CN114159184B

CN114159184B - Indicator and dental instrument with controlled release preparation

Info

Publication number: CN114159184B
Application number: CN202111539328.7A
Authority: CN
Inventors: 马兆宁; 黄雷
Original assignee: Shanghai Angel Align Medical Instrument Co ltd
Current assignee: Shanghai Angel Align Medical Instrument Co ltd
Priority date: 2021-12-15
Filing date: 2021-12-15
Publication date: 2025-01-10
Anticipated expiration: 2041-12-15
Also published as: CN114159184A

Abstract

The invention discloses an indicator with a controlled release preparation and a dental instrument, the indicator includes an indicator layer having a controlled release formulation that reacts under the action of an agent in the oral cavity. The invention can control the reaction rate of the indication layer by means of the controlled release preparation, and can greatly improve the accuracy of the wearing time indicated by the indicator, thereby improving the indication effect of the indicator.

Description

Indicator with controlled release formulation and dental appliance

Technical Field

The invention relates to the technical field of tooth correction, in particular to an indicator with a controlled release preparation and a dental instrument.

Background

In the dental field, many treatments are performed by wearing dental instruments in the mouth, such as orofacial muscle training devices and shell-like appliances based on polymeric materials, which are increasingly popular for their aesthetic, convenience and cleaning benefits.

Adequate dental tool wear time is an important guarantee of treatment during treatment, however, patient compliance is a problem that plagues clinicians due to discomfort in wear correction and the ready-to-take nature of dental tools.

Thus, on the one hand, suitable means are needed to improve patient compliance, and on the other hand, suitable means are needed to indicate whether the dental appliance is worn for a sufficient time.

In the prior art, the indicator can be used in the oral cavity to indicate the wearing time, but the problem of poor indication effect exists.

Disclosure of Invention

The invention aims to provide an indicator with a controlled release preparation and a dental instrument, wherein the indicator can improve the indication effect.

To achieve one of the above objects, one embodiment of the present invention provides an indicator with a controlled release formulation for a dental appliance, the indicator comprising an indicator layer with a controlled release formulation that reacts under the action of an agent in the oral cavity.

As a further improvement of an embodiment of the present invention, the controlled release formulation is used to control the reaction rate of the indicator layer to remain constant.

As a further improvement of an embodiment of the present invention, the indication layer further comprises a functional agent, and the indication layer releases the functional agent under the action of an agent in the oral cavity.

As a further improvement of an embodiment of the invention, the functional agent is uniformly distributed in the indicator layer.

As a further improvement of an embodiment of the present invention, the functional formulation is a breath freshening formulation and/or a pharmaceutical formulation.

As a further improvement of an embodiment of the present invention, the indication layer displays a pattern under the action of an agent in the oral cavity.

As a further improvement of an embodiment of the present invention, the indicator layer exhibits a pattern by a change in volume, shape, color, pattern or morphology.

As a further improvement of an embodiment of the present invention, the controlled release preparation swells under the action of an agent in the oral cavity to control the display pattern of the indication layer.

As a further improvement of an embodiment of the invention, the indicator layer exhibits a pattern by volume increase.

As a further improvement of an embodiment of the present invention, the indication layer includes an edible pigment, and the indication layer exhibits a pattern by a color change.

As a further improvement of one embodiment of the present invention, the indication layer includes a first layer and a second layer stacked, the first layer has a first color, and the controlled release preparation swells under the action of an agent in the oral cavity to control the first color to gradually permeate into the second layer.

As a further improvement of an embodiment of the present invention, the indicator further comprises an encapsulation layer encapsulating the indication layer, the encapsulation layer having elasticity.

As a further improvement of an embodiment of the present invention, the encapsulation layer is a transparent layer.

As a further improvement of an embodiment of the present invention, the indicator layer further comprises a filler material and an adhesive material.

As a further improvement of an embodiment of the present invention, the indicator layer further includes at least one of a lubricant, a disintegrant, an edible essence, and an edible pigment.

As a further improvement of an embodiment of the present invention, the controlled release formulation is a matrix-type controlled release formulation, a membrane-type controlled release formulation or an osmotic pump controlled release formulation.

As a further improvement of an embodiment of the present invention, the indicating layer is a tablet, and the thickness of the indicating layer ranges from 0.01mm to 5mm.

As a further improvement of an embodiment of the present invention, the indicator further includes an encapsulation layer encapsulating the indication layer, the encapsulation layer having a through hole communicating with the indication layer and the oral cavity.

As a further improvement of an embodiment of the present invention, the indicator further comprises a flow control layer located between the indication layer and the oral cavity, the flow control layer being configured to control a rate of entry of an agent in the oral cavity into the indication layer.

As a further improvement of an embodiment of the present invention, the flow control layer is a transparent layer.

As a further improvement of an embodiment of the present invention, the indication layer reacts to generate a change area, and the indicator further includes a scale area for indicating position information of the change area.

To achieve one of the above objects, an embodiment of the present invention provides a dental instrument for wearing in the oral cavity, comprising an indicator according to any one of the above aspects.

As a further improvement of an embodiment of the present invention, the dental appliance includes a dental appliance body and an indicator disposed on the dental appliance body, the dental appliance body defining a cavity for receiving a tooth.

As a further improvement of an embodiment of the invention, the indicator is arranged on a lingual side of the dental instrument body and/or the indicator is arranged on a labial side of the dental instrument body.

As a further improvement of one embodiment of the present invention, the dental appliance is a shell orthodontic appliance or an orofacial muscle trainer.

Compared with the prior art, the method has the beneficial effects that the reaction rate of the indication layer can be controlled by means of the controlled release preparation, the accuracy of the wearing time indicated by the indicator can be greatly improved, and the indication effect of the indicator is further improved.

Drawings

FIG. 1 is a schematic view of a dental instrument according to one embodiment of the present invention;

FIG. 2 is a schematic view of an indicator according to an embodiment of the present invention;

FIG. 3 is a schematic illustration of an indicator layer formed by the cooperation of a semipermeable membrane and a tablet core according to an embodiment of the present invention;

FIG. 4 is a schematic view of an indicator with an encapsulation layer according to an embodiment of the present invention;

FIG. 5 is a schematic representation of the color and volume change of an indicator when a controlled release formulation of an embodiment of the present invention swells;

FIG. 6 is a schematic diagram of an indicator with an encapsulation layer and a flow control layer according to an embodiment of the present invention.

Detailed Description

The present invention will be described in detail below with reference to specific embodiments shown in the drawings. These embodiments are not intended to limit the invention and structural, methodological, or functional modifications of these embodiments that may be made by one of ordinary skill in the art are included within the scope of the invention.

Referring to fig. 1 and 2, a dental instrument 100 and an indicator 10 according to an embodiment of the present invention are shown, the indicator 10 being used in the dental instrument 100.

Here, the dental appliance 100 is used for being worn in the oral cavity, and the present embodiment is described taking the dental appliance 100 as a shell-shaped orthodontic appliance as an example, and in other embodiments, the dental appliance 100 may be another dental appliance that needs to be worn in the oral cavity for a certain period of time, such as an orofacial muscle trainer, etc.

The dental appliance 100 includes a dental appliance body 101 and an indicator 10 provided on the dental appliance body 101, the dental appliance body 101 forms a cavity S for receiving a tooth, and the dental appliance body 101 is generally made of a transparent material.

The cavity S in which the dental appliance 100 receives the teeth has a geometry that repositions the patient ' S teeth from the first configuration to the second configuration, e.g., the geometry of the cavity S of the dental appliance 100 may be determined based on the second configuration of the patient ' S teeth, or the geometry of the cavity S of the dental appliance 100 may substantially conform to the second configuration of the patient ' S teeth.

In this embodiment, the indicator 10 may be a separately manufactured product for subsequent use in the dental appliance 100.

The indicator 10 is provided on the lingual side of the dental instrument body 101 and/or the indicator 10 is provided on the labial side of the dental instrument body 101.

The number and positions of the indicators 10 are not limited, and may be determined according to the actual situation, and it is only necessary to ensure that the indicators 10 can contact the oral environment.

The indicator 10 may be secured to the dental instrument body 101 by spraying, fixing, or bonding, for example, the indicator 10 may be secured to the dental instrument body 101 with a glue.

The shape of the indicator 10 may be a cylinder, cone, rotator, cross-section, or any other regular or irregular shape, as the case may be.

In this embodiment, the indicator 10 includes an indicator layer 11 having a controlled release formulation, the indicator layer 11 reacting under the action of an agent in the oral cavity.

Here, the substance in the oral cavity is a factor that can control the reaction of the indicator layer 11, and the substance is saliva in the oral cavity, for example, specifically, temperature, PH, moisture, enzyme, protein, or the like in the saliva environment.

"Indicating layer 11 with a controlled release formulation" means that the controlled release formulation is part of the indicating layer 11, and the controlled release formulation controls the reaction rate of the indicating layer 11 by generating physical and chemical reactions under the action of an agent in the oral cavity.

In the prior art, the worn duration of the indicator 10 is generally determined based on the current state after the reaction of the indicating layer 11, and when the reaction rate of the indicating layer 11 is not controlled, the actual worn duration required for the indicating layer 11 to reach a certain state is inaccurate, that is, the actual reaction rate of the indicating layer 11 is too fast or too slow compared with the expected reaction rate, which results in that the actual worn duration is not matched with the expected worn duration, and thus the worn duration indicated by the indicator 10 is inaccurate, and the indication effect of the indicator 10 is poor.

The reaction rate of the indication layer 11 can be controlled by means of the controlled release preparation in the embodiment, so that the accuracy of the wearing time indicated by the indicator 10 can be greatly improved, and the indication effect of the indicator 10 is further improved.

In the present embodiment, the indication layer 11 exhibits a pattern by an action in the oral cavity.

That is, "the indication layer 11 reacts under the action of the substance in the oral cavity" means that the indication layer 11 displays a pattern under the action of the substance in the oral cavity, and the controlled release preparation can be used to control the rate at which the indication layer 11 displays a pattern.

The indicator layer 11 exhibits a pattern by a change in volume, shape, color, pattern or morphology.

That is, by "indicating layer 11 exhibits a pattern" is meant that the state of the indicating layer 11 changes, e.g., the volume, shape, color, pattern, or morphology of the indicating layer 11 changes, which may be visually observed, and different degrees of change may be used to characterize different durations of wear of the indicator 10, and a controlled release formulation may be used to control the rate of change of the state of the indicating layer 11, e.g., a controlled release formulation is used to control the rate of change of the volume of the indicating layer 11.

The state change of the indication layer 11 includes that the indication layer 11 gradually dissolves or swells to change the volume of the indication layer 11, or that the shape, color, pattern, etc. of the indication layer 11 changes with the increase of the wearing time period, or that the indication layer 11 changes from a solid state to a liquid state with the increase of the wearing time period, for example.

The state change of the indication layer 11 is not limited to the above description, and the determination of the state change of the indication layer 11 may be either a qualitative determination or a quantitative determination.

The quantitative judgment is provided with a quantitative mark matched with the indication layer 11, and the compliance is judged by the indication of the quantitative mark, so that the result is more accurate.

For example, the indication layer 11 reacts to generate a change area, and the indicator 10 further includes a scale area, which can be used as a quantization mark to indicate position information of the change area, so that the indication effect of the indicator 10 is better.

Alternatively, the indication layer 11 may display a pattern through a change of the indication layer 11, that is, the indication layer 11 has an indication function, or the indicator 10 further includes other structures having an indication function, and the change degree of the indication layer 11 is represented by the other structures having the indication function, so as to further represent the wearing duration of the indicator 10, which will be described later specifically.

In addition, the multiple states of the indication layer 11 may change at the same time, for example, the volume and color of the indication layer 11 change at the same time as the wearing time period increases.

In this embodiment, the indication layer 11 further includes a functional agent, and the indication layer 11 releases the functional agent by an action substance in the oral cavity.

The functional preparation is breath freshening preparation and/or pharmaceutical preparation.

In this embodiment, the functional agent is uniformly distributed in the indication layer 11, and thus, the controlled release agent can effectively control the release rate of the functional agent.

Specifically, the controlled release formulation of the present embodiment is used to control the reaction rate at which the indicator layer 11 is kept constant, i.e., the various portions of the indicator layer 11 can be released constantly.

Here, "kept constant" means that the reaction rate of the indicator layer 11 is kept substantially within a range where fluctuation is small, and does not mean that the reaction rate is always kept at an absolute value.

In addition, taking the case that the volume of the indication layer 11 becomes smaller under the action of the action object in the oral cavity as an example, the controlled release preparation can make the volume of the indication layer 11 become smaller at a constant speed, and the functional preparation is released into the oral cavity at a constant speed, so that the indication effect and the specific function of the wearing duration of the indicator 10 can be improved at the same time.

That is, the controlled release formulation of the present embodiment can achieve zero-order release of the indicating layer 11, which means that the release rate of each portion in the indicating layer 11 does not change with time and concentration, i.e., the release rate is kept constant during the release period of the indicating layer 11, the volume of the indicating layer 11 becomes small and the process of releasing the functional formulation is not affected by other factors.

In the following, several examples of functional formulations are specifically described.

In a first specific example, the functional formulation is a breath freshening formulation.

In the field of dentistry, many treatments are needed to be completed by wearing a shell-shaped orthodontic appliance (namely an invisible appliance), wherein, due to the fact that a patient wears the shell-shaped orthodontic appliance for a long time, saliva secretion in the mouth is abnormal, microecology changes, and the problem of breath often occurs, in daily life, the oral appliance has a fresh breath, so that personal confidence can be improved, personal charm can be increased, social quality can be improved, in addition, in the wearing process of the shell-shaped orthodontic appliance, a doctor usually does not recommend to use foods such as chewing gum or fresh breath slices, and therefore, social interaction and psychological health of people can be influenced.

The indication layer 11 of the indicator 10 of the present embodiment includes a breath freshening preparation which not only itself releases a scent to mask the bad breath in the oral cavity, but also the scent is felt by the patient when the patient is engaged with the shell orthodontic appliance having the indicator 10, so that the shell orthodontic appliance having the breath freshening preparation can greatly enhance the product strength, and at the same time, increase the product interestingness, and further increase the patient compliance, particularly the compliance of KID product patients.

The indication layer 11 of the present embodiment releases the breath freshening preparation under the action of the agent in the oral cavity, that is, the indicator 10 has both the functions of breath freshening and compliance indication, and can achieve a better therapeutic effect.

The breath freshening preparation is at least one of plant extract component, medicinal material extract component, animal extract component, fungus extract component, etc. or artificial component, such as menthol in plant extract, artificial edible essence, etc.

In a second specific example, the functional formulation is a pharmaceutical formulation.

Here, the pharmaceutical formulation may be effective in treating or alleviating oral or other diseases, thereby addressing the physiological needs of the patient.

For example, the pharmaceutical preparation contains fluorine or related components and can play a role in preventing caries, or the pharmaceutical preparation contains tea polyphenol and can play a role in inhibiting bacteria, or the pharmaceutical preparation contains borneol and boron powder and can play a role in treating canker sore, or the pharmaceutical preparation contains common antibiotics (such as amoxicillin, gentamicin, clarithromycin, amoxicillin and the like) and can play a role in diminishing inflammation.

Of course, the pharmaceutical preparation is not limited to the above description, and a suitable pharmaceutical preparation can be selected according to actual needs, and at this time, the manufactured indicator 10 has the functions of pharmacological and compliance indication, so that a better therapeutic effect can be achieved.

In this embodiment, the controlled release preparation includes a matrix type controlled release preparation, a membrane type controlled release preparation or an osmotic pump controlled release preparation, and the release mechanism of the controlled release preparation mainly includes dissolution, diffusion, erosion, osmotic pressure, ion exchange, and the like.

In the following, several specific examples of the controlled release formulation are described in detail.

In the first specific example, the controlled release formulation is a matrix type controlled release formulation, and can be specifically classified into the following four cases.

In the first case, the controlled release preparation is a hydrophilic gel matrix tablet, and at this time, materials forming the hydrophilic gel matrix tablet may be classified into four types (1) natural gums such as sodium alginate, agar, tragacanth, xanthan gum, guar gum, and the like, (2) cellulose derivatives such as Methyl Cellulose (MC), hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (CMCNa), and the like, (3) cellulose polysaccharides such as chitin, galactose, mannan, and the like, (4) ethylene polymers and acrylic resins such as polyvinyl alcohol, polyethylene, and the like.

Here, the main material of the hydrophilic gel skeleton tablet is hydroxypropyl methylcellulose (HPMC) for illustration, and the common hydroxypropyl methylcellulose is K4M (4000 kpa/s) and K15M (15000 kpa/s), and the drug release mechanism is that the gel skeleton tablet is formed rapidly when meeting water, so as to achieve the purposes of controlling initial release, controlling water diffusion and drug release by firm viscous gel, and controlling the release principle to be combination of erosion, diffusion and dissolution.

In particular, hydroxypropyl methylcellulose serves both as a drug depot and as a controlled release drug in the tablet (i.e., indicator layer 11).

The controlled release preparation with hydroxypropyl methylcellulose has the release mechanism that when the tablet is used in oral cavity, the controlled release preparation can form gel fast to reach initial release, water soluble adhesive material is used to reach slow release effect, the adhesive material has to hydrate on the surface of the tablet to form initial gel protecting layer, and compared with other cellulose, the hydroxypropyl methylcellulose has fast hydration rate to ensure the fast formation of the initial gel protecting layer, and the firm initial gel protecting layer controls saliva diffusion and medicine release.

The extent to which the gel protective layer is eroded depends on the viscosity of the high molecular polymer, the viscosity increases, and the drug release slows down, because the gel protective layer has correspondingly become stronger and more viscous, i.e., forms a stronger barrier, slowing down the dissolution rate and tablet loss.

It can be seen that the drug release process of the controlled release preparation with hydroxypropyl methylcellulose is a complex process of interaction of water, polymer, framework material and drug, the drug release is affected by factors such as water penetration, polymer swelling, drug dissolution and diffusion, framework erosion and the like, the hydroxypropyl methylcellulose forms gel after meeting water, the release rate of the water-soluble drug depends on the diffusion rate of the drug through the gel layer, the release rate of the drug with low solubility in water is determined by the gradual erosion rate of the gel layer, no matter which drug release mechanism is adopted, the gel is completely dissolved at last, and the drug is completely released, so the bioavailability is high.

In the second case, the controlled release formulation is a waxy matrix tablet, where the waxy matrix tablet is formed from an insoluble but erodable waxy material, such as carnauba wax, stearyl alcohol, stearic acid, polyethylene glycol, hydrogenated castor oil, polyethylene glycol monostearate, triglycerides, etc., the mechanism of release of the waxy matrix tablet is controlled release by cell diffusion in combination with erosion, and a portion of the drug is encapsulated by a water impermeable wax to facilitate its release, and a surfactant is typically used in combination with stearyl alcohol or stearic acid.

In the third case, the controlled release preparation is an insoluble matrix tablet, at this time, the material forming the insoluble matrix tablet is polyethylene, polyvinyl chloride, methacrylic acid-methyl acrylate copolymer, ethylcellulose, etc., the drug release mechanism of the insoluble matrix tablet is that liquid penetrates the matrix to dissolve the drug, then diffuses out from the grooves of the matrix, and the drug release is in combination with dissolution, and responds to the channel diffusion to limit the speed step, the release accords with the Higuchi equation, and the bioavailability depends on the ratio of the drug to the controlled release polymer.

In the fourth case, the controlled release preparation is a controlled release microcapsule, and the controlled release microcapsule controls the diffusion speed of the medicine to the body fluid by selecting different encapsulating materials, controlling the thickness of the encapsulating materials and other methods, so as to achieve the purpose of slow release and delay effect, and the release mechanism comprises dissolution, diffusion, degradation, particle breaking and the like.

In a second specific example, the controlled release formulation is a membrane controlled release formulation.

Here, the membrane controlled release preparation refers to a controlled release preparation prepared by coating one or more layers of coating materials on the surfaces of tablets, particles and pellets, wherein the release mechanism of the membrane controlled release preparation is diffusion release, and the dynamic force is osmotic pressure or dissolution and diffusion behaviors of drug molecules in a polymer.

The membrane controlled release preparation is different from the framework controlled release preparation mainly in the controlled release mode, the framework controlled release preparation is formed into framework type materials (for example, a hydrophilic gel framework tablet can form framework materials only when meeting water), and the membrane controlled release preparation is formed into a preparation, a tablet or a pellet coated with a coating or a coating, and can be specifically divided into the following three cases.

In the first case, the membrane controlled release formulation is a microporous membrane controlled release formulation, and polymers insoluble in the oral cavity such as cellulose acetate, ethylene-vinyl acetate copolymer, polyacrylic resin, etc. are used as coating materials, and a small amount of a substance such as PEG, PVP, PVA, SDS, sugar, salt or a drug is added as a pore-forming agent to its coating liquid, and the controlled release principle is diffusion.

In the second case, the membrane controlled release preparation is a membrane controlled release tablet, the membrane controlled release tablet is prepared by granulating the drug and the auxiliary materials according to a conventional method, pressing the drug and the auxiliary materials into a tablet, and forming a coating with the diameter of about 3mm, wherein the controlled release principle is diffusion.

In the third case, the membrane controlled release preparation is a membrane controlled release pellet, and the membrane controlled release pellet consists of a pellet core and a coating coated outside the core, wherein the controlled release principle is diffusion.

In a third specific example, the controlled release formulation is an osmotic pump controlled release formulation.

Here, the osmotic pump controlled release preparation refers to a controlled release tablet taking osmotic pressure as a drug release energy source, and the drug release mechanism of the osmotic pump controlled release preparation is osmotic pressure.

Osmotic pump controlled release formulations are typically composed of a tablet core composed of a pharmaceutical formulation (e.g., a breath freshening formulation), an osmotically active substance, a propellant, and the like, and a semipermeable membrane.

Referring to fig. 3, the tablet core 202 is coated with the semipermeable membrane 201, and due to the osmotic pressure difference between the inside and the outside of the semipermeable membrane 201, water soluble particles and liquid medicine in the semipermeable membrane 201 permeate into the tablet core 202, and due to the volume limitation, the tension of the semipermeable membrane 201 causes the liquid medicine to release the liquid medicine out of the semipermeable membrane 201 through the medicine release holes 2011 on the semipermeable membrane 201, so long as the medicine in the semipermeable membrane 201 maintains a saturated solution state, the release rate is constant, and the medicine can be released at zero-order rate.

The semipermeable membrane 201 may be made of cellulose acetate, EC, etc., the osmotic active substance may be selected from lactose, fructose, glucose, mannitol, etc., the pushing agent may be selected from poly (hydroxy methyl acrylic acid) alkyl ester (molecular weight 3-500 ten thousand), PVP (molecular weight 1-36 ten thousand), etc., and the other additives include suspending agent, binding material, lubricant, and wetting agent.

Specifically, when the active substance in the oral cavity enters the tablet core 201 from the semipermeable membrane 201, the high polymer material polyethylene oxide added in the boosting layer absorbs water and expands to generate higher swelling pressure and osmotic pressure, so that the drug suspension in the drug-containing layer is pushed to release from the drug release hole 2011.

In the present embodiment, the indication layer 11 further includes a filler and an adhesive.

That is, the indication layer 11 mainly includes a breath freshening agent, a controlled release agent, a filling material and an adhesive material, and the indication layer 11 has a tablet structure, but not limited thereto.

Here, the main function of the filler material is to improve the material properties, and the main function of the adhesive material is to adhere the separated materials together by means of tackiness.

In the present embodiment, the indicator layer 11 further includes at least one of a lubricant, a disintegrant, an edible essence, and an edible pigment.

The lubricant is used for smoothly feeding materials, reducing viscosity and punching, reducing friction force and enabling the surface of the tablet to be smooth and attractive during tabletting.

The lubricant includes a glidant, an anti-sticking agent and a lubricant (narrow sense), and at least one of a fluid lubricant, a boundary lubricant, and a mixed lubricant may be selected according to types.

Specifically, the lubricant is at least one of magnesium stearate, calcium stearate, zinc stearate, microcrystalline cellulose, micro-powder silica gel, talcum powder, polyethylene glycol, glyceryl monostearate, hydrogenated vegetable oil, sodium stearyl fumarate, sodium lauryl sulfate or magnesium lauryl sulfate.

The disintegrating agent can select at least one of capillary action disintegrating agent, swelling action disintegrating agent, gas-generating action disintegrating agent, enzymolysis action disintegrating agent, etc. according to action mechanism, and the disintegrating agent has the function of auxiliary material capable of rapidly disintegrating the tablet into small molecules.

Optionally, an edible essence, an edible pigment, etc. may be added to the indication layer 11.

In this embodiment, the process flow of the tablet-shaped indication layer 11 mainly includes three parts of raw material treatment, granulation and tabletting, and specifically includes:

And (3) raw material treatment, namely selecting proper filling materials according to the requirements of a formula, grinding and sieving to screen particles.

Granulation most of tablets are required to be granulated and then tableted, which is determined by the properties of materials, and the granulation is mainly to increase the fluidity and compressibility of the tablets, and the granulation method mainly comprises an extrusion granulation method, a wet mixing granulation method, a spray rotation granulation method, a fluidization spray granulation method and a spray drying granulation method.

Tabletting methods include direct compression or tabletting, dry granulation and wet granulation, in which the raw material-treated powder materials are blended together and directly compressed without intermediate processing, such as a granulation process.

Wherein the dry granulation process comprises mixing the components, compressing the mixture into a tablet preform, dry sieving or grinding into dry coarse granules, lubricating and compacting the lubricated granules, and the wet granulation process comprises mixing part or all of the dosage form, then adding a solution of binding material to the powder of the blend to effect granulation, and then sieving and drying the wet mass, for example by disc drying, drying using a fluid bed dryer, spray dryer, high frequency dryer, microwave, vacuum or infrared dryer.

In the present embodiment, the thickness of the indicator layer 11 is in the range of 0.01mm to 5mm, but is not limited thereto.

In one embodiment, the breath freshening formulation is menthol (0.01-0.5%), the filler material is mannitol (10-50%), the binder material is microcrystalline cellulose (45-85%), the controlled release formulation is hydroxypropyl methylcellulose (1-20%), and the lubricant is magnesium stearate (0.5-3%), which is gradually soluble in saliva.

In this particular embodiment, the co-processed composition is a particulate composition having an average particle size of about 30 to 800 microns, preferably 50 to 90 microns, using 70 ℃ water, adding an acidic microcrystalline cellulose wet cake to a mannitol solution to form a microcrystalline cellulose and mannitol mixture, subjecting the mixture to ammonia neutralization and spray drying, and thereafter lubricating with magnesium stearate, and then compressing into a tablet, which is a wafer, having a thickness of 0.5mm, and the resulting tablet (i.e., indicator layer 11) is directly adhered to the outer surface of dental appliance body 101 with a food gum, where the tablet has the effect of both compliance indication and controlled release breath freshening formulation.

In yet another embodiment, the breath freshening formulation comprises green tea powder flavor (0.01-0.5%), the filling material is isomalt (45-50%), the binding material is microcrystalline cellulose (45-50%), the controlled release formulation comprises hydroxypropyl methylcellulose (5-20%), and the lubricant comprises magnesium stearate (0.5-3%).

In this particular example, the co-processed composition was a particulate composition having an average particle size of about 20-200 microns and was directly compressed using a rotary tablet press for mixing, the tablets were round, had an average diameter of 2.9-3.1mm and an average thickness of 1.2-1.8mm, and the resulting tablets (i.e., the indicia containing layer 11) were adhered directly to the outer surface of the dental appliance body 101 with a food gum, the tablets having both compliance indicating and controlled release breath freshening formulations.

In this embodiment, the indication layer 11 may be directly disposed at the dental instrument body 101 as the indicator 10, and at this time, since the indication layer 11 is directly included in the oral environment, the addition of the controlled release agent can effectively control the reaction rate of the indication layer 11, so as to avoid the reaction rate of the indication layer 11 from being too fast, but not limited thereto.

Next, an indication process of the indication layer 11 will be described.

With reference to the foregoing description, some forms of controlled release formulations will swell under the action of an agent in the mouth, and the swelling process will control the display of the pattern on the indicia containing layer 11.

In a specific example, the controlled release preparation swells under the action of the agent in the oral cavity, so that the volume of the indication layer 11 becomes larger, and at this time, the indication layer 11 displays the pattern through volume increase, that is, the wearing duration of the indicator 10 can be represented according to the volume.

Here, in combination with fig. 4, the indicator 10 may further include an encapsulation layer 12 for encapsulating the indication layer 11, where the encapsulation layer 12 has elasticity, and on one hand, the encapsulation layer 11 is configured to prevent the indication layer 11 from being directly disintegrated into the oral cavity during swelling of the controlled release preparation, and on the other hand, the encapsulation layer 11 may be expanded in cooperation with the swelling process of the controlled release preparation, and the wearing period of the indicator 10 is characterized by the expansion process (i.e., the volume change process) of the encapsulation layer 11.

In another specific example, the indication layer 11 includes an edible pigment, and the indication layer 11 displays a pattern by a color change.

That is, when the controlled release preparation swells under the action of the agent in the oral cavity, since the indication layer 11 further includes the edible pigment, the color displayed by the edible pigment also changes during the swelling process, so that the wearing time of the indicator 10 is represented by the volume of the indication layer 11 (i.e. the volume of the encapsulation layer 12) and the color change.

Here, the encapsulation layer 12 is a transparent layer to facilitate viewing of the color change.

Specifically, referring to fig. 5, the indication layer 11 includes a first layer 111 and a second layer 112 stacked together, where the first layer 111 has a first color, and the controlled release preparation swells under the action of an agent in the oral cavity to control the first color to gradually permeate into the second layer 112.

Here, assuming that the first color is red and the second layer 112 is initially white, when the controlled release formulation in the indication layer 11 swells, the swelling process not only increases the volume of the indication layer 11, but also gradually permeates the red color into the white region of the second layer 112, and the current wearing period of the indicator 10 can be determined by observing the change in the volume of the encapsulation layer 12 and/or the area of the red region.

It should be noted that the encapsulation layer 12 may be made of a water-absorbing material, so that the active substance in the oral cavity may contact the indication layer 11 through the water-absorbing material.

Of course, in other embodiments, referring to fig. 6, the encapsulation layer 12 may have a through hole 121 for communicating the indication layer 11 with the oral cavity, and the substance in the oral cavity contacts the indication layer 11 through the through hole 121.

At this time, the encapsulation layer 12 may be made of a waterproof material, and the through hole 121 is smaller in size, so that the rinsing water is not easy to penetrate through the encapsulation layer 12 and enter the indicator 10 during the rinsing process of the dental instrument 100, and thus factors such as rinsing the dental instrument 100 can be prevented from affecting the accuracy of the indication of the indicator 10.

In this embodiment, the encapsulation layer 12 may be a porous polymer film, for example, made of polyurethane, silica gel, polyacrylic acid, or other polymers, and the amount of the active material to be transmitted can be adjusted by controlling the number and size of the through holes 121 of the encapsulation layer 12 (i.e., controlling the porosity of the encapsulation layer 12), so as to further precisely control the wearing time indicated by the indication layer 11.

In this embodiment, the indicator 10 further comprises a flow control layer 13 between the indication layer 11 and the oral cavity, the flow control layer 13 being configured to control the rate at which an agent in the oral cavity enters the indication layer 11.

At this time, the amount of the reactant reaching the indicating layer 11 can be controlled by the combined action of the through hole 121 of the encapsulation layer 12 and the flow control layer 13.

Wherein, the flow control layer 13 is a transparent layer, which can facilitate the observation of the state change of the indication layer 11.

It should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is for clarity only, and that the skilled artisan should recognize that the embodiments may be combined as appropriate to form other embodiments that will be understood by those skilled in the art.

The above list of detailed descriptions is only specific to practical embodiments of the present invention, and they are not intended to limit the scope of the present invention, and all equivalent embodiments or modifications that do not depart from the spirit of the present invention should be included in the scope of the present invention.

Claims

1. An indicator with a controlled release preparation, for use in dental instruments, characterized in that the indicator comprises an indicator layer with a controlled release preparation, the indicator layer reacts under the action of an agent in the oral cavity; the controlled release preparation is used to control the indicator layer to maintain a constant reaction rate, the controlled release preparation swells under the action of an agent in the oral cavity to control the indicator layer to display a pattern, the indicator layer displays the pattern by increasing its volume, the indicator layer comprises an edible pigment, the indicator layer displays the pattern by changing its color, the indicator layer comprises a first layer and a second layer stacked together, the first layer has a first color, the controlled release preparation swells under the action of an agent in the oral cavity to control the first color to gradually penetrate into the second layer, the indicator further comprises an encapsulation layer encapsulating the indicator layer, the encapsulation layer having elasticity.

2 . The indicator according to claim 1 , wherein the indicator layer further comprises a functional agent, and the indicator layer releases the functional agent under the action of an agent in the oral cavity.

3 . The indicator according to claim 2 , wherein the functional agent is evenly distributed in the indicator layer.

4 . The indicator according to claim 2 , wherein the functional agent is a breath freshening agent and/or a pharmaceutical agent.

5 . The indicator according to claim 1 , wherein the indicator layer displays a pattern under the action of an agent in the oral cavity.

The indicator according to claim 1 , wherein the encapsulation layer is a transparent layer.

7 . The indicator according to claim 1 , wherein the indicator layer further comprises a filling material and an adhesive material.

8 . The indicator according to claim 1 , wherein the indicator layer further comprises at least one of a lubricant, a disintegrant and an edible flavor.

9 . The indicator according to claim 1 , wherein the controlled-release preparation is a skeleton-type controlled-release preparation, a membrane-controlled-release preparation or an osmotic pump-controlled-release preparation.

10 . The indicator according to claim 1 , wherein the indicator layer is a tablet, and the thickness of the indicator layer is in the range of 0.01 mm to 5 mm.

11 . The indicator according to claim 1 , further comprising a packaging layer encapsulating the indicator layer, wherein the packaging layer has a through hole connecting the indicator layer and the oral cavity.

12 . The indicator according to claim 11 , characterized in that the indicator further comprises a flow control layer located between the indicator layer and the oral cavity, wherein the flow control layer is used to control the rate at which the agent in the oral cavity enters the indicator layer.

13. The indicator according to claim 12, characterized in that the flow control layer is a transparent layer.

14 . The indicator according to claim 1 , wherein the indicator layer reacts to generate a change area, and the indicator further comprises a scale area, wherein the scale area is used to indicate position information of the change area.

15. A dental device for wearing in an oral cavity, characterized in that it comprises the indicator according to any one of claims 1 to 14.

16 . The dental instrument according to claim 15 , wherein the dental instrument comprises a dental instrument body and an indicator disposed on the dental instrument body, and the dental instrument body forms a cavity for accommodating teeth.

17. The dental instrument according to claim 16, characterized in that the indicator is arranged on a side of the dental instrument body close to the tongue side, and/or the indicator is arranged on a side of the dental instrument body close to the labial side.

18. The dental instrument according to claim 15, characterized in that the dental instrument is a shell-shaped orthodontic appliance or an orofacial muscle trainer.