CN106265080B

CN106265080B - 3D printing method of medicine and 3D printing medicine shell

Info

Publication number: CN106265080B
Application number: CN201610808924.3A
Authority: CN
Inventors: 徐效文; 赵景洲
Original assignee: Central South University
Current assignee: Central South University
Priority date: 2016-09-08
Filing date: 2016-09-08
Publication date: 2019-12-24
Anticipated expiration: 2036-09-08
Also published as: CN106265080A

Abstract

The invention discloses a method for 3D printing of a medicine and a 3D printing medicine shell, wherein the medicine shell comprises a regular tetrahedron cavity; the regular tetrahedron cavity is inscribed in the sphere; the sphere center of the sphere is coincided with the geometric center of the regular tetrahedron cavity. The method is simple and reliable, and the prepared pills are suitable for controlled release medicines and occasions with higher requirements on the stability of the medicines.

Description

3D printing method of medicine and 3D printing medicine shell

Technical Field

The invention relates to the field of controlled release medicines, in particular to a 3D medicine printing method and a 3D medicine printing shell.

Background

Controlled release drugs have been one of the key points in pharmacokinetic studies, and can greatly improve the utilization rate of the drugs. In modern pharmacy and clinical practice, the controlled release medicine has wide application prospect. Many scholars and manufacturers at home and abroad have a large amount of research achievements in the field. The 3D printing technology becomes a representative of advanced productivity more and more along with the popularization of open source hardware, the additive manufacturing mode capable of generating a complex structure and the controlled release medicine are used alternately, the release characteristic of the medicine is customized according to the requirements of patients, and the prospect is wide.

In the existing research results, foreign researchers have printed controlled release drugs with various characteristics using FDM type printers. The medicine with a release curve as a convex function (called concove abroad and the definition is opposite to that of domestic) can be used for impact treatment; the drug with a release curve of concave function (convex) can be used for patients with drug resistance; the drug whose release curve is a linear function can be used in long-term equivalent elimination situations. In some studies, multiple different compositions of drugs are printed into one tablet using a multi-component printer. There have also been some studies to pre-program the release of printed drugs by customizing the surface area to volume ratio of the digital model.

Many research results control the constant speed increase of the release curve of the drug, but there are many disadvantages in the method, such as excessive steps, the printed drug must resist high temperature, the advantages of the 3D printing technology for complex structures are not fully exerted, and the like, and the 3D printing still has great potential for pharmaceutical technology and is not excavated. The U.S. Food and Drug Administration (FDA) has approved the marketing of 3D printed drugs. 3D printing of controlled release drugs is expected to play a greater role with advances in technology and the passage of time.

The release rate of conventional drugs is divided into zero order release and first order release (i.e., constant elimination and constant ratio elimination). But neither will be slow to fast at the time of release. Certain specific diseases and specific fields, such as hypertension, cannot be satisfied. Hypertension patients generally reach a peak value in six to ten hours in the morning, and blood concentration of the hypertension patients does not reach the maximum value in the peak time of blood pressure after taking common medicines in the morning. If the medicine prepared by the method is taken before sleep, the blood concentration can reach the highest level in the time period from six to ten points in the morning, and the blood pressure is effectively controlled. In addition, the drug can also play a great role in certain specific occasions, for example, patients with drug tolerance require that the dosage at the later moment is larger than that at the former moment, and if the drug is controlled to be eliminated in an equivalent manner at most by using a common mode, the release speed of the drug cannot be controlled to be slow to high.

Disclosure of Invention

The invention aims to solve the technical problem that the prior art is insufficient, and provides a method for 3D printing of a medicine and a 3D printing medicine shell.

In order to solve the technical problems, the technical scheme adopted by the invention is as follows: a method of 3D printing a medication, comprising the steps of:

1) constructing a regular tetrahedron, finding out the geometric center of the regular tetrahedron, and using the geometric center as a sphere to be circumscribed on the regular tetrahedron. Performing Boolean operation on the sphere and the regular tetrahedron to enable the sphere to form a regular tetrahedron cavity to obtain a shell model, and storing the shell model as a drug shell model in an STL format;

2) importing the digital model in the STL format into slicing software for calculation to generate a G code;

3) the G code is identified and printed by an FDM 3D printer, and in the printing process, a fused polyvinyl alcohol wire is fused by a nozzle of the FDM 3D printer and then stacked according to a G code path generated by the medicine shell model, and a shell is printed and generated;

4) mixing polyvinyl alcohol powder and medicine powder, mixing the mixed powder with water, wherein the weight ratio of all the powder to the water is 6:4 or 5:5, and fully stirring to obtain gel;

5) injecting the gel into the shell from a needle with the inner diameter of 0.5mm to 0.7mm at a constant speed;

6) drying the whole pill at 70-80 deg.C for 8-10 hr to obtain a hard-shelled pill with dry core.

In step 1), the change of the regular tetrahedron is 10 mm.

In the step 1), the radius of the sphere is 12.4 mm.

In step 2), the parameters of the slicing software are set as follows: the layer height is 0.15 mm; the diameter of the spray head is 0.3 mm; the hot bed temperature is 70 ℃; the temperature of the spray head is 180 ℃; the printing speed was 80 mm/s.

