CN115501229A - A Chinese medicinal composition for treating new coronary pneumonia and its preparation method - Google Patents

Abstract

The invention provides an oral preparation for treating neocoronary pneumonia, which comprises the following components in parts by mass: 100-200 parts of component A and 30-70 parts of component B, wherein the component A and the component B are different or the same protease inhibitor. The component A is as follows: a covalent inhibitor that can bind directly to the cysteine-catalytic residue of a protease (Cys 145). The component B is as follows: an inhibitor of aspartic protease. The compound preparation with the effective components of the nelmavir tablets and the ritonavir tablets can be produced without adjusting the production line of the existing oral dosage form on a large scale.

Description

A kind of oral preparation for treating new coronary pneumonia and preparation method thereof

technical field

The present disclosure relates to the field of medical technology, in particular to an oral preparation for treating COVID-19 and a preparation method thereof.

Background technique

Corona Virus Disease 2019 (COVID-19), referred to as "New Coronary Pneumonia", named by the World Health Organization as "2019 Coronavirus Disease", refers to the pneumonia caused by 2019 Novel Coronavirus infection.

For this disease, the currently commonly used drug is a combination drug packaged in combination with Naimatevir tablets and Ritonavir tablets, wherein both Naimatevir tablets and Ritonavir tablets need to be packaged separately. This leads to: 1. When preparing the combination medicine, there are special requirements for the packaging machine, and the existing production line needs to be modified, which significantly increases the production cost. 2. When the patient takes the medicine, since the two tablets are packaged separately, it is easy to cause the patient to take more or miss one of the medicines, which brings inconvenience to the non-patient.

Contents of the invention

In order to overcome the deficiencies of the prior art, the purpose of the present disclosure is to provide an oral drug that can combine the main active ingredients in the Nematervir tablet and the Ritonavir tablet in the same dosage form.

In order to achieve the above object, the present disclosure adopts the following technical solutions:

An oral preparation for treating new coronary pneumonia, in parts by mass, comprising: 100-200 parts of component A and 30-70 parts of component B, wherein, the components A and B are different or the same protease inhibitors.

The present disclosure exemplarily provides a component A, which is: a covalent inhibitor that can directly bind to the cysteine catalytic residue (Cys145) of protease.

The present disclosure exemplarily provides a component B, the component B is: an inhibitor of aspartic protease.

The present disclosure exemplarily provides a component A, the component A is: a compound of structural formula (1), and structural formula (1) is:

The present disclosure exemplarily provides a component A, and the component A is: a compound in which some groups are added, replaced or reduced on the basis of the structural formula (1).

The present disclosure exemplarily provides a component B, the component B is: the compound of structural formula (2), and the structural formula (2) is:

The present disclosure exemplarily provides a component B, and the component B is: a compound in which some groups are added, replaced or reduced on the basis of the structural formula (2).

In addition, the present disclosure also provides a preparation method for oral preparations for the treatment of new coronary pneumonia, including:

S1. Prepare additive A containing component A, and prepare additive B containing component B;

S2. Prepare/process the additive A and additive B into the target dosage form after mixing;

The component A is the component A described in any one of claims 1-3, and the component B is the component B described in any one of claims 1-3.

The present disclosure exemplarily provides a target dosage form, including: oral capsule preparations, oral tablet preparations, oral lozenge preparations, oral solution preparations, oral suspension preparations, oral syrup preparations, brewing granule preparations, and effervescent tablet preparations kind of.

The present disclosure exemplarily provides a preparation method of additive A containing component A, comprising:

First, in terms of mass percentage, prepare: 60-65% of component A, and the balance of processing aid A.

Then, additive A is prepared by mixing component A and processing aid A.

The present disclosure exemplarily provides a preparation method of additive B containing component B, comprising:

First, in terms of mass percentage, prepare: 10-20% of component B, and the balance of processing aid B.

Then, additive B is prepared by mixing component B and processing aid B.

The present disclosure exemplarily provides a preparation method of additive A, including:

First, component A, microcrystalline cellulose, flavoring agent, and disintegrant are mixed to obtain mixture A.

