CN117045663A - Use of combined GCs triamcinolone acetonide enemas in the treatment of immune checkpoint inhibitor-related immune enteritis - Google Patents
Use of combined GCs triamcinolone acetonide enemas in the treatment of immune checkpoint inhibitor-related immune enteritis Download PDFInfo
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
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- A61K9/0031—Rectum, anus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
The invention discloses an application of combined GCs triamcinolone acetonide enema in the treatment of immune checkpoint inhibitor-related immune enteritis. According to clinical test cases, the invention proves that the combined (triamcinolone acetonide) enema administration of the GCs methylprednisolone can be beneficial to the improvement of the immune enteritis related to the immune checkpoint inhibitor, so that the combined GCs (triamcinolone acetonide) enema can be used in the related fields of the immune checkpoint inhibitor, such as the immune enteritis related to the immune checkpoint inhibitor, and the like; the invention opens up a new application for GCs (triamcinolone acetonide) enema administration, provides a new treatment method for immune enteritis related to immune checkpoint inhibitor, and has good clinical application prospect. The effectiveness and the safety of the combined medication scheme provided by the invention are fully verified clinically; is easy to be accepted by patients and has unique advantages.
Description
Technical Field
The invention relates to an application of combined GCs triamcinolone acetonide enema in immune checkpoint inhibitor related immune enteritis treatment, belonging to the technical field of biological medicine.
Background
Tumor immune checkpoint inhibitor (immune-checkpoint inhibitors, ICIs) treatment is prone to eliciting ICIs-related immune enteritis. Typically occurring within 6 to 8 weeks after initiation of tumor immunotherapy, the incidence is about 10-14%. ICIs-related immune enteritis has specificity in terms of mechanism of occurrence, clinical manifestation and method of treatment, compared to other types of enteritis (e.g. ulcerative colitis, bacterial enteritis, ischemic necrotizing enteritis, etc.).
The pathogenesis is that: ICIs-related immune enteritis is caused by abnormal activation of the immune system, rather than an infection or inflammation-related immune response (other common pathogenesis of enteritis). The pathogenesis of this is related to the mechanism of action of immune checkpoint inhibitor drugs. Immune checkpoint inhibitor drugs enhance the ability to attack tumor cells by blocking the interaction of immune checkpoint molecules (e.g., PD-1, PD-L1 or CTLA-4), activating the immune system. However, this immune activity may also cause the immune system to attack normal tissues, including the intestinal mucosa, causing enteritis.
Differences in the pathogenesis of ICIs-related immune enteritis also lead to histopathological differences from other enteritis. ICIs-related immune enteritis is typically pathologically manifested by lymphocyte infiltration of intestinal mucosa, lymphofollicular hyperplasia, and nonspecific inflammatory reactions. Other enteritis is mostly caused by erosion of intestinal mucosa, ulcer formation, inflammatory cell infiltration and tissue destruction.
The clinical manifestations are those of diarrhea or colitis, including watery diarrhea, abdominal pain, and acute abdomen, among others, although they are common with other types of enteritis. However, compared with other enteritis, the symptoms are lighter, and ICIs-related immune enteritis usually shows higher severity classification when occurring, and if the anti-inflammatory treatment is not active, the death and disability rate is high, and serious life-threatening complications such as toxic megacolon, intestinal ischemia, intestinal perforation and the like are easy to occur. Relevant guidelines for the clinical management of currently more authoritative ICIs toxicity grade the severity of immune checkpoint inhibitor-related immune enteritis, which is classified as 5. Mild (G1): defecation exceeds baseline for less than 4 times daily, but without symptoms of colitis; moderate (G2): defecation exceeds the baseline for 4-6 times every day, and has colonitis symptoms, but does not affect daily life; severe (G3-4): defecation exceeds the baseline for more than 6 times every day, and has colonitis symptoms, affects daily life, has unstable hemodynamics, needs hospitalization, or has other serious complications (such as intestinal ischemia, perforation and toxic colon); and G5: death. Meanwhile, most of patients with ICIs related immune enteritis are tumor patients, and the patients with the ICIs related immune enteritis have poorer general basic conditions such as nutrition, immunity, psychology and the like, and are more prone to occurrence of serious complications of the whole body than other patients with enteritis, rather than being limited to the intestinal tract.
Intolerance or inefficiency of conventional enteritis treatment methods are more common in patients with ICIs-related immune enteritis. First, other enteritis is usually caused by infection, inflammation or autoimmunity, and the treatment method mainly aims at the etiology or inducement. For example, for enteritis caused by infection, it may be desirable to use antibiotics or antiviral drugs. Whereas immune checkpoint inhibitor-related enteritis is caused by the use of immune checkpoint inhibitor drugs, the treatment approach is mainly to modulate or deactivate drugs and to treat inflammatory reactions associated with abnormal activation of the immune system. Secondly, ICIs-related immune enteritis tends to be severe in onset, which makes effective treatments (e.g. fluid supplementation, immunomodulators, symptomatic support therapy, etc.) for other less severe enteritis of little benefit in this disease. Meanwhile, most patients with ICIs-related immune enteritis have poor general basic conditions, and often cannot tolerate treatment modes aiming at other severe enteritis, such as operation treatment, large-dose fluid infusion, immune regulator, large-dose anti-inflammatory treatment and the like.
Currently guidelines and clinical experience still recommend systemic (oral or intravenous) treatment of large doses of Glucocorticoids (GCs) for ICIs-related immune enteritis, most guidelines recommend the use of large doses of prednisolone/methylprednisolone (1-2 mg/kg/day) orally or intravenously for grade 2 or higher colitis; when level 2 or higher colitis did not improve within 2-3 days, hormone treatment continued and the addition of infliximab or vedolizumab was suggested. However, this treatment regimen has the following problems: 1) The treatment period is long, the symptoms are slowly relieved and easy to relapse under the maintenance of high-dose hormone of a patient, and the treatment time is required to be 4-6 weeks; 2) The dosage of the whole body is large, the immunosuppression risk exists, and the method is contrary to the principle of immunotherapy; 3) The hormone response rate is low, and for some patients, symptoms are not improved or even continuously aggravated after the large-dose hormone is impacted for 2-3 days, and the biological preparation with high immunity inhibition is needed to be considered. Therefore, there is a need for optimization of this therapeutic regimen to achieve higher hormone response rates and therapeutic efficacy, avoiding the potential for immunosuppression following high-dose high-duration hormone therapy.
Enema refers to an external treatment method by filling liquid medicine into rectum or colon and achieving the aim of treatment through intestinal mucosa absorption. The medicine can be directly absorbed in intestinal tracts, so that the blood concentration of a lesion part is improved, meanwhile, the medicine directly acts on the ulcer surface, avoids the damage of gastric acid, plays roles of local anti-inflammation and ulcer surface protection, can quickly promote inflammation absorption and ulcer healing, and has the characteristics of safety, effectiveness, simplicity, convenience, practicability, less adverse reaction and the like.
Triamcinolone acetonide is a topical-acting predominantly glucocorticoid with powerful and long lasting anti-inflammatory effects, but there is currently no report on its use for the treatment of ICIs-related immune enteritis.
Disclosure of Invention
The purpose of the invention is that: aiming at the technical problem that the existing hormone is adopted to treat the ICis related to the immune enteritis, the invention provides the application of combined cortisol intravenous and enema administration in treating the ICis related to the immune enteritis, and the combined administration mode can make up for the limitation of the two in each administration, so that the combined administration mode has clinical advantages, firstly, the enema administration can directly enter the pathological tissues at the far end of the colorectal, locally transport a large amount of medicines, help reduce the exposure level of systemic medicines, further lower the intravenous administration amount and avoid the systemic immunosuppression caused by the intravenous administration with a large dosage; secondly, systemic intravenous administration can make up for uneven drug distribution caused by high folding and collapse of colorectal epithelium in the single enema administration, thereby improving the therapeutic effect.
In order to achieve the aim, the invention provides application of methylprednisolone combined triamcinolone acetonide enema in preparation of medicines for treating immune checkpoint inhibitor-related immune enteritis.
Preferably, the drug is administered by systemic administration in combination with topical administration.
Preferably, the methylprednisolone is administered systemically and the triamcinolone acetonide is administered topically.
Preferably, the systemic administration is intravenous administration and/or oral administration, and the topical administration is enema administration.
Compared with the prior art, the invention has the following beneficial effects:
1. according to clinical test cases, the combined GCs (triamcinolone acetonide) enema can be favorable for improving the immune enteritis related to the immune checkpoint inhibitor, so that the combined GCs (triamcinolone acetonide) enema can be used in the related fields of immune enteritis related to the immune checkpoint inhibitor and the like, and a novel medicine and treatment thought are provided for treating the immune enteritis related to the immune checkpoint inhibitor; the invention opens up a new application for GCs (triamcinolone acetonide) enema treatment, provides a new treatment method for immune enteritis related to immune checkpoint inhibitor, and has good clinical application prospect.
2. In the invention, glucocorticoid treatment is combined with local enema for the whole body, and the advantages are complementary; through local clysis, GCs directly enters into pathological tissues at the far end of colorectal, the local drug concentration is high, the drug exposure level of the whole body is low, the local inflammation control effect is good, the rapid decrement of the whole body GCs treatment is realized, and the adverse reaction and the immunosuppression effect of the whole body of GCs are reduced; the systemic intravenous administration can make up for uneven drug distribution caused by high folding and collapse of colorectal epithelium in enema administration, and further improve the curative effect; the two are combined, so that the advantages of the two can be fully exerted, the limitations are mutually compensated, and the effect of 1+1 & gt2 is achieved.
3. The invention optimizes the GCs treatment scheme of ICIS related immune enteritis, and fully considers the interference of the immunosuppression effect of anti-inflammatory drugs on anti-tumor treatment while trying to improve the curative effect and the response rate of patients; the combined GCs local enema treatment can effectively control intestinal inflammation, has small immunosuppression effect on the whole body compared with a biological agent, and can further reduce adverse effects of systemic GCs treatment on anti-tumor treatment of patients by accelerating symptom relief and reducing treatment time, thereby realizing comprehensive optimization of treatment scheme.
4. The combined GCs triamcinolone acetonide enema provided by the invention is safe and effective, has few adverse reactions on the whole body, and has fully verified effectiveness and safety clinically; is easy to be accepted by patients and has unique advantages.
Detailed Description
In order to make the present invention more comprehensible, preferred embodiments accompanied with the present invention are described in detail below.
The test methods used in the following examples are conventional methods unless otherwise specified; the materials, reagents and the like used, unless otherwise specified, are those commercially available.
Example 1 combined triamcinolone acetonide enema accelerates symptomatic relief and improves therapeutic efficacy
Clinical cases of combined triamcinolone acetonide enema:
the formula of the medicine comprises the following steps: 1. triamcinolone acetonide enema drug: 100ml of 0.9% -sodium chloride solution and 1ml of triamcinolone acetonide injection containing 40mg of triamcinolone acetonide.
6 patients with immune checkpoint inhibitor-related immune enteritis were selected, and given a combined triamcinolone acetonide enema treatment with their informed consent. Patients were first given methylprednisolone intravenously, with gradual increments of up to 500mg/d (within 3-5 days) depending on the patient's condition, and enema was administered on the day of highest dose. When in clysis, the patient takes the left lateral position, lifts the buttocks by 10cm, adopts a drip dripping method, adopts a sputum suction tube to replace a steel tube to be inserted into the anus by 25-35 cm, slowly inputs medicine liquid, and orders the patient to adopt the knee-chest position. The temperature of the liquid medicine is maintained at about 38 ℃, and the speed of liquid input is regulated for 60 minutes for one drop or regulated according to the tolerance degree of the patient. Shaking up enema to avoid precipitation of medicinal liquid. During the operation, the patient should be asked whether the patient has uncomfortable feeling while the operation is performed. After clysis, the patient is ordered to lie in bed for 2 hours, the patient is instructed to change body position according to different parts of the disease, the patient is ordered to be unable to go out of bed, and the clysis liquid is kept for a long time as far as possible. After the enema tube drawing, the patient is assisted to take the supine position after resting for 2min, the patient is helped to lightly press the abdomen, the patient is massaged anticlockwise for 10 times, and the patient is instructed to rest for 30min and then can be taken out of bed for movement.
Patients were graded for disease severity before (at admission) and during (at maximum intravenous dose) treatment for 7d in combination with enema drug treatment, respectively, to observe treatment effects. Severity was classified as 5 altogether. Mild (G1): defecation exceeds baseline for less than 4 times daily, but without symptoms of colitis; moderate (G2): defecation exceeds the baseline for 4-6 times every day, and has colonitis symptoms, but does not affect daily life; severe (G3-4): defecation exceeds the baseline for more than 6 times every day, and has colonitis symptoms, affects daily life, has unstable hemodynamics, needs hospitalization, or has other serious complications (such as intestinal ischemia, perforation and toxic colon); and G5: death. Table 1 shows the treatment regimen (including intravenous doses and enema doses) for 6 patients, and the severity grade before and after treatment. It can be found that 40 mg/day of triamcinolone acetonide is added, the local retention enema is used for remarkably relieving symptoms of diarrhea and abdominal pain of patients (table 1), and the local enema combined with cortisol can help to accelerate the symptom relief and improve the treatment effect.
TABLE 1 improved colonitis manifestations such as diarrhea and abdominal pain after combined triamcinolone acetonide retention enema based on Methanolone intravenous administration
MT：malignant tumor；ICIs：immune-checkpoint inhibitors；ENEM：enema；GC：glucocorticoid； a : grading the severity of the illness of the patient at the time of admission; b : when the medicine is admitted, after comprehensive evaluation by doctors, intravenous methylprednisolone administration is started, and the dosage is increased because symptom relief is not obvious, wherein the value is the maximum dosage of GC administration; c : the patient's severity was graded on the day of GC maximum dosing; d : on the day of maximum GCC dose, enemas were added; e : grading the severity of the illness of the patient after 7d of combined enema treatment; G0G 0 f : clinically cured, the patient has no diarrhea and no colonitis symptoms.
Comparative example 1
The formula of the medicine comprises the following steps: 1. triamcinolone acetonide enema drug: 100ml of 0.9% -sodium chloride solution and 1ml of triamcinolone acetonide injection containing 40mg of triamcinolone acetonide.
1 patient with immune checkpoint inhibitor-related immune enteritis is selected, and the patient is subjected to combined triamcinolone acetonide enema treatment by intravenous administration of the methylprednisolone under the informed consent. Patients were first given with methylprednisolone intravenous administration, gradually increasing to 240mg/d (within 3-5 days) depending on the condition, with the highest dose being given on the day. When in clysis, the patient takes the left lateral position, lifts the buttocks by 10cm, adopts a drip dripping method, adopts a sputum suction tube to replace a steel tube to be inserted into the anus by 25-35 cm, slowly inputs medicine liquid, and orders the patient to adopt the knee-chest position. The temperature of the liquid medicine is maintained at about 38 ℃, and the speed of liquid input is regulated for 60 minutes for one drop or regulated according to the tolerance degree of the patient. Shaking up enema to avoid precipitation of medicinal liquid. During the operation, the patient should be asked whether the patient has uncomfortable feeling while the operation is performed. After clysis, the patient is ordered to lie in bed for 2 hours, the patient is instructed to change body position according to different parts of the disease, the patient is ordered to be unable to go out of bed, and the clysis liquid is kept for a long time as far as possible. After the enema tube drawing, the patient is assisted to take the supine position after resting for 2min, the patient is helped to lightly press the abdomen, the patient is massaged anticlockwise for 10 times, and the patient is instructed to rest for 30min and then can be taken out of bed for movement.
The severity of the illness before treatment of the patient is graded as G3, the severity of the illness is graded as G3 after 3-5 days of pure intravenous administration (gradually increasing to 240 mg/d), and the illness is not improved. The severity of the disease is classified as G1 after the enema medicine is added, and the disease is obviously improved.
Comparative example 2
The formula of the medicine comprises the following steps: 1. triamcinolone acetonide enema drug: 100ml of 0.9% -sodium chloride solution and 1ml of triamcinolone acetonide injection containing 40mg of triamcinolone acetonide.
1 patient with immune checkpoint inhibitor-related immune enteritis is selected, and the patient is subjected to combined triamcinolone acetonide enema treatment by intravenous administration of the methylprednisolone under the informed consent. Patients were first given with methylprednisolone intravenous administration, gradually increasing to 80mg/d (within 3-5 days) depending on the condition, with the highest dose being given on the day. When in clysis, the patient takes the left lateral position, lifts the buttocks by 10cm, adopts a drip dripping method, adopts a sputum suction tube to replace a steel tube to be inserted into the anus by 25-35 cm, slowly inputs medicine liquid, and orders the patient to adopt the knee-chest position. The temperature of the liquid medicine is maintained at about 38 ℃, and the speed of liquid input is regulated for 60 minutes for one drop or regulated according to the tolerance degree of the patient. Shaking up enema to avoid precipitation of medicinal liquid. During the operation, the patient should be asked whether the patient has uncomfortable feeling while the operation is performed. After clysis, the patient is ordered to lie in bed for 2 hours, the patient is instructed to change body position according to different parts of the disease, the patient is ordered to be unable to go out of bed, and the clysis liquid is kept for a long time as far as possible. After the enema tube drawing, the patient is assisted to take the supine position after resting for 2min, the patient is helped to lightly press the abdomen, the patient is massaged anticlockwise for 10 times, and the patient is instructed to rest for 30min and then can be taken out of bed for movement.
The severity of the illness before treatment of patients is classified as G2, the severity of the illness after 3-5 days of pure intravenous administration (gradually increased to 240 mg/d) is classified as G1, and the illness is slightly improved. The severity of the disease is graded as G0 after the enema medicine is added, the disease is obviously improved, and the clinical cure standard is reached.
Comparative example 3
The formula of the medicine comprises the following steps: 1. triamcinolone acetonide enema drug: 100ml of 0.9% -sodium chloride solution and 1ml of triamcinolone acetonide injection containing 40mg of triamcinolone acetonide.
1 patient with immune checkpoint inhibitor-related immune enteritis is selected, and the patient is subjected to combined triamcinolone acetonide enema treatment by intravenous administration of the methylprednisolone under the informed consent. Patients were first given with methylprednisolone intravenous administration, gradually increasing to 120mg/d (within 3-5 days) depending on the condition, with the highest dose being given on the day. When in clysis, the patient takes the left lateral position, lifts the buttocks by 10cm, adopts a drip dripping method, adopts a sputum suction tube to replace a steel tube to be inserted into the anus by 25-35 cm, slowly inputs medicine liquid, and orders the patient to adopt the knee-chest position. The temperature of the liquid medicine is maintained at about 38 ℃, and the speed of liquid input is regulated for 60 minutes for one drop or regulated according to the tolerance degree of the patient. Shaking up enema to avoid precipitation of medicinal liquid. During the operation, the patient should be asked whether the patient has uncomfortable feeling while the operation is performed. After clysis, the patient is ordered to lie in bed for 2 hours, the patient is instructed to change body position according to different parts of the disease, the patient is ordered to be unable to go out of bed, and the clysis liquid is kept for a long time as far as possible. After the enema tube drawing, the patient is assisted to take the supine position after resting for 2min, the patient is helped to lightly press the abdomen, the patient is massaged anticlockwise for 10 times, and the patient is instructed to rest for 30min and then can be taken out of bed for movement.
The severity of the illness before treatment of the patient is graded as G3, the severity of the illness is graded as G3 after 3-5 days of pure intravenous administration (gradually increasing to 120 mg/d), and the illness is not improved. The severity of the disease is classified as G1 after the enema medicine is added, and the disease is obviously improved.
Comparative example 4
The formula of the medicine comprises the following steps: 1. triamcinolone acetonide enema drug: 100ml of 0.9% -sodium chloride solution and 1ml of triamcinolone acetonide injection containing 40mg of triamcinolone acetonide.
1 patient with immune checkpoint inhibitor-related immune enteritis is selected, and the patient is subjected to combined triamcinolone acetonide enema treatment by intravenous administration of the methylprednisolone under the informed consent. Patients were first given with methylprednisolone intravenous administration, gradually increasing to 500mg/d (within 3-5 days) depending on the condition, with the highest dose being given on the day. When in clysis, the patient takes the left lateral position, lifts the buttocks by 10cm, adopts a drip dripping method, adopts a sputum suction tube to replace a steel tube to be inserted into the anus by 25-35 cm, slowly inputs medicine liquid, and orders the patient to adopt the knee-chest position. The temperature of the liquid medicine is maintained at about 38 ℃, and the speed of liquid input is regulated for 60 minutes for one drop or regulated according to the tolerance degree of the patient. Shaking up enema to avoid precipitation of medicinal liquid. During the operation, the patient should be asked whether the patient has uncomfortable feeling while the operation is performed. After clysis, the patient is ordered to lie in bed for 2 hours, the patient is instructed to change body position according to different parts of the disease, the patient is ordered to be unable to go out of bed, and the clysis liquid is kept for a long time as far as possible. After the enema tube drawing, the patient is assisted to take the supine position after resting for 2min, the patient is helped to lightly press the abdomen, the patient is massaged anticlockwise for 10 times, and the patient is instructed to rest for 30min and then can be taken out of bed for movement.
The severity of the illness before treatment of patients is classified as G3, the severity of the illness after 3-5 days of pure intravenous administration (gradually increased to 500 mg/d) is classified as G1, and the illness is obviously improved. The severity of the disease is graded as G0 after the enema medicine is added, the disease is further improved, and the clinical cure standard is reached.
Comparative example 5
The formula of the medicine comprises the following steps: 1. triamcinolone acetonide enema drug: 100ml of 0.9% -sodium chloride solution and 1ml of triamcinolone acetonide injection containing 40mg of triamcinolone acetonide.
1 patient with immune checkpoint inhibitor-related immune enteritis is selected, and the patient is subjected to combined triamcinolone acetonide enema treatment by intravenous administration of the methylprednisolone under the informed consent. Patients were first given with methylprednisolone intravenous administration, gradually increasing to 40mg/d (within 3-5 days) depending on the condition, with the highest dose being given on the day. When in clysis, the patient takes the left lateral position, lifts the buttocks by 10cm, adopts a drip dripping method, adopts a sputum suction tube to replace a steel tube to be inserted into the anus by 25-35 cm, slowly inputs medicine liquid, and orders the patient to adopt the knee-chest position. The temperature of the liquid medicine is maintained at about 38 ℃, and the speed of liquid input is regulated for 60 minutes for one drop or regulated according to the tolerance degree of the patient. Shaking up enema to avoid precipitation of medicinal liquid. During the operation, the patient should be asked whether the patient has uncomfortable feeling while the operation is performed. After clysis, the patient is ordered to lie in bed for 2 hours, the patient is instructed to change body position according to different parts of the disease, the patient is ordered to be unable to go out of bed, and the clysis liquid is kept for a long time as far as possible. After the enema tube drawing, the patient is assisted to take the supine position after resting for 2min, the patient is helped to lightly press the abdomen, the patient is massaged anticlockwise for 10 times, and the patient is instructed to rest for 30min and then can be taken out of bed for movement.
The severity of the illness before treatment of the patient is graded as G2, the severity of the illness is graded as G2 after 3-5 days of pure intravenous administration (gradually increasing to 40 mg/d), and the illness is not improved. The severity of the disease is graded as G0 after the enema medicine is added, the disease is obviously improved, and the clinical cure standard is reached.
Comparative example 6
The formula of the medicine comprises the following steps: 1. triamcinolone acetonide enema drug: 100ml of 0.9% -sodium chloride solution and 1ml of triamcinolone acetonide injection containing 40mg of triamcinolone acetonide.
1 patient with immune checkpoint inhibitor-related immune enteritis was selected and subjected to triamcinolone acetonide enema treatment with informed consent. When in clysis, the patient takes the left lateral position, lifts the buttocks by 10cm, adopts a drip dripping method, adopts a sputum suction tube to replace a steel tube to be inserted into the anus by 25-35 cm, slowly inputs medicine liquid, and orders the patient to adopt the knee-chest position. The temperature of the liquid medicine is maintained at about 38 ℃, and the speed of liquid input is regulated for 60 minutes for one drop or regulated according to the tolerance degree of the patient. Shaking up enema to avoid precipitation of medicinal liquid. During the operation, the patient should be asked whether the patient has uncomfortable feeling while the operation is performed. After clysis, the patient is ordered to lie in bed for 2 hours, the patient is instructed to change body position according to different parts of the disease, the patient is ordered to be unable to go out of bed, and the clysis liquid is kept for a long time as far as possible. After the enema tube drawing, the patient is assisted to take the supine position after resting for 2min, the patient is helped to lightly press the abdomen, the patient is massaged anticlockwise for 10 times, and the patient is instructed to rest for 30min and then can be taken out of bed for movement.
The severity of the illness state of the patient before treatment is graded as G2, the severity of the illness state after treatment by adopting an enema medicine is graded as G1, and the illness state is obtained.
While the invention has been described with respect to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (4)
1. Application of methylprednisolone in combination with triamcinolone acetonide enema in preparing medicine for treating immune checkpoint inhibitor-related immune enteritis is provided.
2. The use according to claim 1, wherein the medicament is administered by systemic administration in combination with topical administration.
3. The use of claim 2 wherein the methylprednisolone is administered systemically and the triamcinolone is administered topically.
4. Use according to claim 2 or 3, wherein the systemic administration is intravenous and/or oral administration and the topical administration is enema administration.
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| CN202311216938.2A CN117045663A (en) | 2023-09-20 | 2023-09-20 | Use of combined GCs triamcinolone acetonide enemas in the treatment of immune checkpoint inhibitor-related immune enteritis |
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| CN202311216938.2A CN117045663A (en) | 2023-09-20 | 2023-09-20 | Use of combined GCs triamcinolone acetonide enemas in the treatment of immune checkpoint inhibitor-related immune enteritis |
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