Biological liquid medicine for promoting cartilage tissue regeneration for knee joint injection

Abstract

The invention provides a biological liquid medicine for promoting cartilage tissue regeneration by being injected into knee joints. The biological liquid medicine comprises the following components: 3%-4% of modified xanthan gum, 1.5%-2.5% of chitosan lactate wrapped by lipidosome, 0.2%-0.6% of strontium bromide, 1%-2% of disodium hydrogen phosphate, 1%-2% of sodium dihydrogen phosphate and the balance of water for injection to 100%, the modified xanthan gum is carboxymethylated xanthan gum. According to the biological liquid medicine, modified xanthan gum, chitosan lactate wrapped by lipidosome and strontium bromide are added, long-acting retention of the modified xanthan gum provides a stable release environment for the lipidosome and the strontium bromide, the lipidosome accurately delivers the chitosan lactate to an injured part, and the lipidosome and the strontium bromide act on ions to strengthen cartilage cell proliferation and matrix secretion, so that the cartilage cell proliferation and matrix secretion are enhanced; the three components are combined to improve the cartilage tissue damage repair degree of the knee joint and improve the cartilage tissue regeneration effect.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biomedical materials, and particularly relates to a biological liquid for promoting cartilage tissue regeneration for injection of knee joints. BACKGROUND

[0002] Osteoarthritis (OA) is the most common chronic joint disease in the world, and its core pathological features are progressive degradation of cartilage, remodeling of subchondral bone, and inflammatory response of joints. The cartilage repair material for injection is a kind of biomedical material for improving joint lubrication and promoting repair of cartilage damage by intra-articular injection, which is mainly used for clinical treatment of knee cartilage injury, osteoarthritis and other degenerative diseases. Its core function is to deliver active ingredients locally to relieve pain and induce cartilage tissue regeneration, which is the mainstream choice for non-surgical treatment of cartilage injury at present.

[0003] In the treatment of knee cartilage injury, the existing repair material for injection mainly faces four key challenges: the drug solution is easily lost with joint fluid metabolism, resulting in short action time; the drug diffuses to the surrounding tissue, causing insufficient local effective concentration; the function is limited to physical lubrication or single proliferation promotion, and cannot simultaneously repair cartilage matrix and subchondral bone; and local inflammatory response caused by high concentration of components or unbalanced osmotic pressure.

[0004] In view of the above problems, the existing technology has tried various improvement ideas, such as prolonging the retention time by improving the viscoelasticity of the material (such as sodium hyaluronate), strengthening the repair by loading the proliferation-promoting components (such as chitosan gel), and adjusting the cell function by adding ion components (such as bromide ions promoting differentiation). Among them, sodium hyaluronate, as the most widely used representative material in clinical application, although it forms a lubricating film in the joint cavity through high viscoelasticity, to a certain extent, prolongs the retention time, but its actual application still has significant limitations: due to the short retention time, frequent injection is required to maintain the efficacy, which is difficult to continuously stimulate cartilage regeneration; only physical lubrication is provided, which cannot actively promote cartilage cell proliferation or matrix secretion, and cannot act on the subchondral bone to promote mineralization, resulting in incomplete repair of the injury; in addition, when the concentration is increased to prolong the retention time, it is easy to cause unbalanced osmotic pressure or local inflammation, which destroys the stable microenvironment required for cartilage regeneration, and hinders the repair process. The functional limitations and application defects of such materials make it an urgent need for clinical injection of biological liquids with long-acting retention, targeted delivery of active ingredients, multi-effect repair and good biocompatibility.

[0005] Therefore, there is an urgent need for a biological liquid for promoting cartilage tissue regeneration for injection of knee joints, which can achieve long-acting joint cavity retention, precise targeted delivery of active ingredients, and good biocompatibility. SUMMARY

[0006] The application aims to provide a biological liquid for promoting cartilage tissue regeneration for injection of knee joints, which is suitable for repair treatment of diseases such as joint cartilage injury and osteoarthritis, and has long-acting retention, targeted delivery and high-efficiency repair function for cartilage injury.

[0007] To achieve the above-mentioned purpose, the application provides the following technical scheme: a biological liquid for promoting cartilage tissue regeneration for injection of knee joints, comprising the following components in percentage by mass: modified xanthan gum 3%-4%, liposome-coated chitosan lactate 1.5%-2.5%, strontium bromide 0.2%-0.6%, disodium hydrogen phosphate 1%-2%, sodium dihydrogen phosphate 1%-2%, and injection water to 100%.