Then, adding a binder to the mixture A for granulation and drying to obtain the granule A; the weight loss on drying is controlled to be less than 3%.

Finally, add anti-caking agent, bulking agent, lubricant, and binder to the particulate matter A for mixing, and the additive A is obtained after mixing.

The present disclosure exemplarily provides a preparation method of additive A, including:

First, component A, microcrystalline cellulose, flavoring agent, disintegrant, and lubricant A are mixed to obtain mixture C.

Mixture C was then prepared as a sheet extrudate using a roller compaction method.

Thereafter, the flake extrudate obtained was pulverized into granules to obtain granules C.

Finally, the particle C is mixed with anticaking agent, bulking agent and lubricant B, and punched into flakes to obtain additive A.

The present disclosure exemplarily provides a flavoring agent which is at least one of white sugar, brown sugar and lactose.

The present disclosure exemplarily provides a disintegrating agent which is at least one of: sodium carboxymethyl starch, dry starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, and cross-linked sodium carboxymethyl cellulose .

The present disclosure exemplarily provides a binder that is at least one of starch, povidone, and gelatin.

The present disclosure exemplarily provides an anticaking agent which is at least one of sodium aluminosilicate, tricalcium phosphate, silicon dioxide and micronized silica gel.

The present disclosure exemplarily provides a bulking agent which is at least one of sodium bicarbonate, ammonium bicarbonate and microcrystalline cellulose.

The present disclosure exemplarily provides a lubricant A which is at least one of talc powder and magnesium stearate.

The present disclosure exemplarily provides a lubricant B which is at least one of talcum powder and magnesium stearate.

The present disclosure exemplarily provides a preparation method of additive B, including:

First, component B, carrier polymer, surfactant, glidant A are mixed to obtain mixture B.

Then, the mixture B is hot-melt extruded and granulated to obtain granules B.

Finally, the granular material B is mixed with the filler and the glidant B, and the additive B is obtained after the mixing is completed.

The present disclosure exemplarily provides a carrier polymer, including: at least one of polysaccharide polymers, polyamino acid polymers, and polyester polymers.

The present disclosure exemplarily provides a carrier polymer, which is: copovidone.

The present disclosure exemplarily provides a surfactant, including: at least one of sodium lauryl sulfate, sorbitol laurate, Tween 80, cetyltrimethylamine bromide, and sodium stearyl sulfonate .

The present disclosure exemplarily provides a glidant A, which is at least one of talc powder, micronized silica gel, and colloidal silicon dioxide.

The present disclosure exemplarily provides a glidant B, which is at least one of talc powder, micronized silica gel, colloidal silicon dioxide, and sodium fumarate stearate.

The present disclosure exemplarily provides a filler, including: at least one of calcium sulfate, calcium hydrogen phosphate, calcium carbonate, microcrystalline cellulose, and compressible starch.

The present disclosure exemplarily provides an additive A partially coated with a third substance.

The present disclosure exemplarily provides an additive B partially coated with a third substance.

The present disclosure exemplarily provides a third substance, including: at least one of gastric-soluble coating powder, enteric-soluble coating powder, and flavoring agent.

After adopting the above technical solution, the present disclosure has the following beneficial effects:

(1) The present disclosure does not need large-scale adjustment of the production line of the existing oral dosage forms to produce a compound medicine having both active ingredients of Nematervir Tablets and Ritonavir Tablets.

(2) The present disclosure overcomes the adverse consequences caused by directly mixing the Naimatevir tablets and the Ritonavir tablets by processing the active ingredients in the Naimatevir tablets and the Ritonavir tablets .

(3) The oral preparation obtained in the present disclosure has good drug release ability and human body absorption ability, and can shorten the onset time of the drug to a certain extent.

detailed description

The present disclosure will be further described in detail below in combination with embodiments. It can be understood that the specific implementation manners described here are only used to explain relevant content, rather than to limit the present disclosure.

It should be noted that, in the case of no conflict, the implementation modes and the features in the implementation modes in the present disclosure can be combined with each other. The present disclosure will be described in detail below in combination with embodiments.

Example 1

An oral preparation for treating new coronary pneumonia, in parts by mass, comprising: 150 parts of component A1 and 50 parts of component B, wherein:

Component A is:

Component B is:

The oral preparation for treating new coronary pneumonia is prepared by the following preparation method:

S1. Prepare additive A containing component A, and prepare additive B containing component B.

S2. Mix additive A and additive B as the contents of the capsule, and process it into an oral capsule preparation based on the existing capsule preparation process.

in:

The preparation method of described additive A comprises:

First, 60% of component A, 27% of microcrystalline cellulose, 6% of lactose monohydrate, and 3% of croscarmellose sodium were mixed to obtain mixture A in terms of mass percentage.

Then, in terms of mass percentage, 2% binder was added to the mixture A for granulation, and dried to obtain granule A; the weight loss on drying was controlled to be less than 3%.

Finally, in terms of mass percentage, 1% micronized silica gel and 1% magnesium stearate were added to the granule A for mixing, and the additive A was obtained after the mixing was completed.

The preparation method of the additive B comprises:

First, in terms of mass percentage, 15% of component B, 60% of copovidone, 8.4% of sorbitol laurate, and 0.5% of colloidal silicon dioxide were mixed to obtain mixture B;

Then, the mixture B is hot-melt extruded and granulated to obtain granules B;

Finally, the granule B was mixed with 15% calcium hydrogen phosphate, 0.7% sodium stearate fumarate, and 0.4% colloidal silicon dioxide in terms of mass percentage, and the additive B was obtained after mixing.

Example 2

The rest of the steps in this example are the same as in Example 1, the difference is that the preparation method of the additive A comprises:

First, in terms of mass percentage, 60% of component A, 25% of microcrystalline cellulose, 6.5% of lactose monohydrate, 5% of croscarmellose sodium, and 0.5% of magnesium stearate were carried out Mix to obtain mixture C.

Mixture C was then prepared as a sheet extrudate using a roller compaction method.

Thereafter, the flake extrudate obtained was pulverized into granules to obtain granules C.

Finally, the granule C was mixed with 1% micropowder silica gel and 2% magnesium stearate in terms of mass percentage, and punched into flakes to obtain the additive A.

Example 3

The rest of the steps in this example are the same as those in Example 2, the difference is that the additive A is coated with a common immediate-release gastric-soluble coating powder, and the weight of the coating is increased by 3%.

All the above-mentioned examples can obtain a compound capsule preparation of nematervir-ritonavir that can be mixed stably.

The rest of the dosage forms, such as: oral tablet preparations, use Additive A and Additive B as one of the components, and cooperate with the existing tabletting technology of tablet drugs or the improved technology for Additive A and Additive B to produce oral tablets.

Such as: oral buccal preparations, additive A and additive B are used as one of the components, combined with the existing buccal tablet compression technology or improved technology for additive A and additive B, to prepare oral tablets preparation.

Such as: Oral solution preparation: Prepared by dissolving Additive A and Additive B in a solvent as one of the solutes.

For example: Oral suspension preparation: Prepare Additive A and Additive B as a suspension or one of the suspensions and mix them with a solvent.

For example: Oral syrup preparation: After mixing Additive A and Additive B as the main ingredients with the existing syrup base or the syrup base adjusted according to Additive A and Additive B, use the existing syrup preparation technology or aim at Oral syrup preparations are prepared by the improved technology of additive A and additive B.

For example: brewing granule preparation: Additive A and additive B are used as the main components, and the existing brewing granule preparation technology or the improved technology for additive A and additive B are used to prepare the brewing granule preparation.

For example: effervescent tablet preparation: Additive A and additive B are used as main components, and the existing effervescent tablet preparation technology or improved technology for additive A and additive B is used to prepare effervescent tablet preparation.

In the description of this specification, descriptions referring to the terms "one embodiment/mode", "some embodiments/modes", "examples", "specific examples", or "some examples" mean that the embodiments/modes are combined The specific features, structures, materials or characteristics described in or examples are included in at least one embodiment/mode or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment/mode or example. Moreover, the described specific features, structures, materials or characteristics may be combined in any one or more embodiments/modes or examples in an appropriate manner. In addition, those skilled in the art may combine and combine different embodiments/modes or examples and features of different embodiments/modes or examples described in this specification without conflicting with each other.

It should be understood by those skilled in the art that the above-mentioned embodiments are only for clearly illustrating the present disclosure, rather than limiting the scope of the present disclosure. For those skilled in the art, other changes or modifications can be made on the basis of the above disclosure, and these changes or modifications are still within the scope of the present disclosure.

Claims (9)

1. An oral preparation for the treatment of new coronary pneumonia, characterized in that, in parts by mass, comprising: 100-200 parts of component A and 30-70 parts of component B, wherein, said component A and group Part B is for different or same protease inhibitors. 2. The oral preparation for treating new coronary pneumonia as claimed in claim 1, wherein said component A is a covalent inhibitor that can directly combine with the cysteine catalytic residue (Cys145) of protease ; The component B is an inhibitor of aspartic protease. 3. The oral preparation for the treatment of new coronary pneumonia as claimed in claim 1, wherein the component A is the compound described in the structural formula (1) or on the basis of the structural formula (1) to increase, replace, reduce part of the Group of compounds:

Component B is the compound described in structural formula (two) or the compound that increases, replaces, or reduces some groups on the basis of structural formula (two):

4. A preparation method for oral preparations for the treatment of new coronary pneumonia, characterized in that, comprising: S1. Prepare additive A containing component A, and prepare additive B containing component B; S2. Prepare/process the additive A and additive B into the target dosage form after mixing; The component A is the component A described in any one of claims 1-3, and the component B is the component B described in any one of claims 1-3. 5. The method for preparing oral preparations for the treatment of new coronary pneumonia according to claim 4, wherein the target dosage forms include: oral capsule preparations, oral tablet preparations, oral buccal preparations, oral solution preparations, oral suspension preparations , one of oral syrup preparations, brewing granule preparations, and effervescent tablet preparations. 6. The method for preparing oral preparations for the treatment of new coronary pneumonia as claimed in claim 4, wherein the preparation method of additive A containing component A comprises: First, in terms of mass percentage, prepare: 60-65% of component A, and the balance of processing aid A; Then, component A and processing aid A are mixed to prepare additive A; The preparation method of additive B containing component B comprises: First, prepare: 10-20% of component B and the balance of processing aid B in mass percentage; Then, additive B is prepared by mixing component B and processing aid B. 7. The method for preparing oral preparations for the treatment of new coronary pneumonia as claimed in claim 6, wherein the method for preparing the additive A comprises: First, mix component A, microcrystalline cellulose, flavoring agent, and disintegrant to obtain mixture A; Then, add a binder to the mixture A to granulate, and dry to obtain the granule A; the weight loss on drying is controlled to be less than 3%; Finally, add micropowder silica gel and magnesium stearate to the particulate matter A for mixing, and the additive A is obtained after mixing; The preparation method of the additive B comprises: First, mix component B, carrier polymer, surfactant, glidant A to obtain mixture B; Then, the mixture B is hot-melt extruded and granulated to obtain granules B; Finally, the particles B are mixed with the filler, the lubricant, and the glidant B, and the additive B is obtained after the mixing is completed. 8. The method for preparing oral preparations for the treatment of new coronary pneumonia as claimed in claim 6, wherein the method for preparing the additive A comprises: First, component A, microcrystalline cellulose, flavoring agent, disintegrant, magnesium stearate A are mixed to obtain mixture C; Then, the mixture C is prepared as a sheet extrudate by rolling method; Thereafter, the flake extrudate obtained is pulverized into granules to obtain granules C; Finally, the granule C is mixed with micropowder silica gel and magnesium stearate B, and punched into a flake shape to obtain the additive A; The preparation method of the additive B comprises: First, mix component B, carrier polymer, surfactant, glidant A to obtain mixture B; Then, the mixture B is hot-melt extruded and granulated to obtain granules B; Finally, the particles B are mixed with the filler, the lubricant, and the glidant B, and the additive B is obtained after the mixing is completed. 9. The method for preparing an oral preparation for treating COVID-19 according to any one of claims 7 or 8, wherein the additive A and/or the additive B are coated with a third substance.