in abalone, and has important effects on hemostasis and anti-inflammation of wounds after operations and healing.

Radix scrophulariae is a perennial herb of Scrophulariaceae, and has the functions of cooling blood, nourishing yin, purging pathogenic fire and removing toxic substance. Radix scrophulariae mainly contains polysaccharides and alkaloids. The figwort has long medicinal history, and has the effects of influencing cardiovascular systems, expanding coronary arteries, increasing myocardial nutritional blood flow, reducing blood pressure by expanding blood vessels, resisting platelet aggregation, resisting inflammation and oxidation, inhibiting bacteria, enhancing immunity and the like.

Xanthoceras sorbifolia Bunge, also known as papaya, shinyleaf yellowhorn, cliff papaya and the like, belongs to the family of soapberry and belongs to the genus xanthoceras, and the dry stem branch of xanthoceras sorbifolia is called xanthoceras sorbifolia Bunge. The traditional Chinese medicine holds that the branches, leaves, peels, flower organs and other parts of the shinyleaf yellowhorn are important medicinal materials, and the shinyleaf yellowhorn extract has the effects of resisting inflammation, improving memory and preventing and treating cardiovascular diseases. The active ingredients of xanthoceras sorbifolia are currently mainly classified into three main categories: one is triterpenes, the mother nucleus mainly comprises oleanane pentacyclic triterpenes, including oleanolic acid and a series of saponins; one is mainly flavonoid, which refers to flavonol, flavanol and flavan, and comprises myricitrin, quercetin, dihydromyricitrin, epicatechin, etc.; the other is coumarin and sterol, including aesculin, and xanthoceranin. The xanthoceras sorbifolia can inhibit exudation and edema in the early stage of inflammation, chemotaxis and migration of leukocytes in the middle stage of inflammation, inhibit the formation of granuloma in the late stage of inflammation, and have excellent anti-inflammatory effect.

The kiwi fruit contains abundant vitamin C, A, E, potassium, magnesium, cellulose, and other less common nutrients of fruits, such as folic acid, carotene, calcium, lutein, amino acids, and natural inositol. The vitamin C can strengthen the immune system, promote wound healing and absorb iron; inositol and amino acid can supplement consumed nutrition; the perfect proportion of low sodium and high potassium can supplement the physical strength lost by the patients who undergo the operation. One of the folic acid (folic acid) vitamin B complexes, which corresponds to pteroylglutamic acid (PGA), is purified from spinach leaves by michael (h.k. mitchell, 1941) and is thus named folic acid. Has effects in promoting maturation of immature cells in bone marrow, and can cause megaloblastic anemia and leukopenia due to folic acid deficiency in human. Folic acid is a substance necessary for human body to utilize sugar and amino acids, and is a substance necessary for growth and reproduction of body cells. Folic acid functions in vivo in the form of tetrahydrofolic acid, which is involved in the synthesis and conversion of purine and pyrimidine nucleotides in vivo. Folic acid plays an important role in the production of nucleic acids (ribonucleic acid, deoxyribonucleic acid). Folic acid, which helps protein metabolism and promotes the generation and maturation of erythrocytes together with vitamin B12, is an essential substance for the production of erythrocytes. Folic acid also functions as a proliferation-promoting factor for Lactobacillus casei (Lactobacillus casei) and other microorganisms. Therefore, the kiwi fruit extract can more effectively help and promote wound healing and high-speed repair, and the linolenic acid content in the kiwi fruit seed oil reaches 67.34%.

The plukenetia volubilis linneo oil is light yellow transparent oily liquid prepared by squeezing seeds of plukenetia volubilis linneo of Euphorbiaceae. The protocaulon yulin grows in tropical rainforest in Andes mountain area of south America with altitude of 80-1700m, is eaten by local native people for thousands of years in areas such as Peru, Ecuador and the like, and is introduced to China in 2006. The Plukenetia volubilis linneo oil is rich in unsaturated fatty acid, fat-soluble vitamins, trace elements, etc., and has effects of reducing blood lipid, resisting oxidation, resisting inflammation, etc. The embelia laeta oil contains inflammatory cytokine, and has excellent anti-inflammatory effect.