[0008] Preferably, the biological liquid comprises the following components in percentage by mass: modified xanthan gum 3.5%, liposome-coated chitosan lactate 2%, strontium bromide 0.5%, disodium hydrogen phosphate 1.5%, sodium dihydrogen phosphate 1.5%, and injection water to 100%.

[0009] Preferably, the average relative molecular mass of the modified xanthan gum is 1200 million, and the carboxymethyl substitution degree is 0.5.

[0010] Further, the concentration of lactic acid in the liposome-coated chitosan lactate is 50 mmol / L-100 mmol / L, the liposome is composed of DSPC (distearoyl phosphatidylcholine) and cholesterol at a mass ratio of 2:1-4:1, and the particle size is 100 nm-200 nm; the strontium bromide provides a bromide ion concentration of 1 mM-3 mM and a strontium ion concentration of 0.5 mM-2 mM.

[0011] Preferably, the concentration of lactic acid in the liposome-coated chitosan lactate is 80 mmol / L, the liposome is composed of DSPC and cholesterol at a mass ratio of 3:1; and the strontium bromide provides a bromide ion concentration of 2 mM and a strontium ion concentration of 1 mM.

[0012] Further, the pH value of the biological liquid is 7.2-7.4, and the osmotic pressure is 280 mOsmol / L-320 mOsmol / L.

[0013] Preferably, the pH value of the biological liquid is 7.3, and the osmotic pressure is 300 mOsmol / L.

[0014] Further, the preparation method of the modified xanthan gum is as follows: xanthan gum is added into a NaOH solution, chloroacetic acid is slowly added after stirring, the pH value is adjusted to 7 after continuous reaction, and the modified xanthan gum is obtained through ethanol precipitation and drying.

[0015] Further, the preparation method of the liposome-encapsulated chitosan lactate is as follows: chitosan is added into a lactic acid solution and stirred until completely dissolved to obtain a chitosan lactate solution; lecithin and cholesterol are dissolved in chloroform and rotary evaporated into a lipid film; the chitosan lactate solution is added and ultrasonically broken after water bath, filtered through a filter membrane, and freeze-dried to obtain the liposome-encapsulated chitosan lactate.

[0016] Further, the solid-liquid ratio of the chitosan and lactic acid solution is 1:40-50.

[0017] Compared with the prior art, the advantages and beneficial effects of the present application are as follows: 1. The present application is an injection type biological liquid, which uses modified xanthan gum with a molecular weight of 10-15 million as one of the raw materials, which can maintain low shear flow during injection to facilitate needle tube injection, and after injection, it forms a highly viscoelastic gel due to the ultra-high molecular weight characteristics, and significantly reduces the diffusion of the liquid by the hydrogen bond between the carboxymethyl-modified carboxyl and the cartilage matrix chondroitin sulfate, providing a long-acting environment for cartilage tissue regeneration; 2. The biological liquid of the present application uses liposome-encapsulated chitosan lactate as one of the raw materials, which promotes cartilage cell proliferation, significantly improves the cartilage cell proliferation rate, and induces cell to secrete glycosaminoglycan (GAG), effectively improves the content of GAG, and accelerates the regeneration and repair of damaged cartilage matrix; 3. The biological liquid of the present application uses strontium bromide as one of the raw materials, which can promote the differentiation of cartilage cells to mature phenotype and directly participate in cartilage tissue regeneration; strontium ions can promote the differentiation of osteoblasts and the mineralization of bone matrix. Both of them work together to realize the synchronous promotion of cartilage surface regeneration and subchondral bone mineralization, and strengthen the overall regeneration and repair ability of the injection type liquid; 4. The biological liquid of the present application uses modified xanthan gum, liposome-encapsulated chitosan lactate and strontium bromide, which can provide a stable release environment for the liposome and strontium bromide under the synergistic action of the three, avoid rapid drug loss, and improve the effect of the drug; the liposome can accurately deliver chitosan lactate to the damaged site, and the ion action of strontium bromide can synergize under local high concentration to strengthen cartilage cell proliferation and matrix secretion; the lubricating protection of xanthan gum and the anti-inflammatory effect of strontium bromide can also reduce the interference of the microenvironment. The combination of the three can effectively improve the degree of cartilage tissue damage repair of the knee joint and greatly improve the effect of cartilage tissue regeneration; 5. The pH (7.2-7.4) and osmotic pressure (280-320 mOsmol / L) of the biological liquid of the present application are highly matched with the physiological environment of the joint fluid, which can avoid the phenomenon of local irritation after injection; at the same time, it can provide a low-inflammatory and stable microenvironment for cartilage tissue regeneration, further improving the medicinal efficacy of the liquid. DETAILED DESCRIPTION

[0018] The technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of the present application.

[0019] Embodiment 1 The present embodiment provides a biological liquid medicine for promoting cartilage tissue regeneration for injection of knee joint, which comprises modified xanthan gum 3.5%, liposome-encapsulated chitosan lactate 2.0%, disodium hydrogen phosphate 1.5%, sodium dihydrogen phosphate 1.5%, strontium bromide 0.5%, and water for injection 91.0% by mass percentage.

[0020] The average relative molecular mass of the modified xanthan gum is 12 million, and the carboxymethyl substitution degree is 0.5; the concentration of lactic acid in the liposome-encapsulated chitosan lactate is 80 mmol / L, the liposome is composed of DSPC and cholesterol at a mass ratio of 3:1, and the particle size is 100-150 nm; the strontium bromide provides a bromide ion concentration of 2 mM and a strontium ion concentration of 1 mM.

[0021] The preparation method of the biological liquid medicine comprises the following steps: (1) Preparation of modified xanthan gum: add xanthan gum to 0.5 mol / L NaOH solution (solid-liquid ratio 1:20), stir at 50°C for 2 h, slowly add chloroacetic acid (1.5 times the mass of xanthan gum), continue to react for 4 h, adjust the pH to 7, precipitate with ethanol, and dry to obtain carboxymethylated xanthan gum; (2) Preparation of liposome-encapsulated chitosan lactate: first, add chitosan to 0.5% lactic acid solution (solid-liquid ratio 1:50) and stir until completely dissolved to obtain a chitosan lactate solution; then dissolve lecithin (100 mg) and cholesterol (20 mg) in chloroform and rotary evaporate to form a lipid film; add the chitosan lactate solution, water bath at 37°C for 1 h, ultrasonic crushing (200 W, 5 min), pass through a 0.22 μm filter membrane, and freeze-dry to obtain liposome-encapsulated chitosan lactate with a particle size of 100-150 nm; (3) Preparation of the liquid medicine: add the modified xanthan gum to water for injection (40°C), add disodium hydrogen phosphate and sodium dihydrogen phosphate, and stir until completely dissolved (200 rpm, 30 min); add strontium bromide and stir for 10 min until dissolved; finally, add the liposome-encapsulated chitosan, stir at low speed (100 rpm, 15 min), filter sterilization through a 0.22 μm filter membrane, and the biological liquid medicine is obtained.

[0022] Embodiment 2 The embodiment provides a biological liquid medicine for promoting cartilage tissue regeneration for injection of knee joints, which comprises modified xanthan gum 3%, liposome-encapsulated chitosan lactate 1.5%, strontium bromide 0.2%, sodium phosphate dibasic 1%, sodium phosphate monobasic 1% and water for injection 93.3% in percentage by mass. Other components are the same as those in the embodiment 1.

[0023] Embodiment 3 The embodiment provides a biological liquid medicine for promoting cartilage tissue regeneration for injection of knee joints, which comprises modified xanthan gum 4%, liposome-encapsulated chitosan lactate 2.5%, strontium bromide 0.6%, sodium phosphate dibasic 2%, sodium phosphate monobasic 2% and water for injection 88.9% in percentage by mass. Other components are the same as those in the embodiment 1.

[0024] Comparative example 1 The comparative example is different from the embodiment 1 in that xanthan gum is used instead of the modified xanthan gum in the embodiment 1. The specific components include xanthan gum 3.5%, liposome-encapsulated chitosan lactate 2.0%, sodium phosphate dibasic 1.5%, sodium phosphate monobasic 1.5%, strontium bromide 0.5% and water for injection 91.0%.

[0025] Comparative example 2 The comparative example is different from the embodiment 1 in that the liposome-encapsulated chitosan lactate in the embodiment 1 is replaced by chitosan lactate without liposome encapsulation. The specific components include modified xanthan gum 3.5%, chitosan lactate 2.0%, sodium phosphate dibasic 1.5%, sodium phosphate monobasic 1.5%, strontium bromide 0.5% and water for injection 91.0%.

[0026] Comparative example 3 The comparative example is different from the embodiment 1 in that strontium bromide is not added. The specific components include modified xanthan gum 3.5%, liposome-encapsulated chitosan lactate 2.0%, sodium phosphate dibasic 1.5%, sodium phosphate monobasic 1.5% and water for injection 91.0%.

