CN114699516A - Serratipeptidase enteric-coated preparation as well as preparation method and application thereof - Google Patents
Serratipeptidase enteric-coated preparation as well as preparation method and application thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a serrapeptase enteric preparation as well as a preparation method and application thereof. The invention creatively adopts the eutectic composition with low melting point as a dispersion medium to disperse the serrapeptase, and the serrapeptase is cooled and dried into solid particles after being granulated by a wet method. The process does not relate to a heating process above normal temperature, does not relate to any chemical reaction, is superior to a direct mixing process, can ensure that the small-size raw material serrapeptase is uniformly dispersed, can avoid the damage of high temperature to the serrapeptase, and is beneficial to controlling the particle size, thereby ensuring the stability of the content of the product.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a stable serrapeptase enteric preparation as well as a preparation method and application thereof.
Background
Serratin peptidase is a silkworm pupa secretion, is used for dissolving silkworm cocoon so as to enable larva to break cocoon and come out, is a protein hydrolase, can decompose tissue exudate, denatured protein fiber clot and the like, enables pus, phlegm, blood clot and the like to be liquefied and diluted and discharged, and can be used for resisting swelling and diminishing inflammation in oral cavity, five sense organs, mammary tissue and the like, eliminating phlegm and relieving cough in respiratory system, eliminating inflammation and sclerosis of cardiovascular system, enhancing therapeutic action by matching antibiotics and the like.
However, in the united states, serrapeptase, which is an enzyme, has the conventional characteristics of the enzyme, is not resistant to high temperature and high humidity, is easily damaged by acid, and the like, so that the titer of an enzyme preparation is easily influenced. This requires that high temperatures be avoided during the preparation and storage of the enzyme preparation, while it is formulated as an enteric preparation to avoid destruction by gastric acid.
The prior art provides a Serratin peptidase calcium alginate immobilization technology, which comprises the steps of firstly preparing sodium alginate solution of Serratin peptidase, then dripping calcium chloride to carry out crosslinking reaction, and then needing long-time solidification. In the process, the enzyme needs to undergo chemical reaction in the solution and be crosslinked and solidified, the production period is long, and the solidified enzyme intermediate is a solution product and is not suitable for preparing enteric solid preparations. Another prior art provides a serrapeptase powder for external use by preparing a suspension of silicon dioxide, titanium dioxide and serrapeptase and drying to a powder for external use. The technology can not ensure the binding force of the dried serrapeptase and auxiliary materials and the subsequent mixing uniformity, so the technology is also not suitable for preparing enteric solid preparations.
The conventional production process for preparing the serrapeptase enteric-coated tablets adopts the direct mixing of serrapeptase and auxiliary materials, but the conventional direct mixing process usually has the problem of poor mixing uniformity due to small medicine specification and the proportion of less than 10 percent, and an enteric coating process is adopted in the later period, so that the high-temperature and high-humidity environment not only causes great loss of serrapeptase raw materials, but also is not favorable for ensuring the production process of an enzyme preparation and the stability of the content of a product.
Disclosure of Invention
In view of the above, the primary object of the present invention is to provide a low melting point eutectic composition capable of ensuring the uniform preparation of small-sized preparations and also ensuring the stability of the enzyme preparation during the preparation process, so that the enzyme preparation does not need to undergo long-term aqueous solution, chemical reaction or high-temperature and high-humidity environment.
Another object of the present invention is to provide an enteric preparation and a method for preparing the same, which can ensure the release of an enzyme preparation in a specific intestinal tract part and has stable production process and product content.
The purpose of the invention is realized by the following technical scheme:
in one aspect, the present invention provides a eutectic composition comprising the following components: menthol, polyethylene glycol, and cetyl esters wax; the mass ratio of the menthol to the polyethylene glycol to the cetyl alcohol ester wax is (1-4): (2-3): (1-4).
Preferably, the mass ratio of the menthol to the polyethylene glycol and the cetyl esters wax is 1:3:4, 4:3:1 or 3:2: 3.
The invention also provides application of the eutectic composition in preparation of a pharmaceutical preparation.
On the other hand, the invention provides a serrapeptase enteric-coated preparation which comprises the following raw materials in parts by mass:
10 parts of serrapeptase, 24-56 parts of the eutectic composition, 142-174 parts of a filler, 10-10.5 parts of a disintegrating agent and 1.5-2 parts of a lubricant.
Optionally, the mass of the eutectic composition accounts for 15-20% of the total mass of the raw materials of the serrapeptase enteric-coated preparation.
Further, the mass of the eutectic composition accounts for 18.2% of the total mass of the raw materials of the serrapeptase enteric-coated preparation.
Optionally, the raw material composition of the serrapeptase enteric-coated preparation comprises: 10 parts of serrapeptase, 40 parts of the eutectic composition, 158 parts of a filling agent, 10.5 parts of a disintegrating agent and 1.5 parts of a lubricating agent.
Optionally, the filler is one or more of microcrystalline cellulose, pregelatinized starch, sucrose, lactose, starch, sorbitol, mannitol.
Optionally, the disintegrant is one or more of croscarmellose sodium, sodium starch glycolate, crospovidone, and low substituted hydroxypropylcellulose.
Optionally, the lubricant is one or more of magnesium stearate, zinc stearate, stearic acid, glyceryl monostearate, glyceryl palmitostearate.
The invention also provides a method for preparing the Serratide peptidase enteric-coated preparation, which comprises the following steps:
s1, mixing the menthol, the polyethylene glycol and the cetyl alcohol ester wax according to the prescription amount, heating and ensuring that the temperature does not exceed 38 ℃, adding serrapeptase after stirring and melting, and stirring uniformly to obtain liquid medicine for later use;
s2, uniformly mixing the filling agent and the disintegrating agent according to the prescription amount, adding the liquid medicine prepared in the step S1, and preparing wet granules by adopting a wet granulation process;
s3, drying the wet granules prepared in the step S2, mixing the dried wet granules with a lubricant, and filling the mixture into enteric capsule shells.
Alternatively, in step S2, the speed of stirring and mixing the filler and the disintegrant in the wet granulator is 120rpm for 2 min.
Optionally, the liquid medicine prepared in the step S1 is added into the mixture of the filling agent and the disintegrating agent within 50-70S.
Alternatively, the stirring speed is controlled to be 150rpm, the shearing speed is controlled to be 1200rpm, and the granulating time is controlled to be 5min during wet granulation.
Optionally, in step S3, the wet granules are put into a fluidized bed and dried by a cold trap, wherein the air inlet temperature is controlled to be 0-10 ℃, the air volume is controlled to be 400-600 m3/S, and the drying time is 10 min.
Optionally, in step S3, the filling speed of the capsule is 1200-1600 granules/min.
The dry particles prepared by the method have the granularity of 40-120 meshes, and the proportion of the dry particles is 60-80%.
The invention also provides application of the serrapeptase enteric preparation or the serrapeptase enteric preparation prepared by the method in preparation of medicaments for treating swelling and thick sputum.
Compared with the prior art, the technical scheme of the invention has the following advantages:
1. the eutectic composition provided by the invention consists of menthol, polyethylene glycol and cetyl alcohol ester wax in a specific ratio, the melting point of the eutectic composition is lower than 40 ℃, the eutectic composition is used as a dispersion medium of pharmaceutically active molecules after being melted, the dispersion uniformity can be ensured, the damage of the pharmaceutically active molecules caused by high temperature can be avoided, and the eutectic composition has the accessibility of solidifying into particles, so that the eutectic composition is very suitable for temperature-sensitive medicaments.
2. The preparation method of the Serratidase enteric-coated preparation provided by the invention is different from the conventional preparation process of the Serratidase, creatively adopts the eutectic composition with low melting point as a dispersion medium to disperse the Serratidase, and the Serratidase enteric-coated preparation is subjected to wet granulation and then is subjected to cold drying to obtain solid particles. The process does not relate to a heating process above normal temperature, does not relate to any chemical reaction, is superior to a direct mixing process, can ensure that the small-size raw material serrapeptase is uniformly dispersed, can avoid the damage of high temperature to the serrapeptase, is favorable for being solidified into particles, controls the particle size, and further ensures the stability of the content of the product.
3. The preparation method of the serrapeptase enteric-coated preparation provided by the invention fully considers the fact that serrapeptase is unstable in a gastric acid environment, so that enteric-coated capsules are adopted for protection, and in order to ensure the stability of a filling process and the uniformity of product content, the preparation method adopts a mode of controlling the particle size of dry particles (the proportion of the particle size between 40 meshes and 120 meshes is 60-80%), improves the filling process, and can prepare a product with good stability.
In addition, the wet granulation process has the advantages of simple process steps, few working procedures and simple and convenient operation, and is beneficial to large-scale production.
