阅读说明：本技术 一种盐酸环丙沙星栓剂及其制备方法 (Ciprofloxacin hydrochloride suppository and preparation method thereof ) 是由 徐朗 沈晨 陈容 徐扬 方方 杨尚志 于 2021-09-07 设计创作，主要内容包括：本发明涉及药物制剂技术领域,特别涉及一种盐酸环丙沙星栓剂及其制备方法。以重量份计,该盐酸环丙沙星栓剂由如下原辅料组成：盐酸环丙沙星,200～250份；聚乙二醇4000,500～2000份；聚乙二醇400,200～500份；甘油,50～200份；水,10～100份。本发明具有的技术效果为：本发明盐酸环丙沙星栓剂组成简单,且刺激性小,可增加患者的依从性。(The invention relates to the technical field of medicinal preparations, in particular to a ciprofloxacin hydrochloride suppository and a preparation method thereof. The ciprofloxacin hydrochloride suppository consists of the following raw and auxiliary materials in parts by weight: 200-250 parts of ciprofloxacin hydrochloride; 500-2000 parts of polyethylene glycol 4000; 200-500 parts of polyethylene glycol; 50-200 parts of glycerol; 10-100 parts of water. The invention has the technical effects that: the ciprofloxacin hydrochloride suppository has simple composition and small irritation, and can increase the compliance of patients.)

1. The ciprofloxacin hydrochloride suppository is characterized by comprising the following raw and auxiliary materials in parts by weight:

2. the ciprofloxacin hydrochloride suppository of claim 1, which is prepared from the following raw and auxiliary materials in parts by weight:

3. the ciprofloxacin hydrochloride suppository according to claim 1 or 2, which is characterized by comprising the following raw and auxiliary materials in parts by weight:

4. a method of preparing a ciprofloxacin hydrochloride suppository as claimed in any one of claims 1 to 3, comprising the steps of:

step 1) mixing polyethylene glycol 4000 and polyethylene glycol 400, and heating to obtain a matrix in a molten state;

step 2) mixing the molten matrix with glycerol and water, and stirring;

step 3), adding ciprofloxacin hydrochloride, and stirring;

and 4) stirring the mixed materials in a vacuum state, and keeping the temperature.

5. The method according to claim 4, wherein the heating temperature in step 1) is 65 to 85 ℃.

6. The preparation method according to claim 4, wherein the stirring time in the step 2) is 15 to 20 minutes, and the stirring speed is 800 to 1000 r/min.

7. The preparation method according to claim 4, wherein the stirring time in the step 3) is 15 to 20 minutes, and the stirring speed is 30 to 35 r/min.

8. The method according to claim 4, wherein the degree of vacuum in the vacuum state in step 4) is-0.05 to-0.10 Pa, and the stirring time is 15 to 20 minutes.

9. The method according to any one of claims 4 to 8, wherein the temperature of the heat-retaining in step 4) is 55 ℃ to 65 ℃.

Technical Field

The invention relates to the technical field of medicinal preparations, in particular to a ciprofloxacin hydrochloride suppository and a preparation method thereof.

Background

The fluoroquinolone medicaments have great success in the aspect of clinical anti-infection treatment due to the high-efficiency, broad-spectrum and low-toxicity antibacterial characteristics. Ciprofloxacin hydrochloride is an excellent variety of fluoroquinolones developed in 1981 by bayer corporation, germany.

Ciprofloxacin hydrochloride with the chemical name of 1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo- (1-piperazinyl) -3-quinoline carboxylate and the molecular formula of C₁₇H₁₈FN₃O₃HCL, molecular weight 385.82, has a broad-spectrum antibacterial action, is particularly highly active against gram-negative aerobic bacteria, and has good antibacterial action in vitro against: most bacteria of the enterobacteriaceae family include Citrobacter, cloacae, Enterobacter aerogenes, Escherichia coli, Klebsiella, Proteus, Salmonella, Shigella, Vibrio, Yersinia, and the like. It also has antibacterial activity against multiple drug-resistant bacteria. Has high antibacterial activity to penicillin-resistant Neisseria gonorrhoeae, Haemophilus influenzae and Moraxella. Has antibacterial effect on most strains of Pseudomonas such as Pseudomonas aeruginosa. The product has antibacterial activity against methicillin-sensitive Staphylococcus aureus, and only has moderate antibacterial activity against Streptococcus pneumoniae, hemolytic streptococcus and enterococcus faecalis. It also has good effect on Chlamydia trachomatis, Mycoplasma, Legionella, and also has antibacterial activity on tubercle bacillus and atypical mycobacterium. Has poor antibacterial activity against anaerobes. Ciprofloxacin is a bactericide, acts on A subunit of bacterial DNA helicase to inhibit DNA synthesis and replication to cause bacterial death, and is widely used clinically.

The invention patent with publication number CN102836120A discloses a ciprofloxacin lactate suppository, which comprises the following components: ciprofloxacin lactate, 100 g; polyethylene glycol 4000, 900 g; 400g of polyethylene glycol; polyoxyethylene monostearate S-40, 200 g; tween 80, 400 g. The preparation method comprises the following steps: heating polyethylene glycol 4000 and polyethylene glycol 400 in 80 deg.C water bath to melt, adding polyoxyethylene monostearate, adding Tween 80 and ciprofloxacin lactate sieved with No. 6 sieve, stirring, maintaining the temperature at 55 deg.C, pouring into suppository mold coated with lubricant, cooling, and taking out. Each capsule contains 100mg of ciprofloxacin lactate, and the weight of each capsule is 2g, and the total weight of the capsules is 1000. However, the ciprofloxacin hydrochloride suppository prepared by the matrix has low bioavailability in organisms and more types of required matrix.

Disclosure of Invention

In view of the above, the invention provides a ciprofloxacin hydrochloride suppository and a preparation method thereof. The ciprofloxacin hydrochloride suppository has simple composition, high bioavailability and obvious curative effect.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides a ciprofloxacin hydrochloride suppository which comprises the following raw and auxiliary materials in parts by weight:

preferably, the feed additive comprises the following raw and auxiliary materials in parts by weight:

preferably, the composition comprises the following raw and auxiliary materials in parts by weight:

the invention also provides a preparation method of the ciprofloxacin hydrochloride suppository, which comprises the following steps:

step 1) mixing polyethylene glycol 4000 and polyethylene glycol 400, and heating to obtain a matrix in a molten state;

step 2) mixing the molten matrix with glycerol and water, and stirring;

step 3), adding ciprofloxacin hydrochloride, and stirring;

and 4) stirring the mixed materials in a vacuum state, and keeping the temperature.

Preferably, the heating temperature in the step 1) is 65-85 ℃.

Preferably, the stirring time in the step 2) is 15-20 minutes, and the stirring speed is 800-1000 r/min.

Preferably, the stirring time in the step 3) is 15-20 minutes, the stirring speed of the main stirring paddle is 30-35 r/min, and the rapid stirring speed is 2800-3000 r/min.

Preferably, the vacuum degree in the vacuum state in the step 4) is-0.05 to-0.10 Pa, and the stirring time is 15 to 20 minutes.

Preferably, the degree of vacuum in the vacuum state in step 4) is-0.06 Pa, and the stirring time is 15 minutes.

Preferably, the temperature for the heat preservation in step 4) is 55 ℃ to 65 ℃.

The invention provides a ciprofloxacin hydrochloride suppository and a preparation method thereof. The ciprofloxacin hydrochloride suppository consists of the following raw and auxiliary materials in parts by weight: 200-250 parts of ciprofloxacin hydrochloride; 500-2000 parts of polyethylene glycol 4000; 200-500 parts of polyethylene glycol; 50-200 parts of glycerol; 10-100 parts of water. The invention has the technical effects that: the ciprofloxacin hydrochloride suppository has simple composition and small irritation.

Detailed Description

The invention discloses a ciprofloxacin hydrochloride suppository and a preparation method thereof, and a person skilled in the art can realize the preparation by properly improving process parameters by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.

The ciprofloxacin hydrochloride suppository and the preparation method thereof provided by the invention can be purchased from the market by using raw material medicines or auxiliary materials.

The invention is further illustrated by the following examples:

example 1

(1) Prescription

TABLE 1 ciprofloxacin hydrochloride suppository formulation

Raw and auxiliary materials	1000 pills dosage (g)	Pretreatment
			Ciprofloxacin hydrochloride	222.33	N/A
Polyethylene glycol 4000	1084	Filtering with 200 meshes after melting
			Polyethylene glycol 400	351.5	200 mesh filtration
Glycerol	80.33	200 mesh filtration
			Purified water	62	N/A

(2) Preparation process

Adding polyethylene glycol 4000 and polyethylene glycol 400 into a matrix tank, heating at 80 + -5 deg.C, melting most of the solid matrix, stirring to completely melt the solid matrix, and stirring at 1000 r/min; and adding glycerol and purified water, and continuously stirring for 15-20 minutes. Adding ciprofloxacin hydrochloride with the prescription amount, and stirring for 20 minutes by a main stirring paddle at 30-35 r/min and by rapid stirring at 2800-3000 r/min. Vacuumizing the main tank to a vacuum degree of-0.06 Pa; starting stirring; stirring for 15 minutes in a vacuum state, and circularly preserving heat at 55-65 ℃. And (5) encapsulating according to the product loading.

Comparative example 1

Suppository preparation was made with reference to the matrix of patent example 1 of invention CN 102836120A.

Prescription: ciprofloxacin hydrochloride, 222.33 g; polyethylene glycol 4000, 1084 g; polyethylene glycol 400, 351.5 g; polyoxyethylene monostearate S-40, 240 g; tween 80, 480 g.

The preparation method comprises the following steps: heating polyethylene glycol 4000 and polyethylene glycol 400 in 80 deg.C water bath to melt, adding polyoxyethylene monostearate, adding Tween 80 and ciprofloxacin hydrochloride, stirring, keeping the temperature at 55 deg.C, pouring into suppository mold coated with lubricant, cooling, and taking out.

Test example vaginal mucosal irritation test

Test four sets of comparative experiments were set up, grouped as follows:

TABLE 2 prescriptions of each group of drugs (1000 dosage, unit: g)

1. Preparation of

1) Sample preparation: example 1 group of samples, comparative example 1 group of samples, matrix group of samples

2) Experimental animal species: white Japanese big ear rabbits; grade: a normal stage; sex: a female; quantity: 12, the number of the main components is 12; body weight range: 2.05-2.20kg for administration

3) Sample treatment: the above samples were taken, cut into 0.25g, and gently delivered into the vagina of a white rabbit with a smooth glass rod.

4) Grouping: test group (example 1 group, comparative example 1 group, matrix group) and normal group

2. Method of producing a composite material

Animals were fixed on their backs and the samples were gently introduced (4cm-5cm) into the vagina with a smooth glass rod, and no samples were given to the normal group.

24 hours after the last administration, the animals are killed by an air embolism method, the whole vagina is taken out after laparotomy, the longitudinal incision is carried out, and whether congestion, edema and other manifestations exist or not is observed by naked eyes for reference when pathological material drawing is carried out. Then the vagina is put into 10 percent formalin solution for fixation for more than 24 hours, tissues at two ends and 3 parts in the center of the vagina are selected for flaking, and histopathological examination is carried out after HE staining.

3. Results

TABLE 3 vaginal mucosal irritation Strength grading

Index of irritation of vaginal mucosa	Intensity of vaginal mucosa irritation response
		1<	Is free of
1-<5	Is extremely light
		5-<9	Mild degree of
9-<12	Of moderate degree
		≥12	Severe degree

The stimulation response integrals of 3 sites of 3 animals in the test group are added and divided by the total number of observation (animal number multiplied by 3) to obtain the average integral of the vaginal mucosa stimulation response in the test group. Normal group scoring methods are as above. After subtracting the average integral of the normal group from the average integral of the test group to obtain the stimulation index, the stimulation intensity was graded according to table 3.

TABLE 4 animal vaginal mucosal irritation response scores

4. And (4) conclusion:

the stimulation index of the vaginal mucosa of the experimental animal in the group of example 1 is 0.89, the stimulation index of the vaginal mucosa of the experimental animal in the group of comparative example 1 is 4.9, and the stimulation index of the matrix group to the vaginal mucosa of the experimental animal is 0.11; the sequence of the irritancy intensity of the test samples to the vaginal mucosa was: matrix group < example 1 group < comparative example 1 group. It can be seen that the suppository of example 1 is less irritating to the vaginal mucosa than the suppository of comparative example 1.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.