Eucommia ulmoides (also known as Eucomiaulmoides Oliver), a college name, is a plant of the family Eucommiaceae. The eucommia ulmoides has few free amino acids, contains a small amount of protein, is complete protein similar to most foods, and can hydrolyze and detect 8 amino acids essential to human bodies. The 15 mineral elements contained in eucommia bark are measured, wherein the mineral elements comprise trace elements such as zinc, copper and iron, and trace elements such as calcium, phosphorus, potassium and magnesium. The content of the linolenic acid in the eucommia seed oil is up to 62.95 percent.

Schisandra chinensis (school name: Schisandra chinensis (Turcz.) Baill) is dried mature fruit of Schisandra chinensis (Schisandra chinensis, Magnoliaceae) or Schisandra chinensis (Schisandra chinensis, et Wils.). The former is called as "Bei Wu Wei Zi", the latter is called as "nan Wu Wei Zi". Picking in autumn when the fruit is ripe, sun-drying or steaming, sun-drying, and removing fruit stalks and impurities. Tang et al, in the book of Xin Xiu Ben Cao, carry that "Wu Wei Pi gan sui and He Zi is pungent and bitter in the kernel and salty in flavor", so it is named as Wu Wei Zi. The schisandra fruit is divided into two kinds of south and north. The ancient medical book called him 33614c, mysterious union 34127, mysterious union, and mysterious union, listed in the Shennong herbal meridian top grade traditional Chinese medicine for the earliest time, can nourish and strengthen the strength, has high medicinal value, and has the effect of strengthening the body. The fruit contains schizandrin (Schisandrin C23H 3206), vitamin C, resin, tannin and a small amount of saccharides. Has the effects of astringing lung, relieving cough, nourishing, arresting seminal emission, relieving diarrhea and arresting sweating. The leaves and fruits can be extracted to obtain aromatic oil, and the kernel contains fatty oil. Wherein, the linoleic acid content in the schisandra chinensis seed oil can reach 93.30 percent.

The kiwi fruit seed oil, the Chinese magnoliavine fruit seed oil, the plukenetia volubilis linneo oil and the eucommia seed oil all contain a large amount of polyenoic acid, and the polyenoic acid vegetable oil has an excellent auxiliary blood fat reducing function, an antioxidant function, an anti-aging function and an anti-inflammatory function. With regard to the anti-inflammatory function, omega-3 polyenoic acid can compete with arachidonic acid for metabolism, participate in inflammation regression and tissue repair, influence the pathway of nuclear factors, change the pathway of lipid rafts and other mechanisms to achieve the anti-inflammatory effect. Linoleic acid and methyl linoleate can reduce the level of inflammation related factors including interleukin, tumor necrosis factor and nitric oxide, and has obvious improvement effect on acute and chronic inflammation. Therefore, the compound anti-inflammatory fruit oil component combines four fruit oil components with extremely high polyenoic acid content, fully exerts the anti-inflammatory effect, can provide sufficient nutrients for healing skin by utilizing other nutrient components in the fruit oil, resists inflammation and accelerates healing and wound repair.

The cell activation agent MG-60 is a mixed solution of trehalose glucoside and hydrolyzed starch, and has the main function of cell activation; protection from cell desiccation; because the cells are damaged by ultraviolet irradiation, the damage degree is reduced by adding MG-60; MG-60 inhibits the production of TNF-a, one of inflammatory cytokines, and has good anti-inflammatory effect.

Wheat is an important agricultural product and mainly planted in the middle and north areas of China, and for a long time, the wheat is mainly used for flour production. Protein is the second largest component in wheat flour, hydrolyzed wheat protein: the major amino acids of wheat, gliadin (gl5ad55) and glutenin, are rich in cystine (cyst55e), a sulfur-containing amino acid. It has effects of keeping moisture, resisting oxidation, softening and refining skin, moistening skin, and improving skin condition. Meanwhile, hydrolyzed wheat protein provides essential amino acid for the anabolism of the organism to maintain the balance of nitrogen in the body. Particularly useful for anti-inflammatory and post-surgical protein supplementation. That is, hydrolyzed wheat protein can simultaneously supplement protein nutrition, help skin repair and resist inflammation.