Detailed Description
The following examples are provided to further understand the present invention, not to limit the scope of the present invention, but to provide the best mode, not to limit the content and the protection scope of the present invention, and any product similar or similar to the present invention, which is obtained by combining the present invention with other prior art features, falls within the protection scope of the present invention.
The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all conventional reagent products which can be obtained commercially.
The embodiment of the invention provides a serrapeptase enteric-coated preparation which comprises the following raw materials in parts by weight:
10 parts of serrapeptase, 24-56 parts of eutectic composition, 142-174 parts of filler, 10-10.5 parts of disintegrating agent and 1.5-2 parts of lubricant;
wherein the eutectic composition is prepared from (1-4) by mass: (2-3): (1-4), preferably 1:3:4, 4:3:1 or 3:2:3, menthol, polyethylene glycol and cetyl esters wax. The weight of the eutectic composition accounts for 15-20% of the total weight of the raw materials of the serrapeptase enteric-coated preparation, and the preferred weight is 18.2%.
Optionally, the filler is one or more of microcrystalline cellulose, pregelatinized starch, sucrose, lactose, starch, sorbitol, mannitol.
Optionally, the disintegrant is one or more of croscarmellose sodium, sodium starch glycolate, crospovidone, low substituted hydroxypropylcellulose.
Optionally, the lubricant is one or more of magnesium stearate, zinc stearate, stearic acid, glyceryl monostearate, glyceryl palmitostearate.
The Serratipeptidase enteric preparation creatively adopts the eutectic composition with low melting point as a dispersion medium to disperse the Serratipeptidase, thereby not only ensuring the dispersion uniformity, but also avoiding the damage of high temperature to the Serratipeptidase, and simultaneously having the accessibility of solidifying into particles.
The embodiment of the invention also provides a preparation method of the serrapeptase enteric-coated preparation, which comprises the following steps:
s1 preparation of medicinal liquid
Adding the menthol, the polyethylene glycol and the cetyl alcohol ester wax into a constant-temperature water bath kettle according to the prescription amount, controlling the temperature not to exceed 38 ℃, continuously stirring until the menthol, the polyethylene glycol and the cetyl alcohol ester wax are completely melted, controlling the stirring speed to be 100rpm, adding the serrapeptase according to the prescription amount, and continuously stirring for 10min until the raw materials are completely and uniformly dispersed for later use.
S2, wet granulation
And (3) putting the filling agent and the disintegrating agent with the formula amount into a wet granulating machine, stirring for 2min at a stirring speed of 120rpm, adding the liquid medicine prepared in the step S1 into a wet granulating pot, maintaining the stirring speed of 120rpm, and controlling the liquid adding time to be 50-70S. And (4) starting granulation, controlling the stirring speed to be 150rpm, the shearing speed to be 1200rpm, the granulating time to be 5min, and discharging. And (5) carrying out wet granulation by adopting a 20-mesh sieve.
Putting wet particles into a fluidized bed, connecting an air source of the fluidized bed into a cold trap, controlling the inlet air temperature to be 0-10 ℃ and the air volume to be 400-600 m3And/s, cold drying for 10min, and discharging.
And (3) detecting the granularity: the proportion of the dry particles with the particle size of 40-120 meshes is 60-80%.
The dry particles of the serrapeptase are put into a mixer, and then the magnesium stearate with the prescription amount is put into the mixer to be mixed, the mixing speed is 12rpm, and the mixing time is 3 min.
S3 filling capsule
And (3) filling by using a capsule filling machine, selecting a No. 2 enteric-coated capsule shell, wherein the capsule filling amount is 220mg (+/-7.5%), and the filling speed is controlled to be 1200-1600 granules/min.
The method for preparing the serrapeptase enteric-coated preparation is different from the conventional preparation process of the serrapeptase, creatively adopts the eutectic composition with low melting point as a dispersion medium to disperse the serrapeptase, and the serrapeptase is subjected to wet granulation and then is cooled and dried to form solid particles. The process does not relate to a heating process above normal temperature, does not relate to any chemical reaction, is superior to a direct mixing process, can ensure that the small-size raw material serrapeptase is uniformly dispersed, can avoid the damage of high temperature to the serrapeptase, and is favorable for being solidified into particles, thereby ensuring the stability of the content of the product. In addition, the invention fully considers the instability of serrapeptase in a gastric acid environment, so that enteric capsules are adopted for protection, and in order to ensure the stability of the filling process and the uniformity of the content of the product, the invention adopts a mode of controlling the particle size of dry particles (the proportion of the particle size between 40 meshes and 120 meshes is 60-80 percent), improves the filling process, and can prepare the product with good stability. Therefore, the serrapeptase enteric preparation can be used for treating symptoms such as swelling, thick sputum and difficult expectoration, and has good treatment effect.
