CN-121971590-A - Pharmaceutical composition for preventing and treating oropharyngeal mucosa injury caused by radiotherapy and chemotherapy

CN121971590ACN 121971590 ACN121971590 ACN 121971590ACN-121971590-A

Abstract

The invention relates to the technical field of sludge conditioning agents, in particular to a pharmaceutical composition for preventing and treating oropharyngeal mucosal injury caused by chemoradiotherapy, which comprises forsythin, ophiopogon root total saponin, L-glutamine, famciclovir, yeast beta-glucan, recombinant human epidermal growth factor, glutathione and glycine, and can prevent and treat oropharyngeal mucosal injury caused by chemoradiotherapy. The invention has the advantages of multicomponent synergistic effect, prevention and treatment effects, no incompatibility, good tolerance, enhanced mucous membrane adhesion, reduced administration frequency, various dosage forms, adaptation to different injury degrees and medication scenes, and comprehensive satisfaction of clinical prevention and control requirements.

Inventors

XIANG SHENGXIA
Yu Xinao
YAN JIAYU
TANG LIPING
ZOU XINYI
HE LIFANG
PAN YAN
ZHOU TIECHENG
LIU HAI
SUN GUANGWEI

Assignees

四川省中西医结合医院

Dates

Publication Date: 20260505
Application Date: 20260113

Claims (10)

1. The pharmaceutical composition for preventing and treating the oropharyngeal mucosa injury caused by chemoradiotherapy is characterized by comprising, by weight, 30-50% of core active components and auxiliary materials, wherein the auxiliary materials comprise, by weight, 5-12 parts of forsythin, 8-15 parts of ophiopogon root total saponins, 15-25 parts of L-glutamine, 2-5 parts of famciclovir, 3-8 parts of yeast beta-glucan, 0.001-0.005 part of recombinant human epidermal growth factor (rhEGF), 2-6 parts of Glutathione (GSH) and 3-7 parts of glycine.
2. The pharmaceutical composition for preventing and treating oropharyngeal mucosal injury caused by chemoradiotherapy according to claim 1, wherein the purity of forsythin in the core active component is more than or equal to 98%, the purity of ophiopogon root total saponin is more than or equal to 95%, the content of ruscogenin is more than or equal to 25%, the purity of L-glutamine is more than or equal to 99%, the water solubility is more than or equal to 50g/100mL, the content of famciclovir Wei Chundu is more than or equal to 99%, the dissolution rate is more than or equal to 98% (30 min), the molecular weight of yeast beta-glucan is 10000-50000Da, the specific activity of recombinant human epidermal growth factor is more than or equal to 5.0X10 5 U/mg, the purity is more than or equal to 99.5%, the purity of glutathione is more than or equal to 99%, the purity of glycine is more than or equal to 99%, and the water solubility at room temperature is more than or equal to 25g/100mL.
3. The pharmaceutical composition for preventing and treating oropharyngeal mucosal injury caused by chemoradiotherapy according to claim 1, wherein the core active component further comprises 1-3 parts of dipotassium glycyrrhizinate.
4. The pharmaceutical composition for preventing and treating oral and pharyngeal mucosal injury caused by chemoradiotherapy according to claim 1, wherein the formulation of the composition is collutory, oral gel or buccal tablet, the pH of the collutory is 6.5-7.2, the viscosity of the oral gel is 15000-25000 mPa.s, and the disintegration time of the buccal tablet is 15-25min.
5. The pharmaceutical composition for preventing and treating oropharyngeal mucosal injury caused by chemoradiotherapy according to claim 1, wherein the auxiliary materials comprise bioadhesive auxiliary materials, moisturizing auxiliary materials, dissolution assisting auxiliary materials and stabilizing agents, wherein the bioadhesive auxiliary materials are chitosan or sodium carboxymethyl cellulose, the moisturizing auxiliary materials are glycerol or sorbitol, the dissolution assisting auxiliary materials are polyethylene glycol 400 or polyethylene glycol 600, and the stabilizing agents are vitamin E or sodium sulfite.
6. The pharmaceutical composition for preventing and treating oral and pharyngeal mucosal injury caused by chemoradiotherapy according to claim 1, wherein the core active components comprise 8 parts of forsythin, 10 parts of ophiopogon root total saponin, 18 parts of L-glutamine, 3 parts of famciclovir, 5 parts of yeast beta-glucan, 0.003 part of recombinant human epidermal growth factor (rhEGF), 4 parts of glutathione and 5 parts of glycine.
7. The pharmaceutical composition for preventing and treating oropharyngeal mucosa injury caused by chemoradiotherapy according to claim 1, wherein the forsythin is prepared by adopting an ethanol reflux extraction method, the extraction solvent is ethanol with the volume fraction of 60-70%, the feed liquid ratio is 1:8-1:12, the extraction temperature is 60-70 ℃, the extraction time is 2-3 hours, the extraction is 2 times, the combined extract is subjected to reduced pressure concentration and macroporous resin purification, the total ophiopogonin is prepared by adopting a water extraction and alcohol precipitation method, the feed liquid ratio is 1:10-1:15, the extraction temperature is 80-90 ℃, the extraction time is 1.5-2 hours, the extraction is 2 times, the combined extract is concentrated to the relative density of 1.10-1.15, the ethanol is added to the volume fraction of 70%, the mixture is left for 12 hours, the mixture is filtered and concentrated, and then purified by a polyamide column, and the glutathione is synthesized by adopting an enzyme method.
8. A method for preparing a pharmaceutical composition for preventing and treating oropharyngeal mucosal injury caused by radiotherapy and chemotherapy according to any one of claims 1 to 7, comprising the following steps: S1, accurately weighing each core active component according to the proportion, mixing forsythin and ophiopogon root total saponins, adding 3-5 times of dissolution auxiliary materials, stirring and dissolving at a constant temperature of 50-60 ℃ for 15-20min, and stirring at a rotating speed of 150-200r/min to obtain uniform traditional Chinese medicine active liquid, and detecting no undissolved particles after dissolving; S2, taking glutathione and glycine, dissolving with a small amount of purified water, adding a traditional Chinese medicine active liquid, sequentially adding L-glutamine, famciclovir and yeast beta-glucan, stirring and dispersing at the normal temperature of 25-30 ℃ for 20-30min at the stirring speed of 100-150r/min, finally adding a recombinant human epidermal growth factor, stirring at the low temperature for 5-10min until the mixture is uniformly dispersed, and continuously introducing nitrogen for protection in the dispersing process to obtain a mixed active liquid; S3, adding the rest pharmaceutically acceptable auxiliary materials according to the proportion, firstly stirring for 10min at a low speed, then stirring for 20min at a high speed, fully and uniformly mixing, stirring at a rotation speed of 300-350r/min, regulating the pH of the system to 6.5-7.2, filtering and sterilizing by a microporous membrane with the thickness of 0.22 mu m, controlling the filtering pressure to be 0.1-0.15MPa, shaping according to the corresponding formulation process, and detecting the content, detecting the microbial limit and detecting the activity of the recombinant human epidermal growth factor after shaping.
9. The application of the pharmaceutical composition in preparing medicines for preventing oropharyngeal mucosa injury caused by radiotherapy and chemotherapy according to claim 1, wherein the administration time is adapted to different radiotherapy and chemotherapy schemes, administration is started 3-5 days before radiotherapy and started 1-2 days before chemotherapy for patients after radiotherapy and started 3 days before chemotherapy for patients after chemotherapy, administration modes are distinguished according to dosage forms, mouthwash is 10-15mL for each time, mouthwash is spitted out after 3-5min, the oral gel is 3-4 times daily, 0.5-1g for each time, the oral gel is accurately smeared on easily damaged parts of oropharyngeal mucosa, drinking water is not eaten within 30min after smearing, 2-3 times daily, buccal tablets are orally taken to completely disintegrate, are not chewed during the period of oral taking, 3 times daily, and the oral gel is prevented from 7-10 days after the period of radiotherapy and chemotherapy is finished.
10. The use of the pharmaceutical composition according to claim 1 for preparing medicines for treating oropharyngeal mucosal injury caused by radiotherapy and chemotherapy, wherein the medicines are precisely administered according to the division of oropharyngeal mucosal injury, the daily administration frequency is increased by 1 time compared with the preventive dosage for I-II degree injury, the gargle gargling time is prolonged to 5min, the oral gel is smeared for 1 time every 6 hours, 1 piece is taken every 6 hours, 15-20mL of gargle is used for every time for III-IV degree injury, gargling is carried out for 5-8min, 4 times daily, 1-1.5g of oral gel is smeared for 1 time every 4 hours, 2 pieces are taken every 6 hours.

Description

Pharmaceutical composition for preventing and treating oropharyngeal mucosa injury caused by radiotherapy and chemotherapy Technical Field The invention relates to the technical field of sludge conditioning agents, in particular to a pharmaceutical composition for preventing and treating oropharyngeal mucosa injury caused by radiotherapy and chemotherapy. Background Chemoradiotherapy is a core means for clinically treating malignant tumors, but lacks tissue specificity, and when killing tumor cells, the oropharynx mucosa epithelial cells are easily damaged, so that oropharynx mucosa injury is caused. The adverse reaction rate is extremely high, the incidence rate of radiotherapy patients exceeds 80%, the incidence rate of radiotherapy patients can reach more than 90%, symptoms are more manifested by congestion, edema, erosion and ulcer of mucous membrane, and severe burning pain is accompanied, dysphagia and eating disorder can be caused when severe, and even radiotherapy and chemotherapy are forced to be interrupted, so that the treatment effect is reduced, and the life quality and prognosis of patients are seriously affected. The types of drugs currently used clinically for preventing and treating the injury are limited, and obvious technical defects exist. The traditional Chinese medicine preparation mainly comprises a single anti-inflammatory and salivation promoting component, can relieve mild inflammation, but has weak mucous membrane repairing capability and poor immunoregulation effect, is difficult to cope with moderately severe injury, and western medicines such as L-glutamine and the like, which are used for repairing mucous membrane epithelium, but have poor anti-inflammatory and antiviral effects, are easy to aggravate injury due to secondary herpesvirus activation, have potential compatibility contraindication with partial radiotherapy and chemotherapy drugs, and can interfere with treatment effect. Biological agents such as recombinant human epidermal growth factor can promote mucous membrane proliferation, but has the advantages of limited single use curative effect, high price and poor clinical popularity, and most of the existing compound preparations are simple component superposition, do not form a synergistic effect system, can only act on a certain symptom, and cannot realize the combination of prevention and treatment. In addition, most of the medicines have poor adhesion to mucous membranes, short residence time, frequent administration, poor pain relieving effect, difficulty in rapidly improving discomfort of patients and high recurrence rate. In summary, the prior art has the multiple defects of single symptomatic, poor component cooperativity, prevention and treatment of disjoint, insufficient safety, slow effect, easy recurrence and the like, and cannot meet the clinical requirement of high-efficiency prevention and control of oropharyngeal mucosa injury caused by radiotherapy and chemotherapy, and a pharmaceutical composition with multi-component cooperativity, multi-target effect, prevention and treatment effects, high safety and adaptation to clinical requirements is needed. Disclosure of Invention (One) solving the technical problems Aiming at the defects of the prior art, the invention provides a pharmaceutical composition for preventing and treating oropharyngeal mucosa injury caused by radiotherapy and chemotherapy. (II) technical scheme A pharmaceutical composition for preventing and treating oropharyngeal mucosa injury caused by chemoradiotherapy comprises, by weight, 5-12 parts of forsythin, 8-15 parts of ophiopogon root total saponin, 15-25 parts of L-glutamine, 2-5 parts of famciclovir, 3-8 parts of yeast beta-glucan, 0.001-0.005 part of recombinant human epidermal growth factor (rhEGF), 2-6 parts of Glutathione (GSH) and 3-7 parts of glycine, wherein the auxiliary material accounts for 30-50% of the total weight of the composition. Preferably, the purity of the forsythin in the core active component is more than or equal to 98%, the purity of the total saponins of the dwarf lilyturf tuber is more than or equal to 95%, the content of the lukesapogenin is more than or equal to 25%, the purity of the L-glutamine is more than or equal to 99%, the water solubility is more than or equal to 50g/100mL, the dissolution rate of the famciclovir Wei Chundu is more than or equal to 99%, the dissolution rate is more than or equal to 98% (30 min), the molecular weight of the yeast beta-glucan is 10000-50000Da, the specific activity of the recombinant human epidermal growth factor is more than or equal to 5.0x10 5 U/mg, the purity of the glutathione is more than or equal to 99%, the purity of the glycine is more than or equal to 99%, and the water solubility at room temperature is more than or equal to 25g/100mL. Preferably, the core active component further comprises 1-3 parts of dipotassium glycyrrhizinate. Preferably, the composition is in the form of collutory, oral gel or bucca