The polyvinyl alcohol wire was a 1.75mm diameter wire having a purity of 95%.

The invention also provides a 3D printing medicine shell for controlling the gradual quick release of the medicine, which comprises a regular tetrahedron; the regular tetrahedron is arranged in the sphere; the sphere center of the sphere is coincided with the geometric center of the regular tetrahedron.

Compared with the prior art, the invention has the beneficial effects that: the invention has simple operation and strong reliability. The hollow shell is formed in one step. The release speed of the medicine is controlled to be from slow to fast, the medicine model is compatible with various medicines which can not resist high temperature, can be scaled according to actual conditions to meet the requirements of different patients, and has strong customization. The resulting pills are suitable for use in controlled release pharmaceutical applications and in applications sensitive to drug resistance.

Drawings

FIG. 1 is a schematic diagram of modeling Boolean operations.

Detailed Description

The 3D printing medicine shell can control the medicine to have the characteristic that the concentration increases from slow to fast along with the time, and the structure of the medicine shell is a ball internally connected with a regular tetrahedron cavity; the printing material is polyvinyl alcohol wire; the application occasions are occasions of antihypertensive drugs and drug-resistant treatment; the concentration of the active ingredients of the medicine is from slow to fast when the active ingredients are released; the manufacturing method is printing by using an FDM type 3D printer. Can solve the problem that the drug release can not be from slow to fast.

First a digital modeling of the housing is performed. A regular tetrahedron with a side length of 10mm is established by using CAD computer aided drawing software. The geometric center of the regular tetrahedron is found. The external sphere of the regular tetrahedron is made by taking the geometric center as the sphere center, and the radius of the sphere is about 12.4 mm. And performing Boolean operation on the sphere and the regular tetrahedron, and hollowing the sphere into a shell internally connected with the cavity of the regular tetrahedron (shown in the figure I). The model is saved as a digital model in STL format.

And importing the model in the STL format into slicing software for calculation, and generating a G code (controlling a spray head path) for further importing into a printer. In the process, the parameter of the slicing software is that the layer height is 0.15 mm; the diameter of the spray head is 0.3 mm; the hot bed temperature is 70 ℃; the temperature of the spray head is 180 ℃; the printing speed is 80 mm/s; 1.75mm diameter 95% purity polyvinyl alcohol wire. And identifying and printing the G code derived in the last step to an FDM 3D printer. And in the printing process, the nozzle melts the melted polyvinyl alcohol wire and then stacks the polyvinyl alcohol wire according to the G code path, and the polyvinyl alcohol wire is formed to be hard after being cooled.

The printed shell was perforated at the thinnest point using a bench drill with a 0.7mm hole diameter.

Mixing the polyvinyl alcohol powder and the medicine powder, mixing the mixture with water, wherein the weight ratio of all the powder to the water is 6:4, the proportion of the medicine in the powder is determined according to specific requirements, and finally fully stirring to form the gel.

The gel was injected into the shell at a constant speed from a 0.5mm inner diameter needle using a 1ml syringe.

And drying the whole pill. Oven-drying at 70 deg.C for 8 hr.

Finally, the pill with hard shell and dry core is obtained, when in release, four corners of the regular tetrahedron are firstly leaked out, and the release speed of the active ingredients of the medicine is gradually increased.

When the composition is applied to occasions of reducing blood pressure, such as nifedipine, a patient can take the composition before sleeping at about 10 o ' clock in the evening, and the peak of hypertension is at the early morning (6 o ' clock to 12 o ' clock). At this time, the release speed of the active ingredients of the medicine is maximum, and the blood pressure is effectively reduced.

The present invention may also be suitably used in patients who develop drug resistance. Such patients require a greater amount of drug to be released at a later time than at a previous time. The present invention satisfies this feature. Meanwhile, the 3D printing technology can customize the sizes of the medicines for patients with different body sizes so as to meet different requirements.

Claims

1. A method of 3D printing a medication, comprising the steps of:

1) constructing a regular tetrahedron, finding out the geometric center of the regular tetrahedron, and using the geometric center as a sphere to be externally connected with the regular tetrahedron; performing Boolean operation on the sphere and the regular tetrahedron to enable the sphere to form a regular tetrahedron cavity to obtain a shell model, and storing the shell model as a drug shell model in an STL format;

2. The method for 3D printing of a medication according to claim 1, wherein in step 1) the sides of the regular tetrahedron are 10 mm.

3. The method for 3D printing of a medication according to claim 2, wherein in step 1) the sphere radius is 12.4 mm.

4. The method for 3D printing of drugs according to claim 1, wherein in step 2), the parameters of the slicing software are set as: the layer height is 0.15 mm; the diameter of the spray head is 0.3 mm; the hot bed temperature is 70 ℃; the temperature of the spray head is 180 ℃; the printing speed was 80 mm/s.

5. The method of 3D printing a medication according to claim 4, wherein the polyvinyl alcohol wire is a 95% pure 1.75mm diameter wire.

6. A3D printing medicine shell for controlling gradual and rapid medicine release is characterized by comprising a regular tetrahedron; the regular tetrahedron is arranged in the sphere; the sphere center of the sphere is coincided with the geometric center of the regular tetrahedron; the manufacturing process of the medicine shell comprises the following steps: