TW201406407A - Formulation excluding chemical additives and method for manufacturing the same - Google Patents

Abstract

A formulation structure is provided. The formulation includes a main body having holes and a thin film layer having pores and disposed on the surface of the main body. The thin film layer is more compact than the main body and integrally connected to the main body. A method for manufacturing the formulation is also provided.

Description

Formula containing no chemical additive and method of producing the same

The present invention relates to a formulation containing no chemical additives and a method of producing the same.

In the past, the tablet in the preparation has been further prepared by a dry granulation method, a wet granulation method or a direct method. In the above dry granulation method, the active ingredient and the chemical additive are subjected to a tableting process to prepare a tablet, and then the tablet is pulverized to form granules, and finally the granules are tableted to form a tablet. In the above wet granulation method, the active ingredient, the chemical additive and the solvent are first mixed, and then subjected to a drying process, followed by tableting to form a tablet. The above direct method is to directly inject the active ingredient with a chemical additive or the like. From this, it is understood that chemical additives must be added to the conventional production methods. If there is no chemical additive in the formulation, problems may occur in the process flow or mass production speed, or the stability or disintegration of the manufactured preparation may be poor. Chemical additives can provide certain functions, such as adjusting viscosity, improving lubricity to assist in process mass production, or improving formulation stability and adjusting disintegration.

For example, adhesives, diluents, glidants, lubricants, emulsifiers, or preservatives can help with actual mass production, improve prescription yield, or improve stability. Flavoring agents, flavors or pigments improve flavor and appearance. Disintegration agents can be used to adjust the rate of collapse of the drug. However, if the above-mentioned preparation containing chemical additives is used for a long time, it may cause adverse effects on the human body.

Therefore, there is a need for a formulation structure having good stability and a method of manufacturing the same, and avoiding the use of chemical addition in the preparation itself and its manufacturing process. Additives.

Accordingly, one aspect of the present invention is to provide a formulation comprising a body having a plurality of holes, and a film layer on the surface of the body and integrally connecting the body. The film layer has a plurality of pores, and the film layer is denser than the body. The film layer has the ability to support and stabilize the main structure, which can be naturally generated in the process or added after secondary processing.

In accordance with an embodiment of the present invention, a formulation includes a body having a plurality of holes, and a film layer on the surface of the body and integrally joining the body. The film layer has a plurality of pores, and the size of the pores is not larger than the size of the pores of the body.

According to another embodiment of the invention, a formulation comprises a body having a plurality of holes, and a film layer on the surface of the body and integrally connecting the body. The film layer has a plurality of pores, and the distribution density of the pores is not greater than the distribution density of the pores of the body.

Another aspect of the present invention is to provide a method of making a formulation comprising the following steps in sequence. Provide molds. The fluid is filled in a mold that does not contain chemical additives and contains the active ingredient and water. This fluid is lyophilized to form a solid which condenses into ice. The ice in the sublimation solid is allowed to form water vapor to leave to form a formulation. The formulation comprises a body having a plurality of holes, and a film layer on the surface of the body and integrally connecting the body. The film layer has a plurality of pores, and the size of the pores is not larger than the size of the pores of the body.

The above embodiments of the present invention have the following advantages:

(1) The preparation of the above embodiment of the present invention may contain no chemical additives to reduce the psychological and actual health effects on the user.

(2) In the preparation of the above embodiment of the present invention, the film layer is denser and more integrally connected to the main body than the main body, and therefore the film layer has a function of protecting the main body. In addition, the film layer can also isolate the body from the outside air, moisture or light, reduce the chance or rate of reaction between the body and the outside, so that the formulation has good chemical and biological stability.

(3) The preparation of the above embodiment of the present invention has a porous structure and thus has good disintegration properties.

The Summary of the Invention is intended to provide a simplified summary of the present disclosure in order to provide a basic understanding of the disclosure. This Summary is not an extensive overview of the disclosure, and is not intended to be an The basic spirit of the present invention, as well as the technical means and implementations of the present invention, can be readily understood by those of ordinary skill in the art.

The embodiments of the present invention are disclosed in the following drawings, and the details of However, it should be understood that these practical details are not intended to limit the invention. That is, in some embodiments of the invention, these practical details are not necessary. In addition, some of the conventional structures and elements are shown in the drawings in a simplified schematic manner in order to simplify the drawings.

Formulation structure

Please refer to FIG. 1 , which is a schematic cross-sectional view showing a preparation according to an embodiment of the present invention. Formulation 100 includes a body 110 and a film layer 120. The body 110 includes a plurality of holes 112, microparticles 114, fine powder 116, and a liquid 118. The film layer 120 has a plurality of fine holes 122 therein. And the film layer 120 is denser than the body 110.

