CN101850154B - Porous bio-ceramic percutaneous implantation device used for topical administration - Google Patents

Abstract

Translated fromChinese

本发明涉及一种用于局部给药的多孔生物陶瓷经皮植入装置。用于局部给药的多孔生物陶瓷经皮植入装置，其特征在于它由多孔陶瓷埋置体和橡胶安全帽组成；多孔陶瓷埋置体成“工”字型，多孔陶瓷埋置体的上端面设有安全帽插入凹槽；橡胶安全帽成“T”型，橡胶安全帽的下部的外形与安全帽插入凹槽的外形相对应，橡胶安全帽的上端边缘部为环扣，橡胶安全帽的下端面设有储药凹槽，橡胶安全帽的下部插入安全帽插入凹槽中，橡胶安全帽的环扣与多孔陶瓷埋置体的上端相扣。本发明结构简单、可长期埋置、使用方便；可实现间断的穿刺注射给药，不经过穿皮，减少痛苦；也可实施连续性输药。

The invention relates to a porous bioceramic percutaneous implantation device for local drug delivery. A porous bioceramic percutaneous implant device for local drug delivery is characterized in that it consists of a porous ceramic embedding body and a rubber safety cap; the porous ceramic embedding body is in the shape of an "I", and the upper part The end face is provided with a safety cap insertion groove; the rubber safety cap is "T" shaped, the shape of the lower part of the rubber safety cap corresponds to the shape of the safety cap insertion groove, the upper edge of the rubber safety cap is a buckle, and the rubber safety cap A drug storage groove is arranged on the lower end surface of the rubber safety cap, the lower part of the rubber safety cap is inserted into the safety cap insertion groove, and the buckle of the rubber safety cap is interlocked with the upper end of the porous ceramic embedding body. The invention has the advantages of simple structure, long-term embedding and convenient use; it can realize intermittent puncture and injection of drug without going through the skin and reduce pain; it can also implement continuous drug delivery.

Description

The porous bio-ceramic percutaneous implantation device that is used for topical

Technical field

The present invention relates to a kind of porous bio-ceramic percutaneous implantation device that is used for topical.

Background technology

Domestic and international state of development: at present, have many chronic and malignant diseases to need the patient part is interrupted or is continued medication, need regularly local chemotherapy and the immunomodulating of insulin injection, tumor etc. like the diabetes patient with severe symptoms.The advantage of embedded type drug-supplying system is: do not have epidermis malabsorption, gastrointestinal degradation and liver " first pass effect ", can reach the body circulation very soon; Drug effect can be avoided the side effect to other tissue in the body in target site, can stablize control blood drug level or targeting moiety drug level for a long time, can improve medicine in partial concentration of focus and utilization rate.Therefore, compare advantage with oral or intravenous systemic administration with uniqueness.Topical mainly is through heeling-in drug-supplying system (Implantable Drug Delivery System; IDDS) realize that Lafarge at first proposed the subdermal implantation pill and obtained the imagination of lasting release for a long time in 1867, nineteen thirty-seven Deansley and Parkes carry out research in the animal body for the first time; Pill is imbedded at subcutaneous tissue; Medicine discharges with certain speed in a long time, keeps effective blood drug concentration, and the range of application of IDDS expands to a plurality of treatments field by originally contraceptive treatments.

Recently, Liu Hongchen has proposed two kinds of new route of administration designs, i.e. artificial growth body whole body drug-supplying systems^[3]With root canal whole body drug-supplying system^[4]These two kinds design Chinese medicines absorb the arrival whole body through tooth implant surrounding bone tissue and natural tooth root periapical tissue respectively, reach the purpose of treatment part and general disease, for new space has been opened up in the application of IDDS system.But this method has been limited to medicine-feeding part, and is not easy to frequent administration operation.

The sorting technique of IDDS has many, but on structure and principle, can be divided into passive embedded type pharmaceutical carrier, active embedded type pharmaceutical carrier and injection supplement type pharmaceutical carrier.The medicament slow release phase of passive embedded type pharmaceutical carrier is limited, and diffusion time, concentration are wayward; Active embedded type pharmaceutical carrier can be controlled time of administration and concentration (metering), but needs retention passages to be in communication with the outside usually, wears skin place easy infection, and is limited through the leather hose holdup time; Though service time, same wayward time of administration and concentration (metering) that injection supplement type thing carrier can prolong carrier.Therefore, develop a kind of can be embedding for a long time, easy to use, the heeling-in drug-supplying system of the kind of administration easy to control, time and concentration becomes the important topic of biomedical material research.

Reference material

1. cold refined, the classification of embedded type drug-supplying system and application, Chinese medicine equipment volume the 5th phase: 5-8. May the 4th in 2007

2. old biography is pretty, and Jiang Xinquan implants the progress of the local chemotherapy of mesenchyma stroma of pouring-in drug sustained release system, foreign medical science stomatology fascicle volume the 1st phase: 21-23 January the 29th in 2002.

3. easy red, Yuan Haoyu, the implant progress of application in treatment of cancer, contemporary Chinese medical magazine volume the 1st phase: 75-76 February the 7th in 2005.

4. Lu Bin, novel pharmaceutical formulation and new technique [M]. second edition, Beijing: People's Health Publisher, 2005:1-2.

5. Jia Wei, Gao Wenyuan, Qiu Mingfeng. medicine controlled releasing novel form [M]. Beijing: the .2005:1-300 of Chemical Industry Press.

