WO2015062408A1

WO2015062408A1 - Spine implant unit and preparation method thereof

Info

Publication number: WO2015062408A1
Application number: PCT/CN2014/088452
Authority: WO
Inventors: 田芳; 高耀平; 林忠; 陈伟; 张静
Original assignee: 苏州海欧斯医疗器械有限公司; 上海微创骨科医疗科技有限公司
Priority date: 2013-10-31
Filing date: 2014-10-13
Publication date: 2015-05-07
Also published as: CN104586484B; CN104586484A

Abstract

Disclosed is a spine implant unit, comprising an elastic segment, wherein the elastic segment contains a silicone rubber loaded with a drug. Also disclosed is a method for preparing a spine implant unit, comprising the following operation steps: providing a spine implant unit, wherein the spine implant unit comprises an elastic segment; washing and drying the spine implant unit; and injecting liquid silicone rubber containing a drug and a curing agent into the elastic segment, curing at room temperature and forming a silicone rubber loaded with the drug. The spine implant unit has the following functions: relieving pain persistent ailment caused by adhesion and oppression of a focal point, clearing cartilage calcification to break down and absorb same and clearing edema and hypertrophy of yellow ligament and posterior longitudinal ligament.

Description

Spinal implant unit and preparation method thereof

Technical field

The invention relates to the field of medical devices. Specifically, the present invention is applied to the field of orthopedic spinal internal fixation, and relates to a spinal implant unit and a preparation method thereof.

Background technique

Compression caused by adhesions before and after orthopedic surgery is a big problem that plagues doctors and can affect the success rate of surgery. Adhesion before surgery brings difficulty and risk to surgery, and post-operative adhesions cause surgical failure and increase the likelihood of secondary surgery. At the same time, the risk of surgery is increased when the orthopaedic implant needs to be removed. If the implant carries an anti-inflammatory drug and is slowly released to exert an inhibitory effect, the adhesion symptoms can be alleviated or eliminated.

The compression caused by cartilage calcification is also a problem that plagues doctors. The risk of rejection during surgery is high and the possibility of regeneration is high. If the implant contains a drug that breaks down, absorbs, and is slowly released, the compression caused by calcification can be eliminated by treatment.

Inflammation caused by ligamentum flavum, edema of the posterior longitudinal ligament, and compression caused by hypertrophy can also be treated by slow release after the surgery is carried by the implant with anti-inflammatory drugs.

Proper control of pain is extremely important for any post-surgical patient, and pain relief confers significant physiological and psychological benefits to the patient. Effective pain relief not only means smoother and more enjoyable healing (eg, mood, sleep, quality of life, etc.), but it also reduces the onset of chronic pain syndrome.

With the popularization of orthopedic surgery, higher requirements are put forward for improving postoperative rehabilitation. At home and abroad, a lot of research and clinical observations have been carried out on common phenomena such as postoperative infection, adhesion, pain, and cure of the lesion. Various methods have been invented to prevent, alleviate and eliminate these surgical sequelae and improve the quality of surgery.

The effective combination of medical devices and drugs can replace the conventional surgery, injection of a large number of antibacterial, hormone, analgesic and other drugs, and this local targeted drug delivery, the effect is better, side effects smaller. The existing technologies are as follows:

Chinese Patent Application No. 02136332.3, entitled "Drug Release Control Method for Implantable Medical Devices". The invention combines the excellent properties of the inorganic material and the polymer material, and has obvious advantages over the existing pure organic or pure inorganic coating method, and is suitable for protein drugs and other external conditions such as heat and light. Long-term controlled release of sensitive drugs.

"Progress in Biomedical Engineering", Vol. 31, No. 4, 2010, entitled "Preparation of anti-infective coatings on titanium alloy implants and their antibacterial properties in vitro". In this paper, polylactic acid (PDLLA) was used as a carrier to prepare a PDLLA coating containing vancomycin (VCM) on the surface of a titanium alloy implant by solvent-casting. It has been used to inhibit bacterial infections.

Chinese Patent Application No. 201110232842.6, entitled "Anti-Infective Medical Titanium Alloy". The invention adds an appropriate amount of copper element to the chemical composition of the existing medical titanium alloy Ti6Al7Nb, and after special heat treatment, a titanium copper phase is precipitated in the matrix of the medical titanium alloy, thereby imparting antibacterial infection function to the medical titanium alloy. .

Chinese Patent Application No. 200810147918.3, entitled "Antibacterial Bioactive Titanium and Titanium Alloy Implant Materials and Preparation Methods and Applications thereof". The invention uses biomedical grade titanium or titanium alloy as a base material, and analyzes pure chlorine ion-containing substance into deionized water to prepare an electrolyte solution, and applies an anodic oxidation surface modification treatment technique to apply a direct current voltage between the anode and the cathode of the material. -100V, treatment time 1-200 seconds, to obtain bioactive titanium or titanium alloy with bacteriostatic Ti-Cl groups and biologically active Ti-OH groups on the surface, these Ti-Cl groups are hydrolyzed under physiological environment -ClO _x ion with antibacterial and bactericidal action.

Chinese Patent Application No. 200910051827.4, entitled "Drug Coating for Spinal Fixation Screws and Preparation and Application". The invention relates to a pharmaceutical coating and preparation and use for a spinal internal fixation screw having a thickness of 30 to 300 microns. The screws were immersed in PBS dissolved with 0.2 mol/L carbodiimide and 0.05 mol/L N-hydroxysuccinimide for 30 minutes; the bisphosphonates and other drugs were dissolved in distilled water, and the screws were immersed in This solution was obtained in 24 hours. The Drug-coated screws can be used in spinal internal fixation to improve bone quality and reduce fracture risk.

Chinese Patent Application No. 201110088034.7, the title of the invention is "the method of carrying out controlled release of drug-loaded solid drug on the surface of medical device". The invention roughens the surface of the instrument by physical or chemical methods, performs isostatic pressing treatment after drug coating, and firmly binds the drug to the instrument substrate, overcomes the drug falling off caused by direct drug loading on the surface of the device, and achieves the purpose of controlling drug release. .

It can be seen that the prior art performs various treatments on the surface of the implant, such as drug coating, copper ion, anodized surface modification treatment technology, etc. to achieve the purpose of antibacterial, but the drug layer is very thin, and the drug is released. Time is naturally small, and it is impossible to maintain the drug effect for about one year. In addition, because these implants have great friction with bone tissue and instruments during implantation in the human body, there may be a small amount of drug left after the screw enters the bone, and the drug effect will be greatly reduced.

Summary of the invention

The present invention is derived from the applicant's prior Chinese Patent Application No. 201210248135.0, entitled "A Spinal Dynamic Stabilization Implant Unit", the entire contents of which is hereby incorporated by reference in its entirety in its entirety in its entirety in its entirety in its entirety in

In particular, the present invention incorporates a specific therapeutic drug in the silicone rubber portion of the implant unit to prevent postoperative adhesions, infections, and lesion treatment. After the product is implanted into the human body, the silicone rubber drug carrier gradually releases the drug and slowly spreads into the surrounding area of the human body. The problems before the operation and after the operation are truly cured under the medical treatment.

The present invention provides a spinal implant unit comprising an elastic segment, wherein the elastic segment contains a silicone rubber body loaded with a drug.

According to the invention, the spinal implant unit is a dynamic rod.

According to the invention, the drug-loaded silicone rubber body is located in a groove and/or a through hole provided in the elastic section.

According to the present invention, the drug-loaded silicone rubber body is formed by adding a liquid silicone rubber containing a drug and a curing agent to the elastic section and curing at a normal temperature.

According to the invention, the medicament used is a corticosteroid or alpha adrenaline, wherein the corticosteroid is selected from the group consisting of clonidine, fluocinolone, dexamethasone, sulindac, sulfasalazine or a combination thereof.

According to the invention, the medicament used is an anti-inflammatory drug, for example an antibiotic drug.

According to the present invention, the weight ratio of the drug to the liquid silicone rubber is between 10% and 50%, which can be determined by the thickness of the drug-loaded silicone rubber body and the length of time required for the sustained release.

According to the present invention, the daily release rate of the drug can be controlled to be less than 100 μg/kg (patient body weight) depending on the needs of the patient. Those skilled in the art will appreciate that the rate of release depends on the amount of drug used (drug concentration), the thickness and type of the drug-loaded silicone rubber body, and the like, and can be adjusted at will.

According to the invention, the drug-loaded silicone rubber body has a thickness of between 1.5 mm and 5 mm. The thickness herein refers to the dimension of the silicone rubber body substantially in the radial direction of the elastic section. For example, when the silicone rubber body is located in the groove of the elastic section, the thickness thereof is a dimension along the radial depth direction of the groove; when the silicone rubber body is filled in the through hole of the elastic section, the thickness thereof is outside the silicone rubber body. Diameter size. When the silicone rubber body is included in both the groove and the through hole of the elastic section, the silicone rubber bodies located in the groove and the through hole may have different thicknesses, but each of them has a thickness of between 1.5 mm and 5 mm.

Those skilled in the art will appreciate that in addition to the dynamic bars, other spinal implant units of the present invention can use silicone rubber as a drug carrier as long as they contain silicone rubber.

In addition, the present invention has no special requirements for silicone rubber, as long as it can be implanted into the human body for a long period of time, meets safety requirements, and can be cured at room temperature.

The drug amount (drug concentration) of the present invention and the thickness of the drug-loaded silicone rubber body have a certain correlation with the sustained release time, and can be determined according to actual needs. For example, when the drug concentration is constant, the thickness is taken as a large value, and the sustained release time can be prolonged. The sustained release of the drug in the spinal implant unit of the present invention can be as long as three months or six months, or even as long as one year.

The invention also provides a method of preparing a spinal implant unit, comprising the following steps:

Providing a spinal implant unit, the spinal implant unit comprising an elastic segment,

Cleaning and drying the spinal implant unit,

A liquid silicone rubber containing a drug and a curing agent is injected into the elastic segment and cured at a normal temperature to form a drug-loaded silicone rubber body.

According to the invention, a liquid silicone rubber containing a drug and a curing agent is injected into the grooves and/or through holes of the elastic section.

According to the present invention, the weight ratio between the liquid silicone rubber, the drug and the curing agent is 100: (10 to 50): (0.4 to 0.6).

The present invention utilizes silicone rubber in the implant as a pharmaceutical carrier. Silicone rubber is a porous, sorbable material. When a therapeutic drug is dissolved as a biologically active substance, the silica sol molecule can effectively and uniformly adsorb it, and slowly release over time and save. Its corresponding pharmacological properties, while having the characteristics of chemical stability, non-toxic and harmless. Silicone rubber has good penetration and permeability and is an ideal drug release material. The drug utilizes this property of silicone rubber for effective controlled release and slow diffusion through silicone rubber. In addition, the silicone rubber in the implant has a certain thickness, which can be released for a longer period of time than the ordinary implant coating drug, and the silicone rubber body can be regarded as a drug reservoir.

The implant of the invention has anti-adhesion and pain-relieving effects, and the steroid drug, alpha adrenergic or anti-inflammatory drug is dispersed in the form of microparticles in the silicone rubber matrix, and the drug is slowly released, and the release time can be extended to about one year. The method for manufacturing the drug-loaded implant is relatively simple, and only the drug and the silicone rubber are mixed and solidified at a normal temperature, thereby expanding the selection range of the drug.

The beneficial effects of the present invention are embodied in:

The implant has the painful chronic pain caused by the adhesion, compression, etc. of the lesion;

The implant has the function of removing cartilage calcification, causing it to decompose and absorb;

The implant has the function of removing edema and hypertrophy of the ligamentum flavum and the posterior longitudinal ligament.

DRAWINGS

In order to more clearly describe the technical solution of the present invention, a brief description will be made below with reference to the accompanying drawings. It is apparent that these drawings are only some of the specific embodiments described herein. Technical solution of the invention These include but are not limited to these figures.