Allantoin, also known as 5-ureylethanolamide, ureidoacetolactam, ureidohydantoin, uretidione, is a hydantoin derivative. At present, the annual production capacity of allantoin in the world is about 5 million tons, the market demand is mainly three fields of medicine, cosmetics and agriculture, and the traditional process for extracting natural allantoin from natural animals and plants is low in content, complex in process and high in cost, so that the allantoin cannot be applied in a large scale. In medicine, allantoin has physiological functions of promoting cell growth, accelerating wound healing, softening keratin and the like, and is a good healing agent and an anti-ulcer agent for skin wounds. In addition, allantoin can be used for alleviating and treating xerosis cutis and skin ulcer, and has good therapeutic effect on inflammation. The allantoin is an amphoteric compound, can be combined with various substances to form a double salt, has the effects of protecting from light, sterilizing, preventing corrosion, relieving pain and resisting oxidation, can keep the skin moisture, and is more moist and soft.

The natural cellulose is polysaccharide which is most widely distributed and contained in nature, and has abundant sources. Current cellulose modification technologies focus primarily on both etherification and esterification. Carboxymethylation is one of the etherification techniques. Carboxymethyl cellulose (CMC) is obtained after carboxymethylation of cellulose, and the aqueous solution of the carboxymethyl cellulose has the functions of thickening, film forming, adhesion, water retention, colloid protection and the like. The high-end substitute product of carboxymethyl cellulose (CMC) is polyanionic cellulose (PAC) and anionic cellulose ether, has higher substitution degree and substitution uniformity, shorter molecular chain and more stable molecular structure, thereby having better comprehensive performance and enhanced solubility. The method is applied to all the industries where the carboxymethyl cellulose can be applied, and can provide better stability and meet higher process requirements. 2, 6-di-tert-butyl-4-methylphenol, which is a substance that can prevent polymer materials from deteriorating due to oxidation, is an effective stabilizer for medical supplies. The combination of polyanionic cellulose (PAC) and 2, 6-di-tert-butyl-4-methylphenol can effectively provide better stability for a reaction system, improve comprehensive properties such as wear resistance and the like, and simultaneously can enhance the adhesive property of medical glue and have the water retention property.

Due to the adoption of the technical scheme, the invention has the following beneficial effects:

1. the efficient anti-inflammatory hemostatic components selected by the efficient anti-inflammatory hemostatic components comprise abalone anti-inflammatory peptide, Yunnan pine moth pupa chitin, figwort polysaccharide and shinyleaf yellowhorn extract, and a first efficient anti-inflammatory system is formed by utilizing four components with completely different anti-inflammatory principles and efficacies. The abalone anti-inflammatory peptide fully combines the anti-inflammatory activity of marine life, natural and efficient Yunnan pine moth pupa chitin capable of diminishing inflammation and promoting wound healing, figwort polysaccharide which is long in medicinal history and has the effects of resisting platelet aggregation, diminishing inflammation and resisting oxidation, and xanthoceras sorbifolia-containing polysaccharide can inhibit exudation and edema in the early stage of inflammation, chemotaxis and migration of leukocytes in the middle stage of inflammation, and inhibit formation of granuloma in the later stage of inflammation, and the xanthoceras sorbifolia extract has an excellent anti-inflammatory effect. And then combining the compound anti-inflammatory fruit oil component to form a compound anti-inflammatory fruit oil system. The effective components of the two anti-inflammatory systems supplement each other, and the rapid hemostatic effects of the high-efficiency hemostatic components for shortening the bleeding time and the blood coagulation time are mutually cooperated, so that the aim of high-efficiency anti-inflammatory hemostasis is effectively fulfilled.

2. The Sinkiang arnebia euchroma ethyl acetate extract has high-efficiency hemostatic effect, and the hemostatic effect is a process of promoting the fibrinogen to be converted into fibrin by increasing the fibrinogen content. The platelet number is increased, the anticoagulation and fibrinolysis system are influenced to play a role, and exogenous and endogenous coagulation factors are not influenced. The ethanol extract of Ranunculus japonicus can effectively increase the number of platelets, thereby shortening bleeding time and blood coagulation time. Sophora japonica saponin and isorhamnetin-3-O-rutinoside are main components with hemostatic effect, and can obviously shorten bleeding time. The lotus rhizome node charcoal extract is sweet and astringent, can astringe to stop bleeding and also can dissipate blood stasis, and has the characteristic of stopping bleeding without retaining blood stasis.