6. Liu Hong minister, the design [J] of canine implant whole body drug-supplying system. oral and maxillofacial surgery prosthodontics magazine, 2006,7 (4): 291-292.

7. Liu Hong minister, root canal whole body administration hypothesis [J]. Chinese gerodontics magazine, 2007,5 (1): 2-3.

8.Matschke?C，Isele?U，Fahr?A，et?al.Sustainedrelease?injectables?formed?insitu?and?their?potential?use?for?veterinary?products[J].J?ControlRel，2002，85(1-3)：1-15。

9.Hatefi?A，Amsden?B.Biodegradable?injectable?insitu?forming?drug?deliverysystems[J].J?ControlRel，2002，80：9-28。

Summary of the invention

The object of the present invention is to provide a kind of porous bio-ceramic percutaneous implantation device that is used for topical simple in structure, easy to use.

To achieve these goals, technical scheme that the present invention adopts is: be used for the porous bio-ceramic percutaneous implantation device of topical, it is characterized in that it is made up of embedding body of porous ceramics and rubber safety helmet; The embedding body of porous ceramics becomes " worker " font, and the upper surface of the embedding body of porous ceramics is provided with safety helmet and inserts groove, and the material of the embedding body of porous ceramics is an osmosis type hydroxyapatite porous ceramics; The rubber safety helmet becomes T-shape; The profile of the bottom of rubber safety helmet is corresponding with the profile that safety helmet inserts groove; The upper end-face edge portion of rubber safety helmet is a latch closure; The lower surface of rubber safety helmet is provided with the drug storage groove, and the bottom of rubber safety helmet is inserted safety helmet and inserted in the groove, and the upper end of the latch closure of rubber safety helmet and the embedding body of porous ceramics interlocks.

The rubber safety helmet is provided with tube for transfusion, and rubber safety helmet and tube for transfusion fuse, and tube for transfusion is connected with the drug storage groove.

The preparation of the embedding body of porous ceramics:

1). the preparation of hydroxylapatite powder: 1.. the preparation of pure ha powder: get Ca (OH)₂, process suspension with distilled water, the concentration of suspension is 3.9wt%; Above-mentioned suspension is inserted in the water bath with thermostatic control, and bath temperature is 40.0 ℃, simultaneously suspension is stirred, and obtains Ca (OH)₂Suspension; Get dense H₃PO₄Be mixed with H₃PO₄Weak solution, H₃PO₄The concentration of weak solution is 3.5wt%; With H₃PO₄Weak solution dropwise is added drop-wise to Ca (OH)₂In the suspension, dripping speed is 120 droplets/minute; Simultaneously, keep water bath heating temperature and stirring; After waiting to dropwise, continue to stir 15 minutes, regulate pH value to 9～11, regulated the back restir 1 hour, take out, processed the sol solutions of hydroxyapatite with dilute NaOH solution; The sol solutions of gained was left standstill 24 hours, with the clear water sucking-off on top, dry in baking oven behind the gel sucking filtration of bottom then, make unformed hydroxyapatite; The unformed hydroxyapatite of gained is levigate, then 900 ℃ of insulations 1.5 hours, obtain the hydroxyapatite of high-crystallinity; With hydroxyapatite is medium with water, and ball milling 24 hours after the oven dry, obtains the pure ha powder, and it is for use to put into exsiccator;

2.. the mass ratio by unformed hydroxyapatite, water, silver nitrate is 1: 0.08: 10, chooses unformed hydroxyapatite, water and silver nitrate; Unformed hydroxyapatite and silver nitrate added be made into suspension in the entry, heat to 50 ℃ continuous stirring 3 hours; Filter then, diafiltration to solution does not have nitrate ion, dry, 900 ℃ of calcinings; Be medium ball milling 24 hours then with the dehydrated alcohol, the dry argentiferous hydroxylapatite powder that obtains;

2). the preparation of bio-vitric high temperature adhesive:

With quartz sand, calcium carbonate, calcium hydrogen phosphate and natrium carbonicum calcinatum is raw material, according to Na₂O 18～25wt%, CaO 18～25wt%, P₂O₅8～10wt%, SiO₂40～48% prescription batching, mix homogeneously is put into alumina crucible, in 1450 ℃ of fusings of silicon molybdenum stove 1.5 hours, takes out shrend with crucible tongs then; The glass frit of shrend with Achates grinder porphyrize, is put into ball grinder again and was added the dehydrated alcohol ball milling 24 hours, take out filter, drying, obtain the bio-vitric high temperature adhesive;

3). the pretreatment of carbon dust:

At first, carbon dust is carried out intensive drying, add the oleic acid of carbon dust quality 0.2-1.0wt%, carried out the dry bulb mill together 3 hours; Then carbon dust is carried out sieve classification, drying obtains pretreated carbon dust;

4). the pretreatment of hydroxyapatite porcelain:

By the shared mass percent of each raw material be: pure ha powder 75～95wt%, bio-vitric high temperature adhesive 5～25wt% chooses pure ha powder and bio-vitric high temperature adhesive;

Pure ha powder and bio-vitric high temperature adhesive are mixed; Carry out intensive drying, add the oleic acid of pure ha powder and bio-vitric high temperature adhesive gross mass 0.2-1.0wt% then, carried out the dry bulb mill together 3 hours; Drying obtains pretreated hydroxyapatite porcelain;

5). the preparation of hot pressing casting cake:

Exsiccant pretreated hydroxyapatite porcelain 40～60vol% is mixed with the pretreated carbon dust of 60～40vol%,, obtain mixed powder through 2 hours mixings of dry bulb mill, for use; Press mixed powder 40～60vol%, melting wax liquation 60～40vol%, choose mixed powder and melting wax liquation; By oleic addition is mixed powder quality 0.2～1.0wt%, chooses oleic acid; With above-mentioned mixed powder under agitation, add in the melting wax liquation, splash into oleic acid, obtain slip; Slurry is poured on and solidifies formation gatch in back on the cold steel plate, and gatch is displayed more than 72 hours subsequent use;

6). hot-injection molding:

The gatch of depositing is put into Hot-pressed injector hot pressing form " worker " font, 85～110 ℃ of control temperature, after treating fully to melt, evacuation stirs the degassing, and briquetting pressure is controlled at 0.25-0.30MPa, obtains the base substrate of hot-injection molding;

7). dewaxing, plastic removal and biscuiting:

The base substrate of hot-injection molding is imbedded in the fire-resistant saggar of containing hydroxylapatite powder, put into silicon carbide rod furnace and dewax, arrange carbon and biscuiting, programming rate＜2 ℃/min, in 700 ℃～850 ℃ insulation 1.5～2.5h, furnace cooling obtains unglazed base substrate;

8). surface-sealing is handled:

Unglazed base substrate is taken out, fall the hydroxy apatite powder of billet surface clearly, spray deashing with high pressure air then with hairbrush, for use; Mass ratio by argentiferous hydroxylapatite powder and water is 1: 1; Choose argentiferous hydroxylapatite powder and water; Argentiferous hydroxylapatite powder adding distil water is mixed with argentiferous hydroxylapatite powder slurry; Be stained with argentiferous hydroxylapatite powder slurry with spread pen, billet surface and contact skin are carried out sealing of hole with the part of stretching out skin, obtain the biscuiting base substrate of sealing of hole after the drying;

9). burn till:

The biscuiting base substrate that drying is good is put into silicon carbide rod furnace and is burnt till, and 5～10 ℃/min of programming rate is warming up to 1220 ℃ ofinsulations 2 hours, and the furnace cooling that cuts off the power supply then obtains osmosis type hydroxyapatite porous ceramics, i.e. the embedding body of porous ceramics.

Principle of the present invention is to utilize the diffusion of osmosis type hydroxyapatite porous ceramics as route of administration; Aperture through control osmosis type hydroxyapatite porous ceramics in the preparation process; Realize that liquid drug can diffuse in the body, and antibacterial and virus can not get into intravital purpose; Utilize osmosis type hydroxyapatite porous ceramics and the epithelial tissue can good combination; Form the bonding state of similar gingiva and tooth; Can guarantee that implantation body for a long time, stably implants; Skin and implant (being the embedding body of porous ceramics) interface can be because of inflammation lose efficacy, thus can through external be interrupted or continue carry out topical.This device adopts osmosis type hydroxyapatite porous ceramics (or to claim the porous hydroxyapatite bioceramic; Or title hydroxyapatite porous ceramics) preparation, its Kong Duowei intercommunicating pore has suitable permeability; Can implant subcutaneously for a long time, play the effect of inside and outside liquid (medicine) diffusion admittance of connector.Through the aperture of control osmosis type hydroxyapatite porous ceramics, reach the demand of external localized delivery different pharmaceutical; Control the communication aperture of osmosis type hydroxyapatite porous ceramics and wear the rubber safety helmet through strictness, reach the purpose that prevents that antibacterial and virus from invading.

The invention has the beneficial effects as follows:

1. simple in structure, can be embedding for a long time (said is 2-8 for a long time), easy to use.

2. can realize the puncture injection administration that is interrupted,, reduce painful without wearing skin; Also can implement the seriality loading.

3. the embedding body of porous ceramics stretches out near the surface of skin by silver-containing antibacterial hydroxylapatite ceramic slurry sealing of hole, makes embedding body of porous ceramics and contact skin and the part of stretching out skin have antibacterial functions.

Description of drawings

Fig. 1 is the cross sectional representation that is used for the porous bio-ceramic percutaneous implantation device of topical.

Fig. 2 is the structural representation of the rubber safety helmet of band tube for transfusion.

Fig. 3 is the micro-structure diagram of the osmosis type hydroxyapatite porous ceramics of the compound preparation method preparation of employing hot pressing notes-pore creating material.

Among the figure: 1-subcutaneous tissue, the embedding body of 2-porous ceramics, 3-puncture injection administration district, 4-drug storage district, 5-rubber safety helmet, 6-tube for transfusion.

The specific embodiment

Like Fig. 1, shown in Figure 2, be used for the porous bio-ceramic percutaneous implantation device of topical, it is made up of with rubber safety helmet 5 the embedding body 2 of porous ceramics; 2 one-tenth " worker " fonts of the embedding body of porous ceramics; The upper surface of the embedding body 2 of porous ceramics (being arranged in the end outside the subcutaneous tissue 1) is provided with safety helmet and inserts groove (Fig. 1 of present embodiment; The cross section that safety helmet inserts groove is trapezoidal), the material of the embedding body 2 of porous ceramics is an osmosis type hydroxyapatite porous ceramics; 5 one-tenth T-shapes of rubber safety helmet; The profile of the bottom of rubber safety helmet 5 is corresponding with the profile that safety helmet inserts groove (or to be claimed to match; The bottom of rubber safety helmet 5 can tightly be inserted safety helmet and inserted in the groove); The upper end-face edge portion of rubber safety helmet 5 is latch closure (being annular the button), and the lower surface of rubber safety helmet 5 is provided with drug storage groove (the drug storage groove is drug storage district 4, and the top of drug storage groove is puncture injection administration district 3); The bottom of rubber safety helmet 5 is inserted safety helmet and is inserted in the groove, and the upper end of the embedding body 2 of the latch closure of rubber safety helmet 5 and porous ceramics interlocks.During use, the bottom of the embedding body 2 of porous ceramics is imbedded in the subcutaneous tissue 1, and the upper surface of the embedding body 2 of porous ceramics is positioned at outside the subcutaneous tissue 1.Medicine is injected in the drug storage groove by syringe puncture injection administration district 3, and perhaps the rubber safety helmet is provided with tube for transfusion 6, and rubber safety helmet and tube for transfusion 6 fuse, and tube for transfusion 6 is connected with the drug storage groove, and medicine is injected in the drug storage groove by tube for transfusion 6.Rubber safety helmet 5 is processed by elastic silicone rubber.

The external diameter of the embedding body ofporous ceramics 2 bottoms is greater than the external diameter of the embedding body ofporous ceramics 2 upper ends.The bottom of the embeddingbody 2 of porous ceramics is a revolving body, and the top of the embeddingbody 2 of porous ceramics is revolving body.The upper surface of the embeddingbody 2 of porous ceramics and the above surface compact of cervical region prevent that medicine from spreading to the epidermis direction; The embeddingbody 2 inner porous of porous ceramics are convenient to medicine and are spread downwards.

One, the preparation of the embedding body of porous ceramics:

(1), the primary characteristic of osmosis type hydroxyapatite porous ceramics is the characteristic that its porous and hole are interconnected, and further is to control its aperture, pore structure, pore size distribution and permeability, to satisfy the demand that different pharmaceutical discharges.In addition, for the batch process that realizes the embedding body of porous ceramics (or claim drug controlled-release body, or claim the porous sustained-release carrier) and the accurate control of size, also must searching can satisfy the method for preparing of above-mentioned requirements simultaneously.The present invention adopts following two kinds of method for preparinies that satisfy above-mentioned requirements.

1. the compound preparation method of hot pressing notes-pore creating material:

Hot-injection molding is the very strong technology of a kind of practicality, is the effective ways of preparation high reliability, complicated shape ceramic component.It has following distinguishing feature: the ceramic part of (1) plastic various complicated shapes and size; (2) even the peculiar blank of shape can guarantee that all densification, even is formed at each position in the blank, the molding blank defective is few; (3) no dust, the harm of noise has improved working environment greatly and has reduced labor intensity; (4) operating pressure is 490～588kPa, only reaches 1/10～1/20 of same size powder die pressing product, and the hot-injection molding machine is simple in structure, and is easy to maintenance, and cost is low, invest little, output is high, the characteristics of constant product quality; (5) can carry out machined (car, mill, dig, mill, boring, saw etc.) to base substrate, thus cancellation or reduce sintering after processing.

The base substrate of hot-injection molding finally obtains product through de-waxing and sintering; Through control paraffin content and sintering temperature; The porous ceramics in ceramic of compact or the different porosity and aperture can be obtained,, fine and close relatively pottery can be obtained if improve sintering temperature or prolong temperature retention time.This method is that hot-injection molding method and pore creating material forming method are combined; The carbon dust of employing different-grain diameter or starch are as pore creating material; Add in the hot pressing material feeding slurry; Through the paraffin content of control slip, the content and the distribution of particles of pore creating material,, control pore structure, aperture, pore size distribution and the porosity of the embedding body of porous ceramics in conjunction with the control of firing temperature.

2. isostatic cool pressing-pore creating material-turning method for preparing

Isostatic cool pressing-turning forming method is a kind of method for preparing precision, high-strength revolving body pottery parts, is suitable for the production of precise ceramic component in batches.The carbon dust of employing different-grain diameter or starch add in the isostatic cool pressing powder body as pore creating material, through the cold isostatic compaction bar, are processed into required revolving body base substrate through turning then, obtain porous ceramic bodies through super-dry, row's carbon and sintering.Through bonding agent, carbon dust or contents of starch and the distribution of particles in the control ceramic powder, in conjunction with the control of firing temperature, pore structure, aperture, pore size distribution and the porosity of may command porous ceramic bodies (the embedding body of porous ceramics).

(2), the hole sealing technology of the embedding surface of porous ceramics

Because it is fine and close that the embedding body of porous ceramics stretches out part (promptly being positioned at the part outside the subcutaneous tissue 1) surface requirements of body surface, and the implant part of the embedding body of porous ceramics (promptly being positioned at the part of subcutaneous tissue 1) also need be implemented directed diffusion administration to internal lesions.Therefore; Must carry out surface-sealing as required to the part surface that the embedding body of porous ceramics stretches out body surface; Its method is: the bad body to molding carries out biscuiting, row's carbon, and the row's of treating carbon is mixed with slurry with argentiferous hydroxylapatite powder and water after accomplishing; With spread pen its porous surface is made the shallow-layer sealing of hole, dry back high temperature burns till.In addition, the embedding body of porous ceramics is stretched out near the surface the skin,, make embedding body of porous ceramics and contact skin and the part of stretching out skin have antibacterial functions with argentiferous hydroxyapatite slurry sealing of hole.

(3), the shaped design of the embedding body subdermal implantation part of porous ceramics

In order to satisfy the administration requirements of patient's different parts, different depth, can the porous body shape of subcutaneous part be designed, but be generally the complete body of revolution shape, do not contain other accessory.

Two, the preparation embodiment of the embeddingbody 2 of porous ceramics:

Adopt the compound preparation method of hot pressing notes-pore creating material to prepare the embedding body of porous ceramics.

1. the preparation of hydroxylapatite powder: comprise the preparation of pure ha powder and argentiferous hydroxylapatite powder.Adopt sol-gel process.

1). the preparation of pure ha powder: the raw material of sol-gel process synthesizing hydroxylapatite is calcium hydroxide (analytical pure,>=95%) and SPA (analytical pure,>=85%), gets Ca (OH)₂(analytical pure) processed suspension with distilled water, and the concentration of suspension is 3.9wt%; Above-mentioned suspension is inserted in the water bath with thermostatic control, and bath temperature is 40.0 ℃, simultaneously suspension is stirred, and obtains Ca (OH)₂Suspension; Get dense H₃PO₄(analytical pure) is mixed with H₃PO₄Weak solution, H₃PO₄The concentration of weak solution is 3.5wt%; With H₃PO₄Weak solution dropwise is added drop-wise to Ca (OH)₂In the suspension, dripping speed is 120 droplets/minute; Simultaneously, keep water bath heating temperature and stirring; After waiting to dropwise, continue to stir 15 minutes, let material in the solution fully react after, regulate pH value to 9～11 with dilute NaOH solution, regulated the back restir 1 hour, take out, processed the sol solutions of hydroxyapatite; The sol solutions of gained was left standstill 24 hours, with the clear water sucking-off on top, dry in baking oven behind the gel sucking filtration of bottom then, make unformed hydroxyapatite; The unformed hydroxyapatite of gained is levigate, then 900 ℃ of insulations 1.5 hours, obtain the hydroxyapatite of high-crystallinity; The hydroxyapatite that uses sol-gel process to make is medium with water, and ball milling 24 hours after the oven dry, obtains the pure ha powder, and it is for use to put into exsiccator.

2). the preparation of argentiferous hydroxylapatite powder is slightly different, is 1: 0.08: 10 by the mass ratio of unformed hydroxyapatite, water, silver nitrate, chooses unformed hydroxyapatite, water and silver nitrate; The unformed hydroxyapatite hydroxyapatite of high-temperature calcination (promptly without) and silver nitrate added be made into suspension (silver adds in the suspension with certain density silver nitrate form) in the entry; Heat to 50 ℃, continuous stirring 3 hours is filtered then; Diafiltration to solution does not have nitrate ion; Dry, 900 ℃ of calcinings are medium ball milling 24 hours then with the dehydrated alcohol, the dry argentiferous hydroxylapatite powder that obtains.

2. the preparation of bio-vitric high temperature adhesive (or claiming biological glass powder):

With quartz sand, calcium carbonate, calcium hydrogen phosphate and natrium carbonicum calcinatum is raw material, according to Na₂O 18～25wt%, CaO 18～25wt%, P₂O₅8～10wt%, SiO₂40～48% prescription batching, mix homogeneously is put into alumina crucible, in 1450 ℃ of fusings of silicon molybdenum stove 1.5 hours, takes out shrend with crucible tongs then; The glass frit of shrend with Achates grinder porphyrize, is put into ball grinder again and was added the dehydrated alcohol ball milling 24 hours, take out filter, drying, obtain the bio-vitric high temperature adhesive, for use.

3. the pretreatment of carbon dust:

At first, carbon dust is carried out intensive drying, add the oleic acid of carbon dust quality 0.2～1.0wt%, carried out the dry bulb mill together 3 hours; Then carbon dust is carried out sieve classification, drying obtains pretreated carbon dust, stores for use.

4. the pretreatment of hydroxyapatite porcelain:

By the shared mass percent of each raw material be: pure ha powder 75～95wt%, bio-vitrichigh temperature adhesive 5～25wt% chooses pure ha powder and bio-vitric high temperature adhesive;

Pure ha powder and bio-vitric high temperature adhesive (or claiming biological glass powder) are mixed; Carry out intensive drying, add the oleic acid of pure ha powder and bio-vitric high temperature adhesive gross mass 0.2～1.0wt% then, carried out the dry bulb mill together 3 hours; Again the porcelain powder is carried out sieve classification; Drying obtains pretreated hydroxyapatite porcelain, stores for use.

5. the preparation of hot pressing casting cake:

Exsiccant pretreated hydroxyapatite porcelain 40～60vol% is mixed with the pretreated carbon dust of 60～40vol%,, obtain mixed powder through 2 hours mixings of dry bulb mill, for use; Press mixed powder 40～60vol%, melting wax liquation 60～40vol%, choose mixed powder and melting wax liquation; By oleic addition is mixed powder quality 0.2～1.0wt%, chooses oleic acid; Above-mentioned mixed powder under stirring fast, is slowly added in the melting wax liquation, splash into oleic acid, regulate the flowability of slip, obtain slip; The control slip can form continuous flow line (with Glass rod lixiviate slip when flowing; Slip trickles into line along Glass rod) be the maximum adding quantity of mixed powder; In addition, according to of the requirement of the embedding body of porous ceramics to the porosity, can be through regulating carbon dust and slurry paraffin content; Regulate the porosity, the pore size distribution that grain warp through regulating carbon dust and paraffin content are regulated the embedding body of porous ceramics; Slurry is poured on and solidifies formation gatch in back on the cold steel plate, and gatch is through displaying more than 72 hours, and it is more even that wax and powder body are merged, and changes hot pressing again over to and annotate operation.

6. hot-injection molding:

The gatch of depositing is put into Hot-pressed injector hot pressing form " worker " font, 85～110 ℃ of control temperature, after treating fully to melt, evacuation stirs the degassing, and briquetting pressure is controlled at 0.25-0.30MPa, obtains the base substrate of hot-injection molding.

7. dewaxing, plastic removal and biscuiting:

The base substrate of hot-injection molding is imbedded in the fire-resistant saggar of containing hydroxylapatite powder, put into silicon carbide rod furnace and dewax, arrange carbon and biscuiting, programming rate＜2 ℃/min, in 700 ℃～850 ℃ insulation 1.5～2.5h, furnace cooling obtains unglazed base substrate.

8. surface-sealing is handled:

Unglazed base substrate is taken out, fall the hydroxy apatite powder of billet surface clearly, spray deashing with high pressure air then with hairbrush, for use.Mass ratio by argentiferous hydroxylapatite powder and water is 1: 1; Choose argentiferous hydroxylapatite powder and water; The argentiferous hydroxylapatite powder slurry of argentiferous hydroxylapatite powder adding distil water preparation is stained with argentiferous hydroxylapatite powder slurry with spread pen, and the part (promptly with contact skin and the part of stretching out skin) that billet surface need be sealed is carried out sealing of hole; Wait after the drying to burn, obtain dry good biscuiting base substrate.

9. burn till:

The biscuiting base substrate that drying is good is put into silicon carbide rod furnace and is burnt till, and 5～10 ℃/min of programming rate is warming up to 1220 ℃ ofinsulations 2 hours, and the furnace cooling that cuts off the power supply then obtains osmosis type hydroxyapatite porous ceramics, i.e. the embedding body of porous ceramics.

The key technical indexes of the embedding body of porous ceramics:

Biocompatibility: the requirement of the GB/T16886 series standard that is up to state standards;

Pore footpath: 20-500nm;

Under the pressure of 6000Pa to the infiltration rate of 25 ℃ of pure water: 20-500 μ l/cm²S;

Transmitance to antibacterial: 0%.

The microstructure of osmosis type hydroxyapatite porous ceramics (the embedding body of porous ceramics):

Fig. 3 is the embedding body of porous ceramics that adopts the compound preparation method preparation of hot pressing notes-pore creating material; Through the content and the sintering temperature of control pore creating material, can be in the aperture of regulating osmosis type hydroxyapatite porous ceramics in a big way 20nm-0.1 μ m) and pore-size distribution (aperture:.

Claims (4)

Translated fromChinese

1.用于局部给药的多孔生物陶瓷经皮植入装置，其特征在于它由多孔陶瓷埋置体(2)和橡胶安全帽(5)组成；多孔陶瓷埋置体(2)成“工”字型，多孔陶瓷埋置体(2)的上端面设有安全帽插入凹槽，多孔陶瓷埋置体(2)的材料为渗透型羟基磷灰石多孔陶瓷；橡胶安全帽(5)成“T”型，橡胶安全帽(5)的下部的外形与安全帽插入凹槽的外形相对应，橡胶安全帽(5)的上端边缘部为环扣，橡胶安全帽(5)的下端面设有储药凹槽，橡胶安全帽(5)的下部插入安全帽插入凹槽中，橡胶安全帽(5)的环扣与多孔陶瓷埋置体(2)的上端相扣；1. A porous bioceramic percutaneous implant device for local administration, characterized in that it consists of a porous ceramic embedding body (2) and a rubber safety cap (5); " font, the upper end surface of the porous ceramic embedding body (2) is provided with a safety cap insertion groove, and the material of the porous ceramic embedding body (2) is permeable hydroxyapatite porous ceramics; the rubber safety cap (5) is formed "T" type, the profile of the bottom of the rubber safety cap (5) corresponds to the profile of the insertion groove of the safety cap, the upper edge of the rubber safety cap (5) is a buckle, and the lower end surface of the rubber safety cap (5) is set There is a drug storage groove, the lower part of the rubber safety cap (5) is inserted into the safety cap insertion groove, and the ring buckle of the rubber safety cap (5) is interlocked with the upper end of the porous ceramic embedding body (2);多孔陶瓷埋置体的制备：Preparation of Porous Ceramic Embedded Body:1).羟基磷灰石粉的制备：①.纯羟基磷灰石粉的制备：取Ca(OH)₂，用蒸馏水制成悬浮液，悬浮液的浓度为3.9wt％；将上述悬浮液置入恒温水浴中，水浴温度为40.0℃，同时对悬浮液加以搅拌，得到Ca(OH)₂悬浮液；取浓H₃PO₄配制成H₃PO₄稀溶液，H₃PO₄稀溶液的浓度为3.5wt％；将H₃PO₄稀溶液逐滴滴加到Ca(OH)₂悬浮液中，滴速为120滴/分；同时，保持水浴加热温度并搅拌；待滴加完毕后，继续搅拌15分钟，用稀NaOH溶液调节pH值到9～11，调节好后再搅拌1小时，取出，制成了羟基磷灰石的溶胶液；将所得的溶胶液静置24小时，然后将上部的清水吸出，下部凝胶抽滤后，在烘箱中干燥，制得无定型羟基磷灰石；将所得的无定型羟基磷灰石磨细，然后在900℃保温1.5小时，得到高结晶度的羟基磷灰石；将高结晶度的羟基磷灰石以水为介质，球磨24小时，烘干后，得到纯羟基磷灰石粉，放入干燥器中待用；1). Preparation of hydroxyapatite powder: ①. Preparation of pure hydroxyapatite powder: take Ca(OH)₂ and make a suspension with distilled water, the concentration of the suspension is 3.9wt%; put the above suspension Put it into a constant temperature water bath, the temperature of the water bath is 40.0°C, and stir the suspension at the same time to obtain a Ca(OH)₂ suspension; take concentrated H₃ PO₄ to prepare a H₃ PO₄ dilute solution, and the concentration of the H₃ PO₄ dilute solution is 3.5wt%; add H₃ PO₄ dilute solution dropwise to Ca(OH)₂ suspension at a rate of 120 drops/min; at the same time, keep the water bath heating temperature and stir; after the dropwise addition is completed, continue Stir for 15 minutes, adjust the pH value to 9-11 with dilute NaOH solution, stir for 1 hour after adjustment, take it out, and make a sol solution of hydroxyapatite; let the obtained sol solution stand for 24 hours, and then put the upper part The clear water was sucked out, the lower gel was suction-filtered, and then dried in an oven to obtain amorphous hydroxyapatite; the obtained amorphous hydroxyapatite was ground, and then kept at 900°C for 1.5 hours to obtain high-crystallinity hydroxyapatite Hydroxyapatite: high crystallinity hydroxyapatite is ball milled in water for 24 hours and dried to obtain pure hydroxyapatite powder, which is put into a desiccator for use;②.按无定型羟基磷灰石、水、硝酸银的质量比为1∶0.08∶10，选取无定型羟基磷灰石、水和硝酸银；将无定型羟基磷灰石和硝酸银加入水中配成悬浮液，加温至50℃，连续搅拌3小时，然后过滤，滤洗至溶液无硝酸根离子，干燥、900℃煅烧，然后以无水乙醇为介质球磨24小时，干燥获得含银羟基磷灰石粉；②. According to the mass ratio of amorphous hydroxyapatite, water and silver nitrate as 1:0.08:10, select amorphous hydroxyapatite, water and silver nitrate; add amorphous hydroxyapatite and silver nitrate to water to prepare into a suspension, heated to 50°C, stirred continuously for 3 hours, then filtered, filtered and washed until the solution was free of nitrate ions, dried, calcined at 900°C, and then ball-milled with absolute ethanol for 24 hours, dried to obtain silver-containing hydroxyphosphorus limestone powder;2).生物玻璃高温粘接剂的制备：2). Preparation of bioglass high temperature adhesive:以石英砂、碳酸钙、磷酸氢钙和无水碳酸钠为原料，按照Na₂O 18～25wt％、CaO 18～25wt％、P₂O₅ 8～10wt％、SiO₂ 40～48％的配方配料，混合均匀，放入氧化铝坩锅，于硅钼炉1450℃熔化1.5小时，然后用坩锅钳取出水淬；将水淬的玻璃熔块用玛瑙研磨机研细，再放入球磨罐中加无水乙醇球磨24小时，取出过滤、干燥，得到生物玻璃高温粘接剂；Using quartz sand, calcium carbonate, calcium hydrogen phosphate and anhydrous sodium carbonate as raw materials, according to the formula of Na₂ O 18-25wt%, CaO 18-25wt%, P₂ O₅ 8-10wt%, SiO₂ 40-48% Mix the ingredients evenly, put them into an alumina crucible, melt in a silicon-molybdenum furnace at 1450°C for 1.5 hours, then take out the water quenching with crucible tongs; grind the water quenched glass frit finely with an agate grinder, and then put it into a ball mill jar Add absolute ethanol to ball mill for 24 hours, take out, filter and dry to obtain bioglass high-temperature adhesive;3).碳粉的预处理：3). Pretreatment of carbon powder:首先，将碳粉进行充分干燥，加入碳粉质量0.2-1.0wt％的油酸，一起进行干球磨3小时；然后对碳粉进行筛分分级，干燥，得到预处理的碳粉；First, fully dry the carbon powder, add 0.2-1.0 wt% oleic acid of the carbon powder mass, and carry out dry ball milling together for 3 hours; then sieve and classify the carbon powder, dry it, and obtain the pretreated carbon powder;4).羟基磷灰石瓷料的预处理：4). Pretreatment of hydroxyapatite porcelain:按各原料所占质量百分比为：纯羟基磷灰石粉75～95wt％，生物玻璃高温粘接剂5～25wt％，选取纯羟基磷灰石粉和生物玻璃高温粘接剂；According to the mass percentage of each raw material: pure hydroxyapatite powder 75-95wt%, bio-glass high-temperature adhesive 5-25wt%, select pure hydroxyapatite powder and bio-glass high-temperature adhesive;将纯羟基磷灰石粉和生物玻璃高温粘接剂混合，进行充分干燥，然后加入纯羟基磷灰石粉和生物玻璃高温粘接剂总质量0.2-1.0wt％的油酸，一起进行干球磨3小时，干燥，得到预处理后的羟基磷灰石瓷料；Mix pure hydroxyapatite powder and bioglass high-temperature adhesive, fully dry, then add pure hydroxyapatite powder and bioglass high-temperature adhesive oleic acid with a total mass of 0.2-1.0wt%, and perform dry ball milling together 3 hours, dry to obtain the pretreated hydroxyapatite ceramic material;5).热压注蜡饼的制备：5). Preparation of hot-pressed wax injection cake:将干燥的预处理后的羟基磷灰石瓷料40～60vol％与60～40vol％预处理的碳粉混合，经干球磨2小时混匀，得到混合粉料，待用；按混合粉料40～60vol％、熔化的石蜡熔液60～40vol％，选取混合粉料和熔化的石蜡熔液；按油酸的加入量为混合粉料质量0.2～1.0wt％，选取油酸；将上述混合粉料在搅拌下，加入熔化的石蜡熔液中，滴入所选取油酸，得到浆料；浆料倒在冷的钢板上凝固后形成蜡饼，蜡饼陈放72小时以上备用；Mix 40-60vol% of the dried pretreated hydroxyapatite ceramic material with 60-40vol% pretreated carbon powder, and mix them evenly through dry ball milling for 2 hours to obtain a mixed powder for use; press the mixed powder for 40 ～60vol%, melted paraffin melt 60～40vol%, choose mixed powder and melted paraffin melt; According to the add-on of oleic acid is mixed powder quality 0.2～1.0wt%, choose oleic acid; Above-mentioned mixed powder Stir the material into the melted paraffin wax solution, drop in the selected oleic acid to obtain a slurry; pour the slurry on a cold steel plate to solidify to form a wax cake, and leave the wax cake for more than 72 hours for later use;6).热压注成型：6).Hot press injection molding:将存放的蜡饼放入热压注机中热压注成“工”字型，控制温度85～110℃，待充分熔化后，抽真空搅拌脱气，成型压力控制在0.25-0.30MPa，得到热压注成型的坯体；Put the stored wax cake into a hot-press injection machine and hot-press inject it into an "I" shape. The temperature is controlled at 85-110°C. After it is fully melted, it is vacuumed and stirred for degassing. The molding pressure is controlled at 0.25-0.30MPa to obtain Hot press injection molded green body;7).脱蜡、排碳和素烧：7). Dewaxing, carbon removal and bisque firing:将热压注成型的坯体埋入盛羟基磷灰石粉的耐火匣钵中，放入硅碳棒炉中进行脱蜡、排碳和素烧，升温速度＜2℃/min，于700℃～850℃保温1.5～2.5h，随炉冷却，得到素烧的坯体；Embed the hot-pressed injection molded body in a refractory sagger containing hydroxyapatite powder, put it into a silicon carbide rod furnace for dewaxing, carbon removal and bisque firing, the heating rate is <2°C/min, at 700°C ～850℃ heat preservation for 1.5～2.5h, cooling with the furnace to obtain biscuit body;8).表面封孔处理：8). Surface sealing treatment:将素烧的坯体取出，用毛刷清掉素烧的坯体表面的羟基磷灰石粉体，然后用高压压缩空气喷射清灰，待用；按含银羟基磷灰石粉与蒸馏水的质量比为1∶1，选取含银羟基磷灰石粉和蒸馏水，含银羟基磷灰石粉加蒸馏水配制成含银羟基磷灰石粉浆料，用排笔沾含银羟基磷灰石粉浆料，对素烧的坯体表面与皮肤接触和伸出皮肤的部分进行封孔，干燥后得到封孔的素烧坯体；Take out the biscuit body, remove the hydroxyapatite powder on the surface of the biscuit body with a brush, then use high-pressure compressed air to spray the dust, and set it aside; press the silver-containing hydroxyapatite powder and distilled water The mass ratio is 1:1, select silver-containing hydroxyapatite powder and distilled water, add silver-containing hydroxyapatite powder and distilled water to prepare silver-containing hydroxyapatite powder slurry, and use a pen to dip the silver-containing hydroxyapatite powder The slurry is used to seal the surface of the biscuit body in contact with the skin and the part protruding from the skin, and obtain the sealed biscuit body after drying;9).烧成：9). Firing:将干燥好的素烧坯体放入硅碳棒炉中进行烧成，升温速度5～10℃/min，升温至1220℃保温2小时，然后断电随炉冷却，得到渗透型羟基磷灰石多孔陶瓷，即多孔陶瓷埋置体。Put the dried biscuit body into a silicon carbide rod furnace for firing. The heating rate is 5-10°C/min, and the temperature is raised to 1220°C for 2 hours, and then the power is turned off and the furnace is cooled to obtain infiltrated hydroxyapatite. Porous ceramics, that is, porous ceramic embedded bodies.2.根据权利要求1所述的用于局部给药的多孔生物陶瓷经皮植入装置，其特征在于：橡胶安全帽上设有输液管(6)，橡胶安全帽与输液管(6)连成一体，输液管(6)与储药凹槽相连通。2. The porous bioceramic percutaneous implantation device for local administration according to claim 1, characterized in that: the rubber safety cap is provided with an infusion tube (6), and the rubber safety cap is connected with the infusion tube (6). Into one body, the infusion tube (6) communicates with the drug storage groove.3.根据权利要求1所述的用于局部给药的多孔生物陶瓷经皮植入装置，其特征在于：多孔陶瓷埋置体(2)下端部的外径大于多孔陶瓷埋置体(2)上端部的外径。3. The porous bioceramic percutaneous implant device for local administration according to claim 1, characterized in that: the outer diameter of the lower end of the porous ceramic embedding body (2) is greater than that of the porous ceramic embedding body (2) The outer diameter of the upper end.4.根据权利要求1所述的用于局部给药的多孔生物陶瓷经皮植入装置，其特征在于：多孔陶瓷埋置体(2)的下部为回转体，多孔陶瓷埋置体(2)的上部为回转体。4. The porous bioceramic percutaneous implant device for local administration according to claim 1, characterized in that: the bottom of the porous ceramic embedding body (2) is a rotary body, and the porous ceramic embedding body (2) The upper part is a body of revolution.

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