[0027] The performance (cartilage cell proliferation rate, GAG secretion amount and pathological integral) of the biological liquid medicine prepared in the embodiment 1-3 and the comparative examples 1-3 is tested, and the testing method is as follows: Cartilage cell proliferation rate: rabbit knee joint cartilage cells (P2 generation) are taken, and 1×10 4CCK-8 method: 2×103 cells / well were inoculated in 96-well plates, and DMEM high-sugar culture medium containing 10% biological liquid was added. After 72 hours of culture, the absorbance (OD450nm) was detected by CCK-8 method. The steps of CCK-8 method for detecting absorbance were as follows: cell suspension was inoculated into a 96-well plate and pre-cultured to the logarithmic growth phase 7; 10ml CCK-8 reagent was added to each well to avoid bubble generation, and the plate was incubated in a 37°C incubator for 1-4 hours. The absorbance (OD value) was measured at 450nm wavelength by using an enzyme-labeled instrument. The cartilage cell proliferation rate = (experimental group OD-blank group OD) / blank group OD x 100%.

[0028] GAG secretion: rabbit knee joint cartilage cells (P2 generation) were taken, 2×10 5 CCK-8 method: 2×103 cells / well were inoculated in 96-well plates, and DMEM high-sugar culture medium containing 10% biological liquid was added. After 72 hours of culture, the absorbance (OD450nm) was detected by CCK-8 method. The steps of CCK-8 method for detecting absorbance were as follows: cell suspension was inoculated into a 96-well plate and pre-cultured to the logarithmic growth phase 7; 10ml CCK-8 reagent was added to each well to avoid bubble generation, and the plate was incubated in a 37°C incubator for 1-4 hours. The absorbance (OD value) was measured at 450nm wavelength by using an enzyme-labeled instrument. The cartilage cell proliferation rate = (experimental group OD-blank group OD) / blank group OD x 100%.

[0029] Pathological score of osteoarthritis (OA): The internationally recognized OARSI (Osteoarthritis Research Society International) histological scoring system was used to evaluate the drug repair effect by quantifying the degree of cartilage damage. The specific operation process and scoring criteria are as follows: (1) Establishment of experimental animal model Animal selection: 6-month-old New Zealand white rabbits (male and female, body weight 2.5-3.0 kg), adaptive feeding for 1 week (environment: temperature 22±2°C, humidity 50±5%, 12h day-night rhythm).

[0030] Modeling method: Anesthesia: 3% sodium pentobarbital (1mL / kg body weight) was injected through the ear vein, and the animal was fixed on the operating table. The skin and joint capsule of the right knee joint were incised along the medial patellar ligament, and the joint cavity was exposed. A 1mL syringe was used to slowly inject 0.3mL papain solution (concentration: 3mg / mL, solvent: 0.1mol / L cysteine hydrochloride buffer, pH6.0) into the joint cavity.

[0031] Arthrocentesis: The right knee joint was taken, the skin and joint capsule were incised along the medial patellar ligament, and the joint cavity was exposed. A 1mL syringe was used to slowly inject 0.3mL papain solution (concentration: 3mg / mL, solvent: 0.1mol / L cysteine hydrochloride buffer, pH6.0) into the joint cavity.

[0032] Postoperative treatment: The joint capsule and skin were sutured, and penicillin (80,000 U / kg) was injected intramuscularly to prevent infection. The animals were fed freely, and the modeling was repeated once on the 7th day after modeling to ensure the stability of the cartilage injury model.

[0033] (2) Group intervention and sampling Grouping design: After successful modeling (2 weeks after modeling, confirmed by MRI that the cartilage was damaged), the experimental rabbits were randomly divided into 7 groups (blank group, examples 1-3, and comparative examples 1-3), 6 in each group (12 knees).

[0034] Intervention method: Inject 0.5 mL of corresponding drug solution into each joint cavity (inject the same volume of normal saline into the blank group), inject once a week, and continuously intervene for 4 weeks.

[0035] Sampling time: 48 h after the last injection (to ensure that the drug has fully taken effect), the animals were euthanized by ear vein injection of excessive sodium pentobarbital (5 mL / kg), and the knee joint (including femoral condyle, tibial plateau, and meniscus) was completely cut.

[0036] (3) Histological sample preparation Fixation: Immediately after sampling, the knee joint was fixed in 10% neutral formalin solution for 48 h (4°C, dark).