The Geranium strictipes extract has strong anti-inflammatory, hemostatic and blood coagulation effects, and the hemostatic effect of the Geranium strictipes extract with high dosage is superior to that of Yunan Yuan Zi. The invention fully combines different hemostasis special effects of five substances in the high-efficiency hemostasis component, constructs a rapid and high-efficiency hemostasis system, and is used for combining two anti-inflammatory systems to achieve the purpose of high-efficiency anti-inflammatory hemostasis.

3. The composite anti-inflammatory fruit oil selected by the medical adhesive with the efficient anti-inflammatory and hemostatic functions is a strong fruit oil anti-inflammatory system formed by four kinds of fruit oil with anti-inflammatory effects through the synergistic use of the kiwi fruit seed oil, the Chinese magnoliavine fruit oil, the plukenetia volubilis linneo oil and the eucommia seed oil. The kiwi fruit seed oil, the Chinese magnoliavine fruit seed oil, the plukenetia volubilis linneo oil and the eucommia seed oil all contain a large amount of polyenoic acid, and the polyenoic acid vegetable oil has an excellent auxiliary blood fat reducing function, an antioxidant function, an anti-aging function and an anti-inflammatory function. With regard to the anti-inflammatory function, omega-3 polyenoic acid can compete with arachidonic acid for metabolism, participate in inflammation regression and tissue repair, influence the pathway of nuclear factors, change the pathway of lipid rafts and other mechanisms to achieve the anti-inflammatory effect. Linoleic acid and methyl linoleate can reduce the level of inflammation related factors including interleukin, tumor necrosis factor and nitric oxide, and has obvious improvement effect on acute and chronic inflammation. Therefore, the compound anti-inflammatory fruit oil component combines four fruit oil components with extremely high polyenoic acid content, fully exerts the anti-inflammatory effect, can provide sufficient nutrients for healing skin by utilizing other nutrient components in the fruit oil, resists inflammation and accelerates healing and wound repair.

4. The medical glue with high-efficiency anti-inflammatory and hemostatic functions is particularly added with allantoin, and has unique and important effects. Allantoin has the physiological functions of promoting cell growth, accelerating wound healing, softening keratin and the like, and is a good healing agent for skin wounds. In addition, allantoin can be used for alleviating and treating xerosis cutis and skin ulcer, and has good therapeutic effect on inflammation. The allantoin is an amphoteric compound, can be combined with various substances to form a double salt, has the effects of protecting from light, sterilizing, preventing corrosion, relieving pain and resisting oxidation, can keep the skin moisture, and is more moist and soft. The allantoin is used and simultaneously acts as a formaldehyde inhibitor in the system, and effectively acts as the formaldehyde inhibitor, so that the system does not need to additionally add a separate formaldehyde inhibitor and a preservative.

5. Each additive component except the stabilizer selected by the medical glue with the efficient anti-inflammatory and hemostatic functions has certain anti-inflammatory and hemostatic functions, including cell activator MG-60, wheat hydrolyzed protein, allantoin and the like which are indispensable components of the whole efficient anti-inflammatory and hemostatic product, and the effects of various efficient anti-inflammatory and hemostatic components are natural, so that the medical glue with the efficient anti-inflammatory and hemostatic functions is prepared.

The medical adhesive with the efficient anti-inflammatory and hemostatic functions has the bonding strength of more than 60N, the hemostatic time for wounds is less than 110 seconds, the overall cure rate is high, the biocompatibility is high, no stimulation is caused to wound tissues, the sensitization rate is reduced, the comprehensive performance is excellent, the application requirement of clinical application on medical adhesives is met, and the pain of patients needing to be born is reduced to the maximum extent by improving the efficient anti-inflammatory and hemostatic performance of the medical adhesives.

Detailed Description

The invention is described in detail below by means of specific examples:

example 1

A medical adhesive with high-efficiency anti-inflammatory and hemostatic functions comprises the following components in parts by weight: 20 parts of n-octyl a-cyanoacrylate, 25 parts of isooctyl a-cyanoacrylate, 2 parts of polyvinyl acetate, 12 parts of efficient anti-inflammatory component, 13 parts of efficient hemostatic component, MG-603 parts of cell activator, 8 parts of allantoin, 1 part of hydrolyzed wheat protein, 1 part of stabilizer, 150 parts of composite anti-inflammatory fruit oil component and 200 parts of sterile water; the high-efficiency anti-inflammatory component comprises 2 parts of abalone anti-inflammatory peptide, 3 parts of Yunnan pine moth pupa chitin, 6 parts of figwort polysaccharide and 5 parts of shinyleaf yellowhorn extract by weight; the efficient hemostatic components comprise 5 parts of garden burnet root extract, 3 parts of Sinkiang arnebia root extract, 3 parts of buttercup extract, 6 parts of lotus rhizome node carbon extract and 6 parts of sophora flower carbon extract by weight; the composite anti-inflammatory fruit oil component comprises, by weight, 4 parts of kiwi fruit seed oil, 3 parts of plukenetia volubilis linneo oil, 2 parts of eucommia seed oil and 5 parts of schisandra fruit oil. The stabilizer is prepared from polyanionic cellulose and 2, 6-di-tert-butyl-4-methylphenol according to the weight portion of 10: 1 are combined. The Geranium strictipes extract in the high-efficiency hemostatic component is Geranium strictipes ethyl acetate extract; the arnebia euchroma (Royle) Johnst extract is an ethyl acetate extract of arnebia euchroma (Royle) Johnst; the lotus rhizome node charcoal extract is an ethyl acetate extract of the lotus rhizome node charcoal; the sophora japonica charred extract is an ethyl acetate extract of sophora japonica charred, and the ranunculus ternatus extract is an ethanol extract of ranunculus ternatus.

The medical adhesive prepared by the embodiment is used for smearing wounds, and relevant performance tests are carried out, wherein the test results are as follows: the medical adhesive with the efficient anti-inflammatory and hemostatic functions has the bonding strength of 61N, the hemostatic time on wounds of 109 seconds and high overall cure rate.

Example 2

A medical adhesive with high-efficiency anti-inflammatory and hemostatic functions comprises the following components in parts by weight: 22 parts of n-octyl a-cyanoacrylate, 28 parts of isooctyl a-cyanoacrylate, 4 parts of polyvinyl acetate, 16 parts of efficient anti-inflammatory component, 18 parts of efficient hemostatic component, MG-604 parts of cell activator, 9 parts of allantoin, 1 part of hydrolyzed wheat protein, 1 part of stabilizer, 180 parts of composite anti-inflammatory fruit oil component and 200 parts of sterile water; the high-efficiency anti-inflammatory component comprises 2 parts of abalone anti-inflammatory peptide, 3 parts of Yunnan pine moth pupa chitin, 6 parts of figwort polysaccharide and 5 parts of shinyleaf yellowhorn extract by weight; the efficient hemostatic components comprise 5 parts of garden burnet root extract, 3 parts of Sinkiang arnebia root extract, 3 parts of buttercup extract, 6 parts of lotus rhizome node carbon extract and 6 parts of sophora flower carbon extract by weight; the composite anti-inflammatory fruit oil component comprises, by weight, 4 parts of kiwi fruit seed oil, 3 parts of plukenetia volubilis linneo oil, 2 parts of eucommia seed oil and 5 parts of schisandra fruit oil. The stabilizer is prepared from polyanionic cellulose and 2, 6-di-tert-butyl-4-methylphenol according to the weight portion of 10: 1 are combined. The Geranium strictipes extract in the high-efficiency hemostatic component is Geranium strictipes ethyl acetate extract; the arnebia euchroma (Royle) Johnst extract is an ethyl acetate extract of arnebia euchroma (Royle) Johnst; the lotus rhizome node charcoal extract is an ethyl acetate extract of the lotus rhizome node charcoal; the sophora japonica charred extract is an ethyl acetate extract of sophora japonica charred, and the ranunculus ternatus extract is an ethanol extract of ranunculus ternatus.

The medical adhesive prepared by the embodiment is used for smearing wounds, and relevant performance tests are carried out, wherein the test results are as follows: the medical adhesive with the efficient anti-inflammatory and hemostatic functions has the bonding strength of 62N, the hemostatic time on wounds of 106 seconds and high overall cure rate.

Example 3

A medical adhesive with high-efficiency anti-inflammatory and hemostatic functions comprises the following components in parts by weight: 24 parts of n-octyl a-cyanoacrylate, 32 parts of isooctyl a-cyanoacrylate, 5 parts of polyvinyl acetate, 18 parts of efficient anti-inflammatory component, 20 parts of efficient hemostatic component, MG-605 parts of cell activator, 10 parts of allantoin, 1 part of hydrolyzed wheat protein, 1 part of stabilizer, 200 parts of composite anti-inflammatory fruit oil component and 200 parts of sterile water; the high-efficiency anti-inflammatory component comprises 2 parts of abalone anti-inflammatory peptide, 3 parts of Yunnan pine moth pupa chitin, 6 parts of figwort polysaccharide and 5 parts of shinyleaf yellowhorn extract by weight; the efficient hemostatic components comprise 5 parts of garden burnet root extract, 3 parts of Sinkiang arnebia root extract, 3 parts of buttercup extract, 6 parts of lotus rhizome node carbon extract and 6 parts of sophora flower carbon extract by weight; the composite anti-inflammatory fruit oil component comprises, by weight, 4 parts of kiwi fruit seed oil, 3 parts of plukenetia volubilis linneo oil, 2 parts of eucommia seed oil and 5 parts of schisandra fruit oil. The stabilizer is prepared from polyanionic cellulose and 2, 6-di-tert-butyl-4-methylphenol according to the weight portion of 10: 1 are combined. The Geranium strictipes extract in the high-efficiency hemostatic component is Geranium strictipes ethyl acetate extract; the arnebia euchroma (Royle) Johnst extract is an ethyl acetate extract of arnebia euchroma (Royle) Johnst; the lotus rhizome node charcoal extract is an ethyl acetate extract of the lotus rhizome node charcoal; the sophora japonica charred extract is an ethyl acetate extract of sophora japonica charred, and the ranunculus ternatus extract is an ethanol extract of ranunculus ternatus.

The medical adhesive prepared by the embodiment is used for smearing wounds, and relevant performance tests are carried out, wherein the test results are as follows: the medical adhesive with the efficient anti-inflammatory and hemostatic functions has the bonding strength of 61.5N, the hemostatic time on wounds of 107 seconds and high overall cure rate.

Example 4

A medical adhesive with high-efficiency anti-inflammatory and hemostatic functions comprises the following components in parts by weight: 25 parts of n-octyl a-cyanoacrylate, 35 parts of isooctyl a-cyanoacrylate, 6 parts of polyvinyl acetate, 20 parts of efficient anti-inflammatory component, 23 parts of efficient hemostatic component, 606 parts of cell activator MG-606 parts, 10 parts of allantoin, 1 part of hydrolyzed wheat protein, 1 part of stabilizer, 220 parts of composite anti-inflammatory fruit oil component and 200 parts of sterile water; the high-efficiency anti-inflammatory component comprises 2 parts of abalone anti-inflammatory peptide, 3 parts of Yunnan pine moth pupa chitin, 6 parts of figwort polysaccharide and 5 parts of shinyleaf yellowhorn extract by weight; the efficient hemostatic components comprise 5 parts of garden burnet root extract, 3 parts of Sinkiang arnebia root extract, 3 parts of buttercup extract, 6 parts of lotus rhizome node carbon extract and 6 parts of sophora flower carbon extract by weight; the composite anti-inflammatory fruit oil component comprises, by weight, 4 parts of kiwi fruit seed oil, 3 parts of plukenetia volubilis linneo oil, 2 parts of eucommia seed oil and 5 parts of schisandra fruit oil. The stabilizer is prepared from polyanionic cellulose and 2, 6-di-tert-butyl-4-methylphenol according to the weight portion of 10: 1 are combined. The Geranium strictipes extract in the high-efficiency hemostatic component is Geranium strictipes ethyl acetate extract; the arnebia euchroma (Royle) Johnst extract is an ethyl acetate extract of arnebia euchroma (Royle) Johnst; the lotus rhizome node charcoal extract is an ethyl acetate extract of the lotus rhizome node charcoal; the sophora japonica charred extract is an ethyl acetate extract of sophora japonica charred, and the ranunculus ternatus extract is an ethanol extract of ranunculus ternatus.

The medical adhesive prepared by the embodiment is used for smearing wounds, and relevant performance tests are carried out, wherein the test results are as follows: the medical adhesive with the efficient anti-inflammatory and hemostatic functions has the bonding strength of 62N, the hemostatic time on wounds of 105 seconds and high overall cure rate.

In the above embodiments

The preparation method of the Sinkiang arnebia root extract comprises the following steps:

drying and powdering arnebia euchroma, sieving with a 100-mesh sieve to obtain arnebia euchroma powder, adding 95% ethanol solution, and ultrasonically extracting at 45 deg.C and 200W for 35min to obtain extractive solution; filtering the extractive solution, and concentrating under reduced pressure to obtain slurry; the slurry was mixed at a ratio of 1: dissolving the extract in deionized water at a volume ratio of 15, stirring, shaking uniformly, and sterilizing by a microporous membrane filter to obtain the arnebia euchroma (Royle) Johnst extract.

The preparation method of the ranunculus japonicus extract comprises the following steps:

the Ranunculus japonicus extract is prepared by extracting Ranunculus japonicus with 80% ethanol water solution as solvent at a ratio of 2:1 in 70 deg.C hot water for 3 hr, standing in dark place for 15 hr, filtering, rotary evaporating for concentration to 1.5g/ml, sterilizing the concentrated solution with microporous membrane, and air drying at 500 deg.C.

The preparation method of the shinyleaf yellowhorn extract comprises the following steps:

washing off silt on the surface of the shinyleaf yellowhorn by using flowing water, introducing an ozone generator into sterile water to wash the shinyleaf yellowhorn again, crushing pulp into pulp, adding deionized water according to the volume of 30% of the pulp, adding 2.5% of pectinase at the same time, stirring uniformly, and standing for 50 min at 33 ℃; adding the supernatant into 90% ethanol solution, ultrasonic extracting at 35 deg.C and 100W ultrasonic power for 20min, and centrifuging at 4000rpm/min for 10 min; after concentrating the supernatant from the centrifugation to a semi-fluid slurry, the slurry was mixed at a ratio of 1: dissolving 12 volume ratio in deionized water, stirring, shaking, and sterilizing with microporous membrane to obtain xanthoceras sorbifolia extract.

The extraction method of the Yunnan pine moth pupa chitin comprises the following specific operations:

The preparation method of the medical glue with the efficient anti-inflammatory and hemostatic functions comprises the following steps:

Performance testing

The medical adhesive prepared by the embodiment is used for smearing the wound, the bonding strength of the medical adhesive with the efficient anti-inflammatory and hemostatic functions is more than 60N, the hemostatic time for the wound is less than 110 seconds, the overall cure rate is high, the biocompatibility is high, no stimulation is caused to wound tissues, the sensitization rate is reduced, the comprehensive performance is excellent, and the medical adhesive meets the clinical application requirements for the medical adhesive.

The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications of equivalent structures and equivalent processes, which are made by the present specification, or directly or indirectly applied to other related technical fields, are included in the scope of the present invention.

Claims

1. The preparation method of the medical adhesive with the efficient anti-inflammatory and hemostatic functions comprises the following components in parts by weight: 20-25 parts of a-n-octyl cyanoacrylate, 25-35 parts of a-isooctyl cyanoacrylate, 2-6 parts of polyvinyl acetate, 12-20 parts of efficient anti-inflammatory component, 13-23 parts of efficient hemostatic component, MG-603-6 parts of cell activator, 8-10 parts of allantoin, 1 part of hydrolyzed wheat protein, 1 part of stabilizer, 150 parts of composite anti-inflammatory fruit oil component, 220 parts of sterile water and 200 parts of sterile water;

the stabilizer is prepared from polyanionic cellulose and 2, 6-di-tert-butyl-4-methylphenol according to the weight part of 10: 1, combining the components;

the Geranium strictipes extract in the high-efficiency hemostasis component is Geranium strictipes ethyl acetate extract; the Sinkiang arnebia root extract is an ethyl acetate extract of Sinkiang arnebia root; the lotus rhizome node charcoal extract is an ethyl acetate extract of lotus rhizome node charcoal; the sophora japonica charred extract is an ethyl acetate extract of sophora japonica charred, and the ranunculus ternatus extract is an ethanol extract of ranunculus ternatus;

the composite anti-inflammatory fruit oil component comprises, by weight, 4 parts of kiwi fruit seed oil, 3 parts of mei teng fruit oil, 2 parts of eucommia seed oil and 5 parts of schisandra fruit oil;

the preparation method comprises the following steps: