CN104147603A - Application of novel marine algae extractive composition in preventing virus flu - Google Patents

Abstract

The invention relates to a novel marine algae extractive composition which comprises red algae extractive, a bacteriostatic agent and purified water. According to the invention, the bacteriostatic agent is added into a nasal spray, so that marine algae polyose in the marine algae extractive is prevented from degradation and the synergistic effect of auxiliary virus flu prevention and symptom alleviation is achieved, therefore, the marine algae extractive composition can effectively maintain nasal mucosa moist and is prominent in physical adjuvant therapy and flu preventing effect.

Description

The application of a kind of novel alga extractive composition in preventing viral flu

Technical field

The invention belongs to field of pharmaceutical preparations, be specifically related to the nasal spray and the preparation thereof that comprise red algae extract.

Background technology

Upper respiratory tract infection is the clinical disease that sickness rate is higher, according to expert statistics, upper respiratory tract infection 2 ~ 5 times on average occurs for each person every year, and wherein maximum is flu.The current known nearly kind more than 200 of cold virus, many just because of Pathogen category, people can not form the immunity of consolidation to them, so repeated infection.Rhinovirus is topmost virulence factor wherein.In the medicine of the preventing cold of domestic production at present, be mostly Chinese prescription and oral formulations, complicated process of preparation is used a large amount of organic solvents, to environment in preparation process; Mechanism of action is imprecise, and side effect needs further to be studied; Mouthfeel is poor, and patient compliance reduces, and therefore flu prevention seems very important.

Respiratory mucosa directly communicates with the external world, is subject to the impact of various imbedibility injurious factors.When the multiple season of catching a cold and autoimmunity reduction, keep nasal cavity moistening and unimpeded, contribute to maintain the normal physiological function of nasal membrane cilium transmission system, a large amount of virus is cleaned out to nose, Virus entry human body less and less, within viral number in nasal cavity can being reduced to the scope that nasal cavity immunity system can tackle, the final incidence rate that reduces flu, reaches the effect of preventing cold.

Active substance in Sargassum extract is combined with skin protein and is formed moisture retention gel; and it can form protecting film on the surface of skin by hydration; prevent moisture evaporation; research worker is studied the Sargassum of coastal morning and evening tides amount reproduction, finds that sulfated polysaccharide wherein has obvious moisture-keeping function.

The antiviral composition that comprises sulfated polysaccharide is provided in CN101784272A, for preventing or treat by respiratory virus infection cause or infect relevant pathological state or disease to this, described Respirovirus is selected from the group that influenza virus, paramyxovirus, adenovirus and coronavirus form; CN102652017A relates to the combination that is used as t-and/or k-carrageenin and the neuraminidase inhibitor of medicament in symptom, disease or disease that prophylactic treatment or therapeutic treatment are correlated with by influenza infection.In patent CN101678040B, provide Sargassum extract carrageenan or its mixture manufacturing for preventing or treat the application of the anti-viral pharmaceutical compositions of rhinovirus infection; Patent CN102065869A relates to and in preventative or therapeutic treatment anaphylactic disease or disease, is used as pharmaceutical composition medicine, based on a kind of Sargassum polysaccharides as the Sargassum extract of active component, for respiratory tract gastrointestinal tract or eyes are used; Can effectively prevent and treat type i allergic reaction, and can bring into play adjuvant function during to mucosa combined administration together with non-Sargassum polysaccharides therapeutic agent in addition.

The antiviral activity of the relevant Sargassum polysaccharides of above patent and act on above-mentioned patent and just have more research and report before declaring, and in the embodiment of above-mentioned patent all without the preparation process of nasal spray or other dosage forms, only have this virus test description.

Summary of the invention

For the pathogenesis of flu, the theory based on putting prevention first, the invention provides a kind of novel Sargassum extract compositions, for auxiliary treatment and preventing viral, catches a cold and improves the related symptoms that flu causes.

The active medicine that is different from other treatment flu, said composition is characterised in that the effect of the harmful substance in nasal cavity being played to physical protection, wherein Sargassum extract is red algae extract, and human body is had no side effect.

In Sargassum extract molecular structure, there is great amount of hydroxy group or carboxyl isopolarity group and sodium alginate, can form hydrogen bond with hydrone, and be usually cross-linked with each other and reticulate structure.This network structure has good viscosity and filming performance, can provide barrier to resist outside poisonous and harmful substance and nasal cavity receptors bind, and can adhere to the harmful substance entering in nasal cavity, reduce the suction volume of harmful substance, thereby auxiliary treatment and preventing cold improve the symptoms such as nasal cavity that flu causes is dryly itched, watery nasal discharge, nasal obstruction, sneeze, halitosis simultaneously.

Sargassum extract compositions of the present invention is comprised of red algae extract, antibacterial and purified water, and wherein red algae extract concentrations is 0.6 ~ 3.5 mg/mL, and described red algae extract concentrations is preferably 1. 5 ~ 3.0 mg/mL, and antibacterial concentration is 0.08 ~ 0.12mg/mL.

The preparation type of above-mentioned Sargassum extract compositions is selected from: nasal spray, nasal drop, peroral dosage form and injection type; By resisting the rhinoviral test of pesticide effectiveness, find that the effect of nasal spray will be far superior to other dosage forms, and the using conveniently of nasal spray, therefore the preparation of red algae extract of the present invention is preferably nasal spray.

Antibacterial in above-mentioned Sargassum extract compositions nasal spray is selected from glycerol, benzalkonium bromide, benzoic acid, sorbic acid, potassium sorbate, thimerosal, preferably thimerosal.