The above structure can be used to prepare the preparation 100 using a freeze vacuum dryer, a mold and a special packaging material in combination with a freeze vacuum drying method and a molding method. After the end of the freeze vacuum drying process, the formulation 100 can be further processed to aid in shaping to enhance the appearance of the formulation 100. The above secondary processing means that the slight pressing can be performed 1-2 times. Therefore, the present preparation 100 can have a good molding effect without adding a chemical additive during the manufacturing process.

The shape of the body 110 is porous. The body 110 may include microparticles 114, fine powder 116, and liquid 118 in addition to a plurality of holes 112. The components of the body 110 may be free of chemical additives, i.e., completely active ingredients, which may reduce the health effects on the user.

The holes 112 may contain air, fine particles 114, fine powder 116 or liquid 118. Since the body 110 has a plurality of holes 112, it can help dissolve and disintegrate the formulation 100. The holes 112 may have a diameter of from 1 to 200 microns. The above-mentioned holes 112 may occupy 3-10% by volume of the main body 110.

The microparticles 114 and the fine powder 116 may be embedded in the body 110 or in the holes 112. The fine particles 114 may have a particle diameter of 100 to 800 μm, and the fine powder 116 may have a particle diameter of 0.1 to 99 μm. Microsome 114 and fine powder 116 may be free of chemical additives and excipients, ie, completely active ingredients. The difference between the fine particles 114 and the fine powder 116 is that the fine particles are processed into a spheroidal or cylindrical-like body by a plurality of complex processes, and the fine powder is a powder obtained by extracting and drying a single active component, which can be obtained by a simple process. The fine powder may be a spheroid, other fixed form or an irregular appearance.

Liquid 118 may still be present after vacuum freeze drying, which may be located in the bore 112. The composition of liquid 118 can be the active ingredient.

The film layer 120 is located on the surface of the main body 110, has a plurality of fine holes 122, and is integrally connected to the main body 110. The film layer 120 may be free of chemical additives and excipients, ie, completely active ingredients. The above "integral connection" means that when the preparation 100 is microscopically, it can be found that the structures of the film layer 120 and the main body 110 are continuously connected without a clear interface. The above structure can be produced by using a vacuum vacuum drying method in combination with a mold. Since the thin film layer 120 and the main body 110 have the fine holes 122 and the holes 112, respectively, they have good disintegration properties.

The difference in structure between the film layer 120 and the body 110 is that the density of the film layer 120 is significantly higher than that of the body 110. The difference in density can be obtained from the size and distribution density of the holes 112 and the pores 122 and the volume percentage of the body 110 and the film layer 120, respectively, of the holes 112 and the holes 122. Therefore, the size of the pores 122 is not larger than the size of the holes 112. Alternatively, the distribution density of the pores 122 is not greater than the distribution density of the pores 112. Still alternatively, the volume percentage of the pores 122 in the film layer 120 is not greater than the volume percentage of the holes 112 in the body 110. Since the film layer 120 is relatively dense and integrally connected to the body 110, the body 110 can be protected. Moreover, the film layer 120 can also isolate the body 110 from contact with the outside air, moisture or light, and reduce the chance or rate of reaction of the body 110 with the outside, so that the formulation 100 has good chemistry and biology. Stability. Therefore, the film layer has the ability to support and stabilize the physical structure of the body, which can be naturally generated in the process or generated after secondary processing.

The tablet composed of the main body 110 and the film layer 120 described above may have a thickness of 0.1 to 5 mm and may be circular, elliptical, square, rectangular or triangular in shape.

Composition of the preparation

As can be seen from the above, the composition of the preparation 100 composed of the main body 110 and the film layer 120 can be completely active ingredients and does not contain chemical additives, and can reduce the health effects on the user. The above chemical additives mean excipients, binders, disintegrating agents, diluents, glidants, lubricants, flavoring agents, emulsifiers, preservatives, perfumes or pigments.

The above active ingredient may be an active ingredient applied to foods or medicines. According to the activity, it can be divided into an active substance or an auxiliary active substance. The above active substance may be an organic acid, a fatty acid, a polypeptide or a protein, a probiotic, a fungus, an algae, an alkaloid, a flavonoid, a mineral or a chemical compound. The above auxiliary active substance may be a polysaccharide, a saccharide or a cellulose.

The above organic acid may be citric acid, malic acid, lactic acid, grain ferment, fruit ferment or other organic acid that can be applied to foods.

The above fatty acid may be an unsaturated fatty acid having a carbon chain of less than 50 carbon atoms. For example, Omega 3 fatty acids, Omega 6 fatty acids, Omega 9 fatty acids, lecithin or phosphoserine.

The above polypeptide or protein may be a polypeptide or protein having physiological regulation.

The probiotic may be Lactobacillus, Bifidobacterium, Bacillus, Bacillus subtilis, Streptococcus, Enterococcus or Yeast.

The fungus may be an edible or medicinal fungal hyphae, an edible or medicinal fungal fruiting body, an ascomycete fungus or a monosarcoma fungus. For example, the fungal material may be Antrodia camphorata, Cordyceps sinensis, Ganoderma lucidum, Cordyceps militaris, Yunzhi or Sclerotium.

The above algae may be edible or medicinal algae, including cyanobacteria, grape algae, green algae, red algae, nuclear algae, cryptophyta, dulgrass, purple red algae, and spirulina.

The above alkaloids may be extracts of plants, animals or fungi that can be applied to food additives. For example, piperine, fenugreek, theophylline and caffeine, resveratrol, serotonin, ergot and its derivatives, carnitine or choline.

The flavonoids may be flavonoids derived from fruits, vegetables, tea, wine, seeds or plant roots, or other flavonoids that may be applied to food additives. For example, the flavonoids may be rutin, hesperidin, quercetin, green tea polyphenols, red wine polyphenols or olive polyphenols.

The above minerals may be minerals that are edible or applied to food additives, including sodium salts, calcium salts, chromium salts, zinc salts, iron salts, magnesium salts, selenium salts.

The above cellulose may be derived from ginger, turmeric, pepper, garlic, scutellaria, bamboo leaves, mangosteen shell, orange peel, rambutan peel, yam, tea and other fibers.

Further, in the case where the content of the active ingredient is low or the physicochemical properties are not good, an appropriate amount of natural fibers or sugars may be added to enhance the structure of the preparation.

Preparation method of preparation

The preparation can be produced by a freeze vacuum drying method and a molding method. The process equipment includes a freeze vacuum dryer and a mold having a lower mold and a middle mold.

The steps for making the formulation are briefly described below. First, a release layer is placed over the lower mold, and the intermediate mold is placed over the release layer.

Then, a fluid (such as a semi-solid, a solution or a suspension) mainly composed of an active ingredient and water is filled into the mold, and another release layer is covered thereon. This step can be performed one or more times. If this step is performed multiple times, a multilayer ingot can be finally formed.

The form of the active ingredient in the fluid is not limited here, and may be, for example, a powder, a granule or a microparticle composed of other substances (excluding chemical additives).

In one embodiment, the active ingredient is first formed into microsomes, and the preparation of the preparation is carried out. The microsomes may have better physicochemical stability, palatability, or other pharmaceutical characteristics (eg, enteric, sustained release, etc.) than powders. Moreover, according to the process requirements, the density of the microsomes, the slow-release structure, the pH control of the dissolved outer shell, and the water-insoluble outer shell can be adjusted so that the processing does not disintegrate or dissolve.

Next, the water in the fluid is frozen to form ice using a freeze vacuum drying apparatus under appropriate low temperature conditions. Then, a low-pressure pumping and heating sublimation process is carried out to sublimate the solid (ice) into a gas (water vapor), leaving a preparation composed of the active ingredient.

In one embodiment, the formulation can be compressed one or more times to aid in the formulation of the formulation and to enhance its appearance. Therefore, in the preparation of the preparation The process can be carried out without adding chemical additives (such as excipients).

In one embodiment, air is introduced into the fluid with a microprobe to form small bubbles prior to the lyophilization fluid step. The fluid will form more pores or pores after lyophilization, thereby improving the disintegration characteristics of the preparation.

In one embodiment, the liquid is pumped into the fluid with a microprobe prior to the step of lyophilizing the fluid. This liquid does not leave after the freeze-drying step and is sealed in the body. The liquid is water-insoluble at ordinary temperatures, such as oils or lipids.

In one embodiment, the fluid contains a fine powder in a state of a suspension. After the freeze-drying step, the fine powder is sealed in the main body.

The aforementioned release layer is wrapped outside the tablet, and may be, for example, a sugar coating, a fat (solid at normal temperature), or an edible wax. After heating, the above materials can be filled into a mold to form a solid release layer. The release layer enhances the structural strength of the formulation as well as the environmental stability (such as the effect of moisture, oxygen or light on the formulation) without the use of antioxidants, preservatives or flavoring agents in the formulation of the formulation.

In several embodiments, the multi-layer ingot comprises one to more than one spacer layer, the spacer layer being the interval between the active and active components, the composition may be injected by the secondary fluid, the naturally formed interface, or the two fluid injections respectively. Ingredients for additional injection; the purpose of the spacer layer is to improve the properties of the formulation, including isolating reactive components that are easily reactive with each other, such as oxidizing agents and reducing agents, foaming components such as sodium bicarbonate and citric acid to enhance stability.

In several embodiments, the multilayer ingot may also be formed by injecting different fluids in divided portions. Partial injection to form different multi-layer ingots to improve the properties of the formulation, including isolating the active ingredients that are easily reactive with each other, or lifting the tablets Strength and integrity of the preservation process. As shown in Fig. 2, a mold release layer 210a is first placed on the mold 20, and the fluid is filled, and a spacer layer 210b is further provided to fill the fluid. The aforementioned fluids may be the same or different fluids. The release layer 210a and the spacer layer 210b may be the same material or different materials. For example, the two fluids may be an oxidant and a reducing agent, respectively, or an acid and a base, separated from each other by a spacer layer 210b. After the freeze-drying step and the sublimation step are sequentially performed, the preparations 100a, 100b are formed, each of which includes a body 110, a hole 112, a film layer 120, and pores 122.

The preparation can increase the yield of a specific prescription for application in mass production. In terms of application, it can be used for activity improvement of sensitive substance preparations.

The preparation can be developed into different dosage forms, such as rapid disintegration, swallowing, chewing, slow dissolution of the mouth, and dissolution in beverages.

The preparation process can be combined with a modified liposome or a nanosphere material such as a microsphere to increase the degree of oral absorption and change the pharmacokinetic properties to improve the bioavailability.

The preparation can be applied to physiological and pharmacological uses. For example, it can be applied to modulate physiological changes or indications caused by physiological disorders. Such as immune system activity disorders, including allergies, allergic rhinitis, atopic dermatitis, asthma, etc.; metabolic syndrome, including obesity, hyperlipidemia, fatty liver, diabetes, etc.; gastrointestinal physiology disorders, including constipation, flatulence, diarrhea, etc. And dysregulation of the urinary tract, including urinary tract infections, vaginal infections, and genital infections.

Although the present invention has been disclosed in the above embodiments, it is not intended to limit the present invention, and the present invention can be modified and modified without departing from the spirit and scope of the present invention. Fan The scope defined in the patent application scope is subject to the definition of patent application.

20‧‧‧Mold

110‧‧‧ Subject

100, 100a, 100b‧‧‧ preparations

114‧‧‧microsomes

112‧‧‧ hole

118‧‧‧Liquid

116‧‧‧fine powder

122‧‧‧Pore

120‧‧‧film layer

210a‧‧‧ release layer

210b‧‧‧ spacer

The above and other objects, features, advantages and embodiments of the present invention will become more <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt;

2 is a schematic cross-sectional view showing a preparation according to another embodiment of the present invention.

100‧‧‧ preparation

110‧‧‧ Subject

112‧‧‧ hole

114‧‧‧microsomes

116‧‧‧fine powder

118‧‧‧Liquid

120‧‧‧film layer

122‧‧‧Pore

Claims (13)

A preparation comprising: a body, wherein the body has a plurality of holes; and a film layer on the surface of the body and integrally connecting the body, wherein the film layer has a plurality of pores, the pores having a size no larger than The size of the holes. The preparation of claim 1, wherein the body comprises at least one microsome having a particle size of from 100 to 800 microns. The preparation according to claim 1, wherein the main body comprises at least one fine powder, and the fine powder is a water-soluble component, a fat-soluble component, a vesicle, a microsphere or a combination thereof, and the fine powder has a particle diameter of 0.1. -99 microns. The preparation of claim 1, wherein the pores have a diameter of from 1 to 200 microns. The preparation of claim 1, wherein the body and the film layer constitute a tablet having a thickness of 0.1 to 5 mm. A preparation comprising: a body, wherein the body has a plurality of holes; and a film layer on the surface of the body and integrally connecting the body, wherein the film layer has a plurality of pores, and the distribution density of the pores is not Big The distribution density of the holes. A method of making a formulation, comprising the steps of: providing a mold; filling a fluid in the mold, wherein the fluid does not comprise a chemical additive, and comprises the active ingredient and water; and lyophilizing the fluid to form a solid, wherein The water condenses into ice; and sublimates the ice to form water vapor to form the preparation, the preparation comprising: a body having a plurality of holes; and a film layer on the surface of the body And integrally connecting the body, wherein the film layer has a plurality of pores, and the pores have a size no larger than the size of the holes. The method of claim 7, after the step of sublimating the ice, further comprises pressing the preparation. The method of claim 7, further comprising pumping a gas into the fluid prior to the step of lyophilizing the fluid. The method of claim 7, further comprising pumping a liquid into the fluid prior to the step of lyophilizing the fluid. The method of claim 10, wherein the liquid is a fat, a liposome or a combination thereof. The method of claim 7, further comprising disposing a release layer on the mold before the step of filling the fluid. The method of claim 12, wherein the step of disposing the release layer and the step of filling the fluid are performed a plurality of cycles.