Figure 1 shows a dynamic rod, wherein 1, the elastic section, 2, the spiral groove, 3, the through hole.

Figure 2 shows the drug-loaded silicone rubber body in the groove of the elastic section, wherein the thickness is B.

detailed description

In order to further understand the present invention, the preferred embodiments of the present invention will be described below in conjunction with the embodiments. These descriptions are merely illustrative of the features and advantages of the spinal implant unit of the present invention and are not intended to limit the scope of the present invention.

Example 1

After the dynamic rod is machined, the oil is cleaned with an ultrasonic cleaner, and then the ultrasonic cleaning machine is used for the final cleaning and drying in the 100,000-level purification workshop. The dynamic rod is shown in FIG. 1 and its specific structure is described in the applicant's prior Chinese Patent Application No. 201110041369.3, entitled "Spine Dynamic Connecting Rod", the entire contents of which are hereby incorporated by reference. And as part of the public content.

Select liquid silicone rubber that can be implanted for a long time. Add the drug (clonidine) to the liquid silicone rubber and mix well. Add the curing agent (0.5wt%) matched with liquid silicone rubber. After mixing well, form a drug. The liquid silicone rubber with the curing agent is transferred into the syringe and injected into the spiral groove of the dynamic rod. Curing at room temperature for 24 hours. The shape of the cured drug-loaded silicone rubber body is as shown in Fig. 2, wherein the thickness B is 3 mm.

Liquid silicone rubber: drug: curing agent = 100:30: 0.5 (weight ratio).

The daily release rate of the drug is controlled to be less than 100 μg/kg (patient weight), and the drug release time can be up to six months.

Example 2

The same as in Example 1, except that the drug was selected from α-adrenalin and the thickness B was 2 mm. Dynamic stick Implanted in the vicinity of the intervertebral disc, sharing the activity and force function of the intervertebral disc to prevent further degeneration of the intervertebral disc. Dynamic rods carry alpha adrenaline and can treat degenerative disc disease including disc herniation.

Example 3

In the same manner as in Example 1, except that the liquid silicone rubber containing the drug and the curing agent was injected into the through hole in the middle of the dynamic bar, the weight ratio of the drug to the liquid silicone rubber was 40%, and the thickness B was 5 mm. The liquid silicone rubber containing the drug and the curing agent is injected into the through hole to increase the drug loading amount, and the drug release time is as long as one year.

The above description of the embodiments is merely for helping to understand the core idea of the present invention. It should be noted that those skilled in the art can make several improvements and modifications to the units and methods of the present invention without departing from the principles of the invention, but such modifications and modifications also fall within the claims of the present invention. Within the scope of protection.

Claims

A spinal implant unit includes an elastic segment, wherein the elastic segment contains a silicone rubber body loaded with a drug.
The spinal implant unit of claim 1 wherein said spinal implant unit is a dynamic rod.
The spinal implant unit of claim 2, wherein the drug-loaded silicone rubber body has a thickness in the range of 1.5 mm to 5 mm.
A spinal implant unit according to claim 1, wherein said drug-loaded silicone rubber body is located in a groove and/or a through hole provided in said elastic section.
The spinal implant unit according to claim 1, wherein the drug is a corticosteroid, alpha adrenergic or an anti-inflammatory drug.
The spinal implant unit of claim 5, wherein the corticosteroid is selected from the group consisting of clonidine, fluocinolone, dexamethasone, sulindac, sulfasalazine or a combination thereof.
A method of preparing a spinal implant unit of claim 1 comprising the following steps:

Providing a spinal implant unit, the spinal implant unit comprising an elastic segment,

Cleaning and drying the spinal implant unit,

A liquid silicone rubber containing a drug and a curing agent is injected into the elastic segment and cured at a normal temperature to form a drug-loaded silicone rubber body.
The method according to claim 7, wherein said liquid silicone rubber containing said drug and said curing agent is injected into said grooves and/or through holes of said elastic section.
The method according to claim 7, wherein the weight ratio of the liquid silicone rubber, the drug and the curing agent is 100: (10 to 50): (0.4 to 0.6).