Example 1
Prescription:
raw and auxiliary materials | Dosage of |
Serrapeptase | 100g |
Menthol crystal | 50g |
Polyethylene glycol | 150g |
Cetyl alcohol ester wax | 200g |
Microcrystalline cellulose | 400g |
Lactose | 1180g |
Croscarmellose sodium | 100g |
Magnesium stearate | 20g |
Preparing in batches: 1 ten thousand pills.
The process comprises the following steps:
1. preparation of medicinal solutions
Adding the menthol, the polyethylene glycol and the cetyl alcohol ester wax into a constant-temperature water bath kettle according to the prescription amount, controlling the temperature to be 28 ℃, continuously stirring until the mixture is completely liquefied, and controlling the stirring speed to be 100 rpm. Adding serrapeptase in the amount of the prescription, and continuing stirring for 10min until the raw materials are completely and uniformly dispersed for later use.
2. Wet granulation
The microcrystalline cellulose, the lactose and the croscarmellose sodium with the prescription amount are put into a wet granulator and stirred for 2min at the stirring speed of 120 rpm. And adding the drug-containing eutectic composition solution in the last step into a wet granulation pot, maintaining the stirring speed at 120rpm, and controlling the liquid adding time for 60 s. And (4) starting granulation, controlling the stirring speed to be 150rpm, the shearing speed to be 1200rpm, the granulation time to be 5min, and discharging. And (5) carrying out wet granulation by adopting a 20-mesh sieve.
Putting wet particles into a fluidized bed, introducing cold hydrazine into an air source of the fluidized bed, controlling the air inlet temperature to be 0-10 ℃ and the air quantity to be 400-600 m3And/s, cold drying for 10min, and discharging.
Detection of dry particle size of serrapeptase: 66% of the total amount of the powder is 40-120 meshes.
The dry particles of serrapeptase are put into a mixer, and then the magnesium stearate with the prescription amount is put into the mixer to be mixed, the mixing speed is 12rpm, and the mixing time is 3 min.
3. Filling in
And (3) filling by using a capsule filling machine, wherein a No. 2 enteric-coated capsule shell is selected, the capsule filling amount is 220mg (+/-7.5%), and the filling speed is 1200-1600 granules/min.
The components contained in the single particle capsules prepared in this example were as follows:
raw and auxiliary materials | Content (c) of |
Serrapeptase | 10mg |
Menthol crystal | 5mg |
Polyethylene glycol | 15mg |
Cetyl alcohol ester wax | 20mg |
Microcrystalline cellulose | 40mg |
Lactose | 118mg |
Croscarmellose sodium | 10mg |
Magnesium stearate | 2mg |
Example 2
The procedure was as in example 1 except for the following.
Detecting the particle size of the dry particles of serrapeptase: 72 percent of the mixture of 40 to 120 meshes. The components contained in the single particle capsules prepared in this example were as follows:
raw and auxiliary materials | Dosage of |
Serrapeptase | 100g |
Menthol crystal | 50g |
Polyethylene glycol | 150g |
Cetyl alcohol ester wax | 200g |
Microcrystalline cellulose | 400g |
Lactose | 1180g |
Carboxymethylstarch sodium salt | 105g |
Stearic acid | 15g |
Example 3
The procedure was as in example 1 except for the following.
Detection of dry particle size of serrapeptase: 48 percent of the mixture of 40 to 120 meshes. The components contained in the single particle capsules prepared in this example were as follows:
raw and auxiliary materials | Dosage of |
Serrapeptases | 100g |
Menthol crystal | 30g |
Polyethylene glycol | 90g |
Cetyl alcohol ester wax | 120g |
Microcrystalline cellulose | 440g |
Lactose | 1300g |
Croscarmellose sodium | 100g |
Magnesium stearate | 20g |
Example 4
The procedure was as in example 1 except for the following.
Detection of dry particle size of serrapeptase: the proportion of 40-120 meshes is 90%.
