CN118059050A - Oral medicine with anticancer function and its processing method - Google Patents

Abstract

The invention discloses an oral medicine with an anticancer function and a processing method thereof, relating to the technical field of oral medicine processing; the components comprise: paclitaxel, hydroxypropyl methylcellulose (HPMC), xanthan gum, solvent, antiseptic, stabilizer, flavoring agent, and pH regulator; the solvent adopts polyethylene glycol (PEG) 400, the preservative adopts sodium benzoate, the stabilizer adopts vitamin E acetate, the flavoring agent adopts sugar-free mint essence, and the pH regulator adopts citric acid or sodium citrate. The oral medicine can directly act on the affected part of oral cancer through local application, so that systemic side effects are reduced; paclitaxel can inhibit division and growth of cancer cells; hydroxypropyl methylcellulose (HPMC) is used as a carrier, not only provides a slow release effect of the drug, but also increases the residence time of the drug in the oral cavity.

Description

Oral medicine with anticancer function and its processing method

Technical Field

The invention relates to the technical field of oral medicine processing, in particular to an oral medicine with an anticancer function and a processing method thereof.

Background

Along with the acceleration of modern life pace and the increasing severity of environmental pollution, the incidence of cancers is rising year by year, and becomes one of the main diseases threatening human health. Among the many types of cancer, oral cancer, due to its particular location, affects not only the chewing, verbal functions of the patient, but also the psychological and social interactions of the patient. Current methods of treating oral cancer include surgery, radiation therapy, chemotherapy, etc., but these treatments are often accompanied by major side effects and complications. Therefore, it is important to develop an oral medicine which can assist in treating oral cancer and is convenient for patients to use.

Through searching, the patent with the Chinese patent application number of CN201711310938.3 discloses an oral pharmaceutical preparation with a slow-release effect, which can be released continuously within 8 hours and still has an effective antibacterial effect within 8 hours. The pharmaceutical preparation comprises 5 to 20 parts of controlled release agent, 60 to 90 parts of forming agent and 5 to 20 parts of bactericidal medicine according to parts by mass. The oral pharmaceutical formulations in the above patents suffer from the following disadvantages: although the oral liquid has certain antibacterial capability, the oral liquid can not well inhibit proliferation of oral cancer cells, and the oral liquid needs to be improved.

Disclosure of Invention

The invention aims to solve the defects in the prior art and provides an oral medicine with an anticancer function and a processing method thereof.

In order to achieve the above purpose, the present invention adopts the following technical scheme:

An oral medicine with anticancer function comprises the following components:

5-10mg of paclitaxel, 300-500mg of hydroxypropyl methylcellulose (HPMC), 50-100mg of xanthan gum, 5-10ml of solvent, 5-10mg of preservative, 10-20mg of stabilizer, 0.5-1ml of flavoring agent and pH regulator, wherein the pH regulator is used for regulating the pH to 4.5-5.5.

Wherein, polyethylene glycol (PEG) 400 is adopted as the solvent, sodium benzoate is adopted as the preservative, vitamin E acetate is adopted as the stabilizer, sugar-free mint essence is adopted as the flavoring agent, and citric acid or sodium citrate is adopted as the pH regulator.

Preferably: the preparation method of the oral medicine with the anticancer function comprises the following steps:

Step 1: mixing paclitaxel with a small amount of polyethylene glycol (PEG) 400 to completely dissolve it to form solution a;

Step 2: slowly adding hydroxypropyl methylcellulose (HPMC) into the rest polyethylene glycol (PEG) 400, and stirring until completely dispersing to form uniform gel substance B;

Step 3: slowly adding the solution A into the gel B, and continuously stirring to ensure uniform distribution of paclitaxel;

step 4: adding xanthan gum as a thickener into the mixture, and continuing stirring until the mixture is completely fused;

Step 5: adding sodium benzoate and vitamin E acetate, and stirring;

Step6: adjusting the pH value to be in the range of 4.5-5.5 according to the requirement;

step 7: adding sugar-free mint essence as a flavoring agent, and stirring again uniformly;

Step 8: finally, the mixture is filled into capsules or pressed into tablets, and the capsules or the tablets are hermetically packaged.

Preferably: the stirring speed in the step 2 is controlled to be 50-100rpm, the stirring speed in the step 3 is controlled to be 100-120rpm, and the temperature is controlled to be 30-40 ℃ so as to ensure that HPMC and paclitaxel are fully dispersed and dissolved.

Preferably: in the step 1, the specific steps are as follows: paclitaxel is slowly added into PEG 400 at room temperature to avoid generating bubbles; stirring was performed using a magnetic stirrer at low speed until paclitaxel was completely dissolved, forming a transparent solution.

Preferably: in the step 2, the specific steps are as follows: gradually scattering HPMC into PEG 400, and uniformly increasing the stirring speed from 50rpm to 100rpm in the process to ensure that the HPMC is fully expanded; stirring was continued for at least 30min until the HPMC was completely dispersed, forming a uniform gel matrix.

Preferably: in the step 3, the specific steps are as follows: slowly adding the solution A into the gel B by using a dropper to avoid overhigh local concentration; gradually adjusting the stirring speed to 120rpm to ensure that the solution A and the gel B are fully mixed to form homogeneous medicine gel.

Preferably: in the step 4, the specific steps are as follows: slowly sieving the pre-mixed xanthan gum into the medicinal gel to prevent caking; the stirring speed was increased to 150rpm and stirred for at least 15min until the xanthan gum was completely dispersed and incorporated into the gel system.

Preferably: in the step 5, the specific steps are as follows: firstly, dissolving sodium benzoate in a small amount of PEG 400, and then adding the sodium benzoate into the medicinal gel; then adding vitamin E acetate, and stirring for 5min to ensure uniform distribution of all components.

Preferably: in the step 6, the specific steps are as follows: measuring the pH value of the gel by using a precise pH meter, and gradually adding citric acid or sodium citrate for adjustment; stirring fully after each addition until the pH value is stabilized within a target range;

In the step 7, the specific steps are as follows: slowly dripping sugar-free peppermint essence into the medicinal gel while stirring at 20-50rpm to prevent separation; stirring is controlled at 5-10min to ensure that essence and other components are fully mixed and improve taste.

Preferably: the components comprise:

Paclitaxel 8mg, hydroxypropyl methylcellulose (HPMC) 400mg, xanthan gum 70mg, solvent 8ml, antiseptic 6mg, stabilizer 12mg, flavoring agent 0.7ml, and pH regulator, wherein the pH regulator is used for regulating pH to 5.0.

Wherein, polyethylene glycol (PEG) 400 is adopted as the solvent, sodium benzoate is adopted as the preservative, vitamin E acetate is adopted as the stabilizer, sugar-free mint essence is adopted as the flavoring agent, and citric acid or sodium citrate is adopted as the pH regulator.

The beneficial effects of the invention are as follows:

1. The oral medicine can directly act on the affected part of oral cancer through local application, so that systemic side effects are reduced; paclitaxel can inhibit division and growth of cancer cells; hydroxypropyl methylcellulose (HPMC) is used as a carrier, not only provides a slow release effect of the medicine, but also increases the residence time of the medicine in the oral cavity; through adding xanthan gum, the medicine has good adhesiveness and is not easy to be washed by saliva; in addition, the medicine ensures the stability and safety of the medicine by adjusting the pH value and adding the stabilizer; the use of the sugar-free mint essence improves the medication experience of patients.

Drawings

FIG. 1 is a flow chart of a method for processing an oral drug with anticancer function according to the present invention;

Fig. 2 is a graph showing the comparison of the effects of the oral cavity medicine with anticancer function prepared by different schemes.

Detailed Description

The technical scheme of the invention is further described in detail below with reference to the specific embodiments.

Example 1:

An oral medicine with anticancer function, which comprises the following components:

5-10mg of paclitaxel, 300mg of hydroxypropyl methylcellulose (HPMC), 50mg of xanthan gum, 5ml of solvent, 5mg of preservative, 10mg of stabilizer, 0.5ml of flavoring agent and pH regulator, wherein the pH regulator is used for regulating the pH to 4.5.

Wherein, polyethylene glycol (PEG) 400 is adopted as the solvent, sodium benzoate is adopted as the preservative, vitamin E acetate is adopted as the stabilizer, sugar-free mint essence is adopted as the flavoring agent, and citric acid or sodium citrate is adopted as the pH regulator.

The preparation method of the oral medicine comprises the following steps:

Step 1: mixing paclitaxel with a small amount of polyethylene glycol (PEG) 400 to completely dissolve it to form solution a;

Step 2: slowly adding hydroxypropyl methylcellulose (HPMC) into the rest polyethylene glycol (PEG) 400, and stirring until completely dispersing to form uniform gel substance B;

Step 3: slowly adding the solution A into the gel B, and continuously stirring to ensure uniform distribution of paclitaxel;

step 4: adding xanthan gum as a thickener into the mixture, and continuing stirring until the mixture is completely fused;

Step 5: adding sodium benzoate and vitamin E acetate, and stirring;

step 6: adjusting the pH value to 4.5 according to the requirement;

step 7: adding sugar-free mint essence as a flavoring agent, and stirring again uniformly;

Step 8: finally, the mixture is filled into capsules or pressed into tablets, and the capsules or the tablets are hermetically packaged.

Wherein the stirring speed in the step 2 is controlled to be 50-100rpm, the stirring speed in the step 3 is controlled to be 100-120rpm, and the temperature is controlled to be 30-40 ℃, so as to ensure that HPMC and paclitaxel are fully dispersed and dissolved.

In the step 1, the specific steps are as follows: paclitaxel is slowly added into PEG 400 at room temperature to avoid generating bubbles; stirring at low speed by using a magnetic stirrer until paclitaxel is completely dissolved to form transparent solution;

In the step 2, the specific steps are as follows: gradually scattering HPMC into PEG 400, and uniformly increasing the stirring speed from 50rpm to 100rpm in the process to ensure that the HPMC is fully expanded; stirring is continued for at least 30min until HPMC is completely dispersed to form a uniform gel matrix;

In the step 3, the specific steps are as follows: slowly adding the solution A into the gel B by using a dropper to avoid overhigh local concentration; gradually adjusting the stirring speed to 120rpm to ensure that the solution A and the gel B are fully mixed to form homogeneous medicine gel.

In the step 4, the specific steps are as follows: slowly sieving the pre-mixed xanthan gum into the medicinal gel to prevent caking; the stirring speed was increased to 150rpm and stirred for at least 15min until the xanthan gum was completely dispersed and incorporated into the gel system.

In the step 5, the specific steps are as follows: firstly, dissolving sodium benzoate in a small amount of PEG 400, and then adding the sodium benzoate into the medicinal gel; then adding vitamin E acetate, and stirring for 5min to ensure uniform distribution of all components.

In the step 6, the specific steps are as follows: measuring the pH value of the gel by using a precise pH meter, and gradually adding citric acid or sodium citrate for adjustment; after each addition, stirring was sufficient until the pH stabilized within the target range.

In the step 7, the specific steps are as follows: slowly dripping sugar-free peppermint essence into the medicinal gel while stirring at 20-50rpm to prevent separation; stirring is controlled at 5-10min to ensure that essence and other components are fully mixed and improve taste.

Example 2:

An oral medicine with anticancer function, which comprises the following components:

Paclitaxel 8mg, hydroxypropyl methylcellulose (HPMC) 400mg, xanthan gum 70mg, solvent 8ml, antiseptic 6mg, stabilizer 12mg, flavoring agent 0.7ml, and pH regulator, wherein the pH regulator is used for regulating pH to 5.0.

Wherein, polyethylene glycol (PEG) 400 is adopted as the solvent, sodium benzoate is adopted as the preservative, vitamin E acetate is adopted as the stabilizer, sugar-free mint essence is adopted as the flavoring agent, and citric acid or sodium citrate is adopted as the pH regulator.

The preparation method of the oral medicine comprises the following steps:

Step 1: mixing paclitaxel with a small amount of polyethylene glycol (PEG) 400 to completely dissolve it to form solution a;

Step 2: slowly adding hydroxypropyl methylcellulose (HPMC) into the rest polyethylene glycol (PEG) 400, and stirring until completely dispersing to form uniform gel substance B;

Step 3: slowly adding the solution A into the gel B, and continuously stirring to ensure uniform distribution of paclitaxel;

step 4: adding xanthan gum as a thickener into the mixture, and continuing stirring until the mixture is completely fused;

Step 5: adding sodium benzoate and vitamin E acetate, and stirring;

Step6: adjusting the pH value to be in the range of 4.5-5.5 according to the requirement;

step 7: adding sugar-free mint essence as a flavoring agent, and stirring again uniformly;

Step 8: finally, the mixture is filled into capsules or pressed into tablets, and the capsules or the tablets are hermetically packaged.

Wherein the stirring speed in the step 2 is controlled to be 50-100rpm, the stirring speed in the step 3 is controlled to be 100-120rpm, and the temperature is controlled to be 30-40 ℃, so as to ensure that HPMC and paclitaxel are fully dispersed and dissolved.

In the step 1, the specific steps are as follows: paclitaxel is slowly added into PEG 400 at room temperature to avoid generating bubbles; stirring at low speed by using a magnetic stirrer until paclitaxel is completely dissolved to form transparent solution;

In the step 2, the specific steps are as follows: gradually scattering HPMC into PEG 400, and uniformly increasing the stirring speed from 50rpm to 100rpm in the process to ensure that the HPMC is fully expanded; stirring is continued for at least 30min until HPMC is completely dispersed to form a uniform gel matrix;

In the step 3, the specific steps are as follows: slowly adding the solution A into the gel B by using a dropper to avoid overhigh local concentration; gradually adjusting the stirring speed to 120rpm to ensure that the solution A and the gel B are fully mixed to form homogeneous medicine gel.

In the step 4, the specific steps are as follows: slowly sieving the pre-mixed xanthan gum into the medicinal gel to prevent caking; the stirring speed was increased to 150rpm and stirred for at least 15min until the xanthan gum was completely dispersed and incorporated into the gel system.

In the step 5, the specific steps are as follows: firstly, dissolving sodium benzoate in a small amount of PEG 400, and then adding the sodium benzoate into the medicinal gel; then adding vitamin E acetate, and stirring for 5min to ensure uniform distribution of all components.

In the step 6, the specific steps are as follows: measuring the pH value of the gel by using a precise pH meter, and gradually adding citric acid or sodium citrate for adjustment; after each addition, stirring was sufficient until the pH stabilized within the target range.

In the step 7, the specific steps are as follows: slowly dripping sugar-free peppermint essence into the medicinal gel while stirring at 20-50rpm to prevent separation; stirring is controlled at 5-10min to ensure that essence and other components are fully mixed and improve taste.

Example 3:

An oral medicine with anticancer function, which comprises the following components:

5-10mg of paclitaxel, 500mg of hydroxypropyl methylcellulose (HPMC), 100mg of xanthan gum, 10ml of solvent, 10mg of preservative, 20mg of stabilizer, 1ml of flavoring agent and pH regulator, wherein the pH regulator is used for regulating the pH to 5.5.

Wherein, polyethylene glycol (PEG) 400 is adopted as the solvent, sodium benzoate is adopted as the preservative, vitamin E acetate is adopted as the stabilizer, sugar-free mint essence is adopted as the flavoring agent, and citric acid or sodium citrate is adopted as the pH regulator.

The preparation method of the oral medicine comprises the following steps:

Step 1: mixing paclitaxel with a small amount of polyethylene glycol (PEG) 400 to completely dissolve it to form solution a;

Step 2: slowly adding hydroxypropyl methylcellulose (HPMC) into the rest polyethylene glycol (PEG) 400, and stirring until completely dispersing to form uniform gel substance B;

Step 3: slowly adding the solution A into the gel B, and continuously stirring to ensure uniform distribution of paclitaxel;

step 4: adding xanthan gum as a thickener into the mixture, and continuing stirring until the mixture is completely fused;

Step 5: adding sodium benzoate and vitamin E acetate, and stirring;

Step6: adjusting the pH value to be in the range of 4.5-5.5 according to the requirement;

step 7: adding sugar-free mint essence as a flavoring agent, and stirring again uniformly;

Step 8: finally, the mixture is filled into capsules or pressed into tablets, and the capsules or the tablets are hermetically packaged.

Wherein the stirring speed in the step 2 is controlled to be 50-100rpm, the stirring speed in the step 3 is controlled to be 100-120rpm, and the temperature is controlled to be 30-40 ℃, so as to ensure that HPMC and paclitaxel are fully dispersed and dissolved.

In the step 1, the specific steps are as follows: paclitaxel is slowly added into PEG 400 at room temperature to avoid generating bubbles; stirring at low speed by using a magnetic stirrer until paclitaxel is completely dissolved to form transparent solution;

In the step 2, the specific steps are as follows: gradually scattering HPMC into PEG 400, and uniformly increasing the stirring speed from 50rpm to 100rpm in the process to ensure that the HPMC is fully expanded; stirring is continued for at least 30min until HPMC is completely dispersed to form a uniform gel matrix;

In the step 3, the specific steps are as follows: slowly adding the solution A into the gel B by using a dropper to avoid overhigh local concentration; gradually adjusting the stirring speed to 120rpm to ensure that the solution A and the gel B are fully mixed to form homogeneous medicine gel.

In the step 4, the specific steps are as follows: slowly sieving the pre-mixed xanthan gum into the medicinal gel to prevent caking; the stirring speed was increased to 150rpm and stirred for at least 15min until the xanthan gum was completely dispersed and incorporated into the gel system.

In the step 5, the specific steps are as follows: firstly, dissolving sodium benzoate in a small amount of PEG 400, and then adding the sodium benzoate into the medicinal gel; then adding vitamin E acetate, and stirring for 5min to ensure uniform distribution of all components.

In the step 6, the specific steps are as follows: measuring the pH value of the gel by using a precise pH meter, and gradually adding citric acid or sodium citrate for adjustment; after each addition, stirring was sufficient until the pH stabilized within the target range.

In the step 7, the specific steps are as follows: slowly dripping sugar-free peppermint essence into the medicinal gel while stirring at 20-50rpm to prevent separation; stirring is controlled at 5-10min to ensure that essence and other components are fully mixed and improve taste.

Pharmacodynamics study:

The oral medicament of the invention performs a series of pharmacodynamic studies under laboratory conditions. The in vitro cell culture technology is adopted, oral cancer cell lines (such as SCC-4, SCC-9 and the like) are exposed to medicines with different concentrations, and the cell survival rate is detected by an MTT method, so that the medicine can obviously inhibit proliferation of oral cancer cells, and the IC50 (half inhibition concentration) is 0.5-1 mug/ml. Furthermore, it was found by flow cytometry analysis that the cell cycle of the drug-treated group was blocked in the G2/M phase and the apoptosis rate was significantly increased, indicating that the anticancer mechanism of paclitaxel was preserved and exerted.

Preclinical safety evaluation:

Before the clinical trial of human body, the medicine of the invention is subjected to preclinical safety evaluation. Different doses of drug were administered to mice and rats by acute toxicity test and sub-chronic toxicity test. The results show that no significant toxic reaction was observed and no serious adverse reactions occurred with the drug of the present invention at the recommended dose. Meanwhile, the irritation research on the oral mucosa shows that the medicine has good biocompatibility and does not cause irritation or anaphylactic reaction of the mucosa.

Comparison test:

according to the protocol of examples 1-3, oral medications were prepared separately, the prepared oral medications were tested, and the test structure was evaluated to make the following conclusion:

From the above, the oral medicine prepared by the scheme of example 2 has better efficacy.

The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.

Claims (10)

1. An oral medicine with anticancer function, characterized in that the components comprise:

5-10mg of paclitaxel, 300-500mg of hydroxypropyl methylcellulose (HPMC), 50-100mg of xanthan gum, 5-10ml of solvent, 5-10mg of preservative, 10-20mg of stabilizer, 0.5-1ml of flavoring agent and pH regulator, wherein the pH regulator is used for regulating pH to 4.5-5.5;

Wherein, polyethylene glycol (PEG) 400 is adopted as the solvent, sodium benzoate is adopted as the preservative, vitamin E acetate is adopted as the stabilizer, sugar-free mint essence is adopted as the flavoring agent, and citric acid or sodium citrate is adopted as the pH regulator.

2. The oral drug with anticancer function according to claim 1, wherein the preparation method of the oral drug with anticancer function comprises the following steps:

Step 1: mixing paclitaxel with a small amount of polyethylene glycol (PEG) 400 to completely dissolve it to form solution a;

Step 2: slowly adding hydroxypropyl methylcellulose (HPMC) into the rest polyethylene glycol (PEG) 400, and stirring until completely dispersing to form uniform gel substance B;

Step 3: slowly adding the solution A into the gel B, and continuously stirring to ensure uniform distribution of paclitaxel;

step 4: adding xanthan gum as a thickener into the mixture, and continuing stirring until the mixture is completely fused;

Step 5: adding sodium benzoate and vitamin E acetate, and stirring;

Step6: adjusting the pH value to be in the range of 4.5-5.5 according to the requirement;

step 7: adding sugar-free mint essence as a flavoring agent, and stirring again uniformly;

Step 8: finally, the mixture is filled into capsules or pressed into tablets, and the capsules or the tablets are hermetically packaged.

3. The anticancer oral drug according to claim 2, wherein the stirring speed in step 2 is controlled to be 50-100rpm, the stirring speed in step 3 is controlled to be 100-120rpm, and the temperature is controlled to be 30-40 ℃ to ensure adequate dispersion and dissolution of HPMC and paclitaxel.

4. An oral cavity medicine with anticancer function according to claim 3, wherein in the step 1, the specific steps are: paclitaxel is slowly added into PEG 400 at room temperature to avoid generating bubbles; stirring was performed using a magnetic stirrer at low speed until paclitaxel was completely dissolved, forming a transparent solution.

5. The anticancer oral medicine according to claim 4, wherein in the step2, the specific steps are as follows: gradually scattering HPMC into PEG 400, and uniformly increasing the stirring speed from 50rpm to 100rpm in the process to ensure that the HPMC is fully expanded; stirring was continued for at least 30min until the HPMC was completely dispersed, forming a uniform gel matrix.

6. The anticancer oral medicine according to claim 5, wherein in the step 3, the specific steps are: slowly adding the solution A into the gel B by using a dropper to avoid overhigh local concentration; gradually adjusting the stirring speed to 120rpm to ensure that the solution A and the gel B are fully mixed to form homogeneous medicine gel.

7. The anticancer oral medicine according to claim 6, wherein in the step 4, the specific steps are: slowly sieving the pre-mixed xanthan gum into the medicinal gel to prevent caking; the stirring speed was increased to 150rpm and stirred for at least 15min until the xanthan gum was completely dispersed and incorporated into the gel system.

8. The anticancer oral medicine according to claim 7, wherein in the step 5, the specific steps are as follows: firstly, dissolving sodium benzoate in a small amount of PEG 400, and then adding the sodium benzoate into the medicinal gel; then adding vitamin E acetate, and stirring for 5min to ensure uniform distribution of all components.

9. The oral medicine with anticancer function according to claim 8, wherein in the step 6, the specific steps are: measuring the pH value of the gel by using a precise pH meter, and gradually adding citric acid or sodium citrate for adjustment; stirring fully after each addition until the pH value is stabilized within a target range;

In the step 7, the specific steps are as follows: slowly dripping sugar-free peppermint essence into the medicinal gel while stirring at 20-50rpm to prevent separation; stirring is controlled at 5-10min to ensure that essence and other components are fully mixed and improve taste.

10. An oral drug with anticancer function according to any one of claims 1 to 9, wherein the components include:

Paclitaxel 8mg, hydroxypropyl methylcellulose (HPMC) 400mg, xanthan gum 70mg, solvent 8ml, antiseptic 6mg, stabilizer 12mg, flavoring agent 0.7ml, and pH regulator, wherein the pH regulator is used for regulating pH to 5.0;

Wherein, polyethylene glycol (PEG) 400 is adopted as the solvent, sodium benzoate is adopted as the preservative, vitamin E acetate is adopted as the stabilizer, sugar-free mint essence is adopted as the flavoring agent, and citric acid or sodium citrate is adopted as the pH regulator.