CN109700757A - A kind of Mesalazine and the compound preparation of paracetamol and application thereof - Google Patents

Abstract

The present invention provides a kind of compound preparation containing Mesalazine and paracetamol, the compound preparation is enema, is made of Mesalazine 4g, paracetamol 0.2g~0.65g, metal-chelator 0.04g~0.1g, antioxidant 0.1g~0.5g, preservative 0.01g~0.2g, suspending agent 0.1g~0.4g, pH adjusting agent 0.1g~0.4g, purified water to 60g.The present invention also provides the preparation method of above-mentioned compound preparation and purposes.Stable product quality and homogeneity is good, improves the validity and safety of patient medication.For the existing good therapeutic effect of ulcerative colitis, and there is preferable analgesic activity.

Description

A kind of Mesalazine and the compound preparation of paracetamol and application thereof

Technical field

The invention belongs to field of pharmaceutical preparations, are related to a kind of compound preparation containing Mesalazine and paracetamol And application thereof.

Background technique

Ulcerative colitis is a kind of chronic nonspecific inflammatory bowel disease that the cause of disease is not still fully aware of, lesion limitation In colorectal mucosa and submucosa.It is main with mucus pus and blood stool, abdominal pain and enteron aisle diffusivity, transmural inflammation and ulcer Clinical manifestation, the course of disease is very long, normal recurrent exerbation, if can not be treated in time, can seriously affect patient work and life.

The Western medicine for the treatment of ulcerative colitis mainly has aminosalicylic acids, glucocorticoids, immunosuppressor at present Class and probiotics class etc..Aminosalicylic acids common drug has sulfasalazine, Mesalazine etc., is ulcerative colitis Gently, the first choice of moderate patient activity phase.

Common medicine of the Mesalazine as treatment ulcerative colitis, due to its excellent therapeutic effect, in world wide Inside it is widely used.But it takes orally Mesalazine for a long time easily liver to be caused to damage, and in clinical use, still accidental abdomen The adverse reactions such as discomfort, headache and dizzy, courbature, arthralgia.The patent of Publication No. CN101129389B discloses one kind and controls The suppository and preparation method thereof of colitis is treated, which contains poly- 40 ester of hydrogen-oxygen of Mesalazine, stearic acid and other pharmaceutic adjuvants, Not stimulating gastrointestinal road, be avoided that first pass effect of the drug to the damage and liver of liver to drug, rectally, convenient for absorbing hair Wave that drug effect, cheap, stability is good.The patent of Publication No. CN108553554A discloses one kind and contains paracetamol Suppository, the invention avoid traditional suppository administration after lead to the problem of blood concentration peak height, peak valley, reach continued administration, prevent The purpose of recurrent exerbation.Mesalazine and paracetamol have very exact clinical treatment in clinical application many years Effect, but compound preparation is made in the two drug, make it that can treat ulcerative colitis and reduction of patient abdominal pain or bad Bring pain is reacted, is at home and abroad not reported.

Summary of the invention

It is an advantage of the invention to provide a kind of compound enema containing Mesalazine and paracetamol, The enema homogeneity is good, stability is high.It is a further object of the invention to provide a kind of sides for preparing above-mentioned compound preparation Method.Yet another object of the invention is that providing the purposes of above-mentioned compound preparation.

Technical solution of the present invention is as follows:

1. compound preparation of the invention is by Mesalazine 4g, paracetamol 0.2g~0.65g, metal-chelator 0.04g~0.1g, antioxidant 0.1g~0.5g, preservative 0.01g~0.2g, suspending agent 0.1g~0.4g, pH adjusting agent 0.1g ~0.4g, purified water to 60g form.

The compound preparation according to 1, dosage form are enema fluid.

The compound preparation according to 1, the metal-chelator are natrium adetate, and dosage is 0.04g~0.06g.

The compound preparation according to 1, the antioxidant is in sodium sulfite, sodium pyrosulfite, potassium metabisulfite One or more, dosage are 0.2g~0.35g.

The compound preparation according to 1, the preservative are selected from one or more of sodium benzoate, Potassium Benzoate, use Amount is 0.05g~0.1g.

The compound preparation according to 1, the suspending agent are selected from one or more of xanthan gum, carbomer, and dosage is 0.1g~0.2g.

The compound preparation according to 1, the pH adjusting agent are selected from one or more of sodium acetate, potassium acetate, dosage For 0.15g~0.25g.

It is of the invention the preparation method comprises the following steps:

1) the new boiling water for accounting for about total amount 80% is taken, the metal-chelator, antioxidant and preservative of recipe quantity is sequentially added, stirs It mixes to dissolution.

2) suspending agent of recipe quantity, stirring swelling are slowly added under stirring.

3) antioxidant, Mesalazine and the paracetamol of recipe quantity is added, stirs and evenly mixs.

4) homogeneous adds new boiling water to stir evenly to full dose, it is filling to obtain the final product.

Compound preparation of the invention has the advantage that compared with prior art and good effect:

1. Mesalazine is the choice drug of ulcerative colitis acute attack stage, by inhibiting leukotriene and prostaglandin Synthesis, scavenging activated oxygen adjust immune, anti-inflammatory etc. play a role.Paracetamol is acetophenone amine analgesic-antipyretic, By inhibiting the synthesis (including inhibiting prostaglandin synthetase) of prostaglandin in central nervous system and blocking pain nerve The impulsion of tip and generate analgesic activity.It is especially suitable to aspirin-sensitive or the patient for not tolerating aspirin.The present invention Compound preparation can be used to treat ulcerative colitis and reduction of patient abdominal pain or other adverse reaction brings pain Bitterly.And two kinds of drugs have synergistic effect, can enhance therapeutic effect.

2. compound preparation of the invention is enema, by rectally, part works, no first pass effect and tolerance is good It is good.

3. two kinds of drugs are compound formulation, there is specific chemical structure, single ingredient after compound preparation is made Effective dose can be guaranteed.

Specific embodiment

The present invention is further explained in the light of specific embodiments, but this should not be interpreted as to the above-mentioned theme of the present invention Range be only limitted to embodiment below.The techniques implemented on the basis of the foregoing are all within the scope of the present invention. Auxiliary material in following embodiment can be replaced with pharmaceutically acceptable similar auxiliary material, be decreased or increased.

Embodiment 1

Preparation process:

(1) the new boiling water of about 45g is taken, the natrium adetate, sodium benzoate and potassium acetate of recipe quantity are sequentially added, is stirred to molten Solution.

(2) xanthan gum and carbomer of recipe quantity, stirring swelling are slowly added under stirring.

(3) sodium sulfite, Mesalazine and the paracetamol of recipe quantity is added, stirs and evenly mixs.

(4) homogeneous adds new boiling water to stir evenly to full dose, it is filling to obtain the final product.

Embodiment 2

Preparation process:

(1) the new boiling water of about 45g is taken, sequentially adds the natrium adetate, Potassium Benzoate and potassium acetate sodium of recipe quantity, stirring is extremely Dissolution.

(2) xanthan gum and carbomer of recipe quantity, stirring swelling are slowly added under stirring.

(3) sodium pyrosulfite, Mesalazine and the paracetamol of recipe quantity is added, stirs and evenly mixs.

(4) homogeneous adds new boiling water to stir evenly to full dose, it is filling to obtain the final product.

Embodiment 3

Preparation process:

(1) the new boiling water of about 45g is taken, sequentially adds the natrium adetate, Potassium Benzoate and potassium acetate sodium of recipe quantity, stirring is extremely Dissolution.

(2) xanthan gum and carbomer of recipe quantity, stirring swelling are slowly added under stirring.

(3) potassium metabisulfite, Mesalazine and the paracetamol of recipe quantity is added, stirs and evenly mixs.

(4) homogeneous adds new boiling water to stir evenly to full dose, it is filling to obtain the final product.

Embodiment 2

One, test objective

By test, observation mouse improves situation using symptom after drug of the present invention and control group drug respectively.

Two, test material

1, test drug: drug of the present invention, Mesalazine enema fluid (registration certificate H20150127), Mesalazine bolt (traditional Chinese medicines Quasi- word H20065650), Mesalazine enteric-coated tablet (national drug standard H20020211), Mesalazine sustained release tablets (registration certificate number H20160693), Mesalazine slow-releasing granules (national drug standard H20143164).

2, animal: the healthy BALB/c mouse of 18~22g of weight, male and female dual-purpose.Mouse is handled as follows: initial stage mouse Situations such as free water, observation feed, drinking-water, defecation.7% glucan sulfuric acid is changed to after confirmation mouse health and adaptation environment Sodium solution, with induced ulcer colitis.Become free water after 5 days again.Mouse is observed in treatment process, and whether there is or not " writhing is anti- Answer ", defecation situations such as.

Three, test method

Treated BALB/c mouse 105, is randomly divided into A, B, C, D, E, F, H group, and every group 15.It tests previous It is deprived of food but not water at night.A group mouse rectally, gives drug therapy of the present invention, one time a day, 1 4g every time；B group mouse Rectally gives the treatment of commercially available Mesalazine enema fluid (registration certificate H20150127), one time a day, 1 4g every time；C group Mouse rectally gives the treatment of commercially available Mesalazine bolt (national drug standard H20065650), one time a day, 1 piece of 1g every time；D group Mouse feeding Mesalazine enteric-coated tablet (national drug standard H20020211), 3 times a day, 1 tablet once；E group mouse feeding Mesalazine Sustained release tablets (registration certificate H20160693), 4 times a day, each 1g；F group mouse feeding Mesalazine slow-releasing granules (national drug standard H20143164), 4 times a day, each 1g；H group mouse is not treated, as blank control group.Restore normal diet after administration, sees Examine whether mouse symptom of diarrhea or " writhing response " occurs.Successive administration 7 days, evening before that day equal fasting is administered every time can't help Water.In putting to death mouse with cervical dislocation for 24 hours after the last administration, abdominal cavity is opened, local rectum is taken out, carries out Histopathology inspection It looks into.

Four, test result

1, healthy BALB/c mouse occurs that stool is loose or diarrhea after 7% dextran sulfate sodium processing, under weight Drop is obvious, the visible bloody stool of naked eyes, the symptom of body distortion, abdomen contraction, crawling etc. " writhing response ".

2, for H group mouse due to not receiving treatment after the dextran sulfate sodium processing with 7%, the death rate is up to 73% (11/ 15) mouse death rate for, receiving drug therapy is then lower, respectively A group 7% (1/15), B group 13% (2/15), C group 27% (4/15), D group 27% (4/15), E group 13% (2/15), F group 20% (3/15).

3, administration group efficacy result compares

Curative effect is defined as follows:

1) complete incidence graph: excrement is normal, no hematochezia, and weight is without being decreased obviously, almost without " writhing response ", Histopathology Inspection does not find colonic mucosa inflammation, lesion and crypt damage.

2) effectively: excrement is normal, and the positive of occulting blood, weight loss slows down, and " writhing response " number is reduced, pathological tissue It learns and checks the slight colonic mucosa inflammation of discovery, lesion and crypt damage.

3) invalid: inspection result is without improvement after treating.

1 administration group curative effect of table compares

Group	Total (only)	Complete incidence graph	Effectively	In vain	Total effective rate
						A group (drug of the present invention)	15	4	9	2	86.7%
B group (Mesalazine enema fluid)	15	3	8	4	73.3%
						C group (Mesalazine bolt)	15	2	5	8	46.7%
D group (Mesalazine enteric-coated tablet)	15	1	6	8	46.7%
						E group (Mesalazine sustained release tablets)	15	3	7	5	66.7%
F group (Mesalazine slow-releasing granules)	15	2	7	6	60.0%

Five, conclusion (of pressure testing)

Can be seen that A group total effective rate according to the test result of table 1 is 86.7%, significant in efficacy to be better than remaining 5 groups.It says Bright drug of the present invention had not only had preferable analgesic effect, but also had the function of significantly treating ulcerative colitis.

Claims (8)

1. the compound preparation of a kind of Mesalazine and paracetamol, it is characterised in that: dosage form is enema fluid, the compound system Agent by Mesalazine 4g, paracetamol 0.2g~0.65g, metal-chelator 0.04g~0.1g, antioxidant 0.1g~ 0.5g, preservative 0.01g~0.2g, suspending agent 0.1g~0.4g, pH adjusting agent 0.1g~0.4g, purified water to 60g form.

2. compound preparation according to claim 1, it is characterised in that: the metal-chelator is natrium adetate, dosage For 0.04g~0.06g.

3. compound preparation according to claim 1, it is characterised in that: the antioxidant is selected from sodium sulfite, pyrosulfurous acid One or more of sodium, potassium metabisulfite, dosage are 0.2g~0.35g.

4. compound preparation according to claim 1, it is characterised in that: the preservative is selected from sodium benzoate, Potassium Benzoate One or more of, dosage is 0.05g~0.1g.

5. compound preparation according to claim 1, it is characterised in that: the suspending agent is in xanthan gum, carbomer One or more, dosage are 0.1g~0.2g.

6. compound preparation according to claim 1, it is characterised in that: the pH adjusting agent is in sodium acetate, potassium acetate One or more, dosage be 0.15g~0.25g.

7. compound preparation described according to claim 1~any one of 6 the preparation method comprises the following steps:

1) the new boiling water for accounting for about total amount 80% is taken, sequentially adds the metal-chelator, antioxidant and preservative of recipe quantity, stirring is extremely Dissolution.

2) suspending agent of recipe quantity, stirring swelling are slowly added under stirring.

3) antioxidant, Mesalazine and the paracetamol of recipe quantity is added, stirs and evenly mixs.

4) homogeneous adds new boiling water to stir evenly to full dose, it is filling to obtain the final product.

8. compound preparation described according to claim 1~any one of 6 is used to prepare the acute hair for the treatment of ulcerative colitis Make the application in drug.