The components contained in the single particle capsules prepared in this example were as follows:
raw and auxiliary materials | Dosage of |
Serrapeptase | 100g |
Menthol crystal | 70g |
Polyethylene glycol | 210g |
Cetyl alcohol ester wax | 280g |
Microcrystalline cellulose | 360g |
Lactose | 1060g |
Croscarmellose sodium | 100g |
Magnesium stearate | 20g |
Examples 5 and 6 and comparative examples 1 to 2
The procedure was as in example 1 except for the following.
Menthol crystal | Polyethylene glycol | Cetyl alcohol ester wax | Melting Point | |
Example 5 | 200g | 150g | 50g | 38℃ |
Example 6 | 150g | 100g | 150g | 35℃ |
Comparative example 1 | 40g | 120g | 240g | 47℃ |
Comparative example 2 | 10g | 90g | 300g | 53℃ |
The process comprises the following steps:
example 5 detection of dry particle size of serrapeptase: 65% of 40-120 meshes;
example 6 detection of dry particle size of serrapeptase: 69 percent of the total weight of the powder is 40-120 meshes;
comparative example 1 detection of dry particle size of serrapeptase: 73% of 40-120 meshes;
comparative example 2 detection of dry particle size of serrapeptase: the content of 40-120 meshes is 64%.
It should be noted that the content of the single-particle menthol in examples 5 and 6 exceeds the current FDA regulations for a single maximum oral dose of 14mg of menthol, and therefore is not recommended.
Test example
1. Determination of content
And (3) respectively adding trichloroacetic acid, casein, anhydrous sodium carbonate and the like into the mixture in a constant-temperature water bath environment at 37 ℃ in sequence for reaction, measuring absorbance by using an ultraviolet spectrophotometer, and calculating the content.
Sample (I) | Content (80% -130%) |
Example 1 | 101.7% |
Example 2 | 103.1% |
Example 5 | 98.7% |
Example 6 | 105.3% |
Comparative example 1 | 67.4% |
Comparative example 2 | 42.5% |
Because the product is an enzyme preparation, the activity of the enzyme is affected by conditions such as temperature. As can be seen from comparison with examples 1 and 2, the content of serrapeptase in comparative examples 1 and 2 is reduced obviously, which shows that the melting point of the fusant in the production processes of the two is too high, and both the melting points exceed 40 ℃, which is not beneficial to maintaining enzyme activity.
2. Acid resistance test
The product is an enzyme preparation and cannot resist acid environment, so the product is designed into an enteric capsule preparation, and an acid resistance test is required to ensure the product quality. Referring to the 2020 version of Chinese pharmacopoeia, according to determination of dissolution and release (first method of 0931 general rule), using 500ml hydrochloric acid solution (1 g sodium chloride, 3.5ml hydrochloric acid, and water to 500ml) of sodium chloride as dissolution medium, rotating at 100rpm, operating according to the method, and taking down the rotary basket after 120 minutes.
The content of serrapeptase in each capsule was determined by the method under the content determination item, and the results are shown in table 1.
TABLE 1
Sample (I) | Single value of content | Content average value |
Example 1 | 100%、102%、99%、101%、103%、102% | 101.2% |
Example 2 | 99%、102%、99%、103%、100%、101% | 100.7% |
As can be seen from Table 1, the serrapeptase enteric preparation of the present invention meets the content requirement.
3. Content uniformity determination
The measurement method was the same as in "content measurement item" above, and the results are shown in Table 2.
TABLE 2
As can be seen from the test data in the content uniformity item, the content mean values of the example 3 and the example 4 are normal, but the filled capsule has poor stability and large batch fluctuation due to the fact that the particle size of the dry particles of the serrapeptase is not in the production requirement range, and the relative standard deviation is more than 5%.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. This need not be, nor should it be exhaustive of all embodiments. And obvious variations or modifications derived therefrom are intended to be within the scope of the invention.
Claims (10)
1. A eutectic composition, comprising the following components: menthol, polyethylene glycol, and cetyl esters wax; the mass ratio of the menthol to the polyethylene glycol to the cetyl alcohol ester wax is (1-4): (2-3): (1-4);
preferably, the mass ratio of the menthol to the polyethylene glycol and the cetyl esters wax is 1:3:4, 4:3:1 or 3:2: 3.
2. Use of the eutectic composition of claim 1 in the preparation of a pharmaceutical formulation.
3. The Serratipeptidase enteric-coated preparation is characterized by comprising the following raw materials in parts by weight:
10 parts of serrapeptase, 24-56 parts of the eutectic composition as claimed in claim 1, 142-174 parts of a filler, 10-10.5 parts of a disintegrating agent and 1.5-2 parts of a lubricant.
4. A serrapeptase enteric formulation according to claim 3, characterized in that 10 parts of serrapeptase, 40 parts of the eutectic composition, 158 parts of filler, 10.5 parts of disintegrant, 1.5 parts of lubricant; and/or
The eutectic composition accounts for 15-20% of the total mass of the raw materials of the serrapeptase enteric-coated preparation.
5. A serrapeptase enteric formulation according to claim 3 or 4, characterized in that the filler is one or more of microcrystalline cellulose, pregelatinized starch, sucrose, lactose, starch, sorbitol, mannitol; and/or
The disintegrant is one or more of croscarmellose sodium, carboxymethyl starch sodium, crospovidone and low-substituted hydroxypropyl cellulose; and/or
The lubricant is one or more of magnesium stearate, zinc stearate, stearic acid, glyceryl monostearate and glyceryl palmitostearate.
6. A process for the preparation of an enteric formulation of sertraline peptidase according to any one of claims 3 to 5 comprising the steps of:
s1, mixing the menthol, the polyethylene glycol and the cetyl alcohol ester wax according to the prescription amount, heating and keeping the temperature not to exceed 38 ℃, adding the serrapeptase after stirring and melting, and stirring uniformly to obtain liquid medicine for later use;
s2, uniformly mixing the filling agent and the disintegrating agent according to the prescription amount, adding the liquid medicine prepared in the step S1, and preparing wet granules by adopting a wet granulation process;
s3, drying the wet granules prepared in the step S2, mixing the dried wet granules with a lubricant, and filling the mixture into enteric capsule shells.
7. The method according to claim 6, wherein the speed of stirring and mixing the filler and the disintegrant in the wet granulator is 120rpm for 2min in step S2; and/or
Adding the liquid medicine prepared in the step S1 into a mixture of the filling agent and the disintegrating agent within 50-70S; and/or
During wet granulation, the stirring speed is controlled to be 150rpm, the shearing speed is controlled to be 1200rpm, and the granulation time is controlled to be 5 min.
8. The method according to claim 6 or 7, wherein in step S3, the wet granules are dried by a cold trap in a fluidized bed, the temperature of the air is controlled to 0 to 10 ℃, the air volume is controlled to 400 to 600m3/S, and the drying time is 10 min.
9. The method according to any one of claims 6 to 8, wherein in step S3, the dry particle size of the wet particles after drying is 60 to 80% in a ratio of 40 to 120 mesh; and/or
The filling rate of the capsule is 1200-1600 granules/min.
10. Use of the enteric Serratidase formulation according to any one of claims 3-5 or prepared by the method according to any one of claims 6-9 in the preparation of a medicament for treating swelling and viscous sputum.
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2293438A1 (en) * | 1974-12-03 | 1976-07-02 | Takeda Chemical Industries Ltd | Tablet comprising enzyme and polyethylene glycol - to reduce enzyme deactivation during tabletting |
US4767557A (en) * | 1985-06-28 | 1988-08-30 | The Procter & Gamble Company | Dry bleach and stable enzyme granular composition |
US4940665A (en) * | 1985-12-27 | 1990-07-10 | Showa Denko K. K. | Method for granulation of enzyme |
JP2003335662A (en) * | 2002-05-20 | 2003-11-25 | Kokandou Seiyaku Kk | Method for producing pharmaceutical composition and pharmaceutical preparation |
US20100016449A1 (en) * | 2006-12-21 | 2010-01-21 | Boehringer Ingelheim International Gmbh | Formulations with Improved Bioavailability |
-
2022
- 2022-04-14 CN CN202210413762.9A patent/CN114699516A/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2293438A1 (en) * | 1974-12-03 | 1976-07-02 | Takeda Chemical Industries Ltd | Tablet comprising enzyme and polyethylene glycol - to reduce enzyme deactivation during tabletting |
US4767557A (en) * | 1985-06-28 | 1988-08-30 | The Procter & Gamble Company | Dry bleach and stable enzyme granular composition |
US4940665A (en) * | 1985-12-27 | 1990-07-10 | Showa Denko K. K. | Method for granulation of enzyme |
JP2003335662A (en) * | 2002-05-20 | 2003-11-25 | Kokandou Seiyaku Kk | Method for producing pharmaceutical composition and pharmaceutical preparation |
US20100016449A1 (en) * | 2006-12-21 | 2010-01-21 | Boehringer Ingelheim International Gmbh | Formulations with Improved Bioavailability |
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