[0037] Decalcification: Transfer to EDTA decalcification solution (10% disodium ethylenediaminetetraacetate, pH 7.4), replace the decalcification solution every 3 days, until complete decalcification is confirmed by X-ray detection (about 14-21 days).

[0038] Dehydration and embedding: Dehydrate in 70%→80%→90%→95%→100% ethanol gradient (2 h per gradient), xylene transparency (2 x 1 h), and paraffin embedding (58°C constant temperature).

[0039] Sectioning and staining: Cut 5 μm thick continuous sections along the sagittal plane (3 representative sections for each of the femoral condyle and tibial plateau), and perform routine HE staining (hematoxylin-eosin) and toluidine blue staining (to show glycosaminoglycan GAG distribution) [3].

[0040] (4) OARSI scoring criteria (0-6 points, the higher the score, the more severe the damage) The scoring was completed independently by 2 OARSI-trained pathologists, 6 sections were taken from each animal (3 from the femoral condyle and 3 from the tibial plateau), 5 high-power fields (400 x) were selected from each section, the average value was calculated, and 0-3 points were mild damage and 4-6 points were moderate to severe damage.

[0041] The performance test results are shown in Table 1: Table 1 Performance test results

[0042] From the performance test results, the chondrocyte proliferation rate of Examples 1-3 is ≥ 139.8% (≥ 39.8% higher than the blank group), the GAG secretion amount is ≥ 38.7 μg / mL (≥ 215% higher than the blank group), and the pathological score is ≤ 1.8 (≥ 65% lower than the blank group), indicating that the biological liquid provided by the application can significantly promote chondrocyte proliferation, increase GAG secretion, and reduce joint pathological damage, especially the comprehensive performance of Example 1 is the most outstanding (proliferation rate 148.2%, GAG 45.6 μg / mL, pathological score 1.1). This is mainly because: the modified xanthan gum (carboxymethylation) increases the molecular hydrophilicity and viscoelasticity, prolongs the retention time of the liquid in the joint cavity, and ensures the continuous effect of the active ingredients; the liposome-encapsulated chitosan lactate improves the local effective concentration by targeted delivery (specific binding of the surface charge of the liposome to the negative charge of the chondrocytes), promotes chondrocyte proliferation and matrix secretion; strontium bromide directly induces chondrocytes to synthesize GAG and other matrix components, and the three work together to achieve cartilage regeneration and repair.

[0043] Compared with Example 1, Comparative Example 1 does not use modified reduced gum as raw material, and replaces the modified xanthan gum of Example 1 with reduced gum. It is found that the chondrocyte proliferation rate of the biological liquid prepared by Comparative Example 1 is only 125.3% (15.5% lower than Example 1), the GAG secretion amount is 22.1 μg / mL (51.5% lower than Example 1), and the pathological score is 3.2 (190.9% higher than Example 1). This is because the unmodified xanthan gum has insufficient viscoelasticity, and the liquid is easily lost with joint fluid metabolism, resulting in insufficient delivery of active ingredients, significantly reduced chondrocyte proliferation and matrix secretion efficiency, and weakened repair effect; Compared with Example 1, Comparative Example 2 uses un-liposome-encapsulated chitosan lactate as raw material, and replaces the liposome-encapsulated chitosan lactate of Example 1 with un-liposome-encapsulated chitosan lactate. It is found that the proliferation rate of the biological liquid prepared by Comparative Example 2 is 120.7% (18.6% lower than Example 1), the GAG secretion amount is 28.5 μg / mL (37.5% lower than Example 1), and the pathological score is 2.8 (154.5% higher than Example 1). This is because the un-encapsulated chitosan lactate easily diffuses to the surrounding tissue, reducing the local effective concentration and failing to precisely act on chondrocytes, resulting in reduced matrix secretion and weakened repair effect; Compared with Example 1, Comparative Example 3 does not add strontium bromide, and the results show that, The GAG secretion amount of the biological liquid prepared by Comparative Example 3 is 25.4 μg / mL (44.3% lower than Example 1), and the pathological score is 2.5 (127.3% higher than Example 1). This is because strontium bromide is a key component for inducing chondrocytes to synthesize GAG, and the absence of strontium bromide significantly reduces the matrix secretion capacity and weakens the repair effect.

[0044] From the above analysis, it can be seen that the modified xanthan gum, liposome- wrapped chitosan lactate and strontium bromide have irreplaceable synergistic effects in prolonging the retention time, targeted delivery of active ingredients, and promoting GAG secretion, and are indispensable. Under the synergistic effect of the three, the long-acting retention of modified xanthan gum can provide a stable release environment for liposomes and strontium bromide, avoiding rapid drug loss and improving the effect of the drug; liposomes can accurately deliver chitosan lactate to the injury site, and the ion interaction with strontium bromide synergizes at a local high concentration to strengthen chondrocyte proliferation and matrix secretion; the lubricating protection of xanthan gum and the anti-inflammatory effect of strontium bromide can also reduce the interference of the microenvironment. The combination of the three can effectively improve the degree of cartilage tissue damage repair of the knee joint and greatly improve the effect of cartilage tissue regeneration.

[0045] The above is the preferred embodiment of the present application. It should be noted that for those skilled in the art, without departing from the principles of the present application, several improvements and refinements can be made, which should also be considered within the scope of protection of the present application.

Claims

1. A biological drug solution for injecting into the knee joint to promote cartilage tissue regeneration, characterized in that, By mass percentage, the following components are included: modified xanthan gum 3%-4%, liposome-encapsulated chitosan lactate 1.5%-2.5%, strontium bromide 0.2%-0.6%, disodium hydrogen phosphate 1%-2%, sodium dihydrogen phosphate 1%-2%, and injection water to 100%; the modified xanthan gum is carboxymethylated xanthan gum with an average relative molecular mass of 10-15 million and a carboxymethyl substitution degree of 0.3-0.

6.

2. The biofluid for promoting cartilage tissue regeneration for injection into the knee joint according to claim 1, wherein By mass percentage, the following components are included: modified xanthan gum 3.5%, liposome-encapsulated chitosan lactate 2%, strontium bromide 0.5%, disodium hydrogen phosphate 1.5%, sodium dihydrogen phosphate 1.5%, and injection water to 100%.

3. The biofluid for promoting cartilage tissue regeneration for injection into the knee joint according to claim 1, wherein the biofluid is a solution of hyaluronic acid, chondroitin sulfate, and / or glucosamine. The modified xanthan gum has an average relative molecular mass of 12 million and a carboxymethyl substitution degree of 0.

5.

4. The biofluid for promoting cartilage tissue regeneration for injection into the knee joint according to claim 1, wherein The concentration of lactic acid in the liposome-encapsulated chitosan lactate is 50-100 mmol / L, the liposome is composed of DSPC and cholesterol at a mass ratio of 2:1-4:1, and the particle size is 100-200 nm; the strontium bromide provides a bromide ion concentration of 1-3 mM and a strontium ion concentration of 0.5-2 mM.

5. The biofluid for promoting cartilage tissue regeneration for injection into the knee joint according to claim 4, wherein the biofluid is a solution of hyaluronic acid. The concentration of lactic acid in the liposome-encapsulated chitosan lactate is 80 mmol / L, the liposome is composed of DSPC and cholesterol at a mass ratio of 3:1; the strontium bromide provides a bromide ion concentration of 2 mM and a strontium ion concentration of 1 mM.

6. The biological liquid for promoting cartilage tissue regeneration for injection into the knee joint according to claim 1, wherein The pH value of the biological drug solution is 7.2-7.4, and the osmotic pressure is 280-320 mOsmol / L.

7. The biofluid for promoting cartilage tissue regeneration for injection into the knee joint according to claim 6, wherein The pH value of the biological drug solution is 7.3, and the osmotic pressure is 300 mOsmol / L.

8. The biological liquid for promoting cartilage tissue regeneration for injection into the knee joint according to any one of claims 1 to 7, characterized by, The preparation method of the modified xanthan gum is as follows: xanthan gum is added to a NaOH solution, chloroacetic acid is slowly added after stirring, the pH is adjusted to 7 after further reaction, and then ethanol precipitation and drying are performed to obtain the modified xanthan gum.

9. The biological liquid for promoting cartilage tissue regeneration for injection into the knee joint according to any one of claims 1 to 7, characterized by, The preparation method of the liposome-encapsulated chitosan lactate is as follows: chitosan is first added to a lactic acid solution and stirred until completely dissolved to obtain a chitosan lactate solution; then lecithin and cholesterol are dissolved in chloroform to form a lipid film by rotary evaporation; the chitosan lactate solution is then added, and after water bath, ultrasonic crushing, membrane filtration, and freeze-drying, the liposome-encapsulated chitosan lactate is obtained.

10. The biological liquid for promoting cartilage tissue regeneration for injection into the knee joint according to any one of claims 9, characterized by, The solid-liquid ratio of the chitosan and lactic acid solution is 1:40-50.

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