Prepare four kinds of red algae extract concentrations and be 0.5 mg/ml, 0.6 mg/ml, 1.2 mg/ml, 1.5 mg/ml, 2.0mg/ml, 2.5 mg/ml, 3.0mg/ml, 3.5 mg/ml, 3.6 mg/ml Sargassum extract compositions nasal spray solution trial results are as follows.

concentration is investigated result table

As seen from the experiment, when in Sargassum extract compositions nasal spray, red algae extract concentrations is greater than 3.5 mg/ml, solution gelation; Although in good condition while being less than 0.6 mg/ml, very good by becoming film test to detect its mobility, be difficult for forming moisture film on nasal mucosa, therefore red algae extract concentrations of the present invention is 0.6 ~ 3.5mg/ml; It is that the protection effect that plays of 1.5 ~ 3.0mg/ml is better that pharmacological evaluation detects its concentration, and therefore preferably the concentration range of red algae extract is 1.5 ~ 3.0mg/ml in Sargassum extract compositions nasal spray.

The red algae extract that the present invention is mentioned, analyze after testing, main component is the materials such as red seaweed polysaccharide, red algae fiber, sodium alginate, electrolyte, plant collagen, after comparative study, the discovery that we are surprised, the red algae extract that contains these compounding substances, has the more obvious effect that intercepts rhinovirus and flu-prevention than single carrageenan or sulfated polysaccharide; Meanwhile, the test of pesticide effectiveness we find that red algae extract compares Sargassum and mix remarkably productive as algae extracts such as Brown algae, chlorellas of algae or other single algae; Red algae extract is also a kind of mixture, except containing the single components such as a small amount of carrageenan and sulfated polysaccharide, also contains other polysaccharides; By our surprised discovery of the test of pesticide effectiveness, when the amount of red algae extract is controlled within the scope of 1.5 ~ 3.0mg/ml, compares nasal spray protection effect prepared by the Sargassum extract in same dosage range and promoted 10% ~ 15%; Single carrageenan or the sulfated polysaccharide compared in same dosage range are that nasal spray protection effect prepared by raw material has promoted 35.0% ~ 55.0%, therefore by contrast, employing red algae extract of the present invention is that raw material can be effective more fast and effectively aspect physical protection, has no side effect.

Solution pH value scope is 6.0 ~ 7.0, approaches neutrality, and solution is water white transparency thick liquid.

Sargassum extract compositions nasal spray, in preparation process, sterilization method high temperature sterilize, gaseous sterilization and sterilization by ionizing radiation etc. are investigated, all find that conventional sterilization method makes end-product PH scope not within the scope of normal physiological, we adopt and add suitable antibacterial to carry out growing of the microorganisms such as anti-bacteria.Meanwhile, the related symptoms that test antibacterial auxiliary treatment and preventing viral flu and the flu of improving cause has also played synergism.

According to nasal membrane, can tolerate pH value is 6～8 and the feature of red algae extract self preferably efficient, low toxicity, non-irritating antibacterial, investigation adds antibacterial front and back pH value and changes, and add solution state after antibacterial and add after the project such as fungistatic effect in this nasal spray, synergistic corrosion virus effect, antibacterial is selected from glycerol, benzalkonium bromide, benzoic acid, sorbic acid, potassium sorbate, thimerosal, preferably add rear pH value to change not obvious, the thimerosal that sample is stable, fungistatic effect is better, synergistic corrosion virus is effective is done antibacterial.The amount that adds thimerosal in this product is 0.08 ~ 0.12mg/mL, and the PH of gained Sargassum extract compositions nasal spray is 6.0 ~ 7.0.

The capacity of this nasal spray is every bottle of 10mL, and every spray amount is 0.10 ~ 0.12mL, and keeping mucosa dosage moistening, preventing cold is 0.60 ~ 0.72mL/ day, every day three times.

The present invention also provides the preparation technology of this red algae nasal spray to be: measure 70% volume purified water in Agitation Tank; Weighing recipe quantity red algae extract, thimerosal are fed in Agitation Tank, stir and it are all dissolved in 15 minutes; Supply purified water and be settled to full dose; Fill, 10ml/ bottle;

Leak detection, packing.

Red algae nasal spray of the present invention take have good moisture retention can and better the red algae extract of filming performance be basic components, formulation and technology is simple, good stability, and adopt animal experiment to carry out the research of effectiveness and safety aspect, red seaweed polysaccharide extract is not killed rhinovirus, affect the effect of rhinovirus replication, can not be subject to the in the situation that nose infecting cell to treat and repair at cell, be merely able to play the effect that prevention rhinovirus is invaded human body.

This product has the physicochemical property approaching with nasal cavity mucus, contributes to maintain nasal cavity normal physiological function, can moistening nasal cavity after use, contribute to the scavenging action of cilium, and can resist outside infection.Adopt the administering mode of nasal spray, good patient compliance, convenient drug administration.

The advantage of red algae extract nasal spray of the present invention is: nasal spray is compared other dosage forms, remarkably productive, and preparation is simple, easy to operate, can quantitatively use, and preparation stability of the present invention is better, uses conveniently.Red algae extractive composition nasal spray forms one deck moisturizing mucosa on nasal mucosa, compare other single compositions and obtained beyond thought physical protection effect as carrageenan, sulfated polysaccharide etc., compare Sargassum extract or other algae extracts, Sargassum extract composition effect of the present invention is more remarkable; In nasal spray of the present invention, add antibacterial, prevented the degraded of Sargassum polysaccharides in Sargassum extract, and played the synergism of auxiliary influenza and relief of symptoms; Therefore it is moistening that Sargassum extract compositions of the present invention more can effectively maintain nasal mucosa, auxiliary treatment and the preventing cold of physical property are remarkably productive.

The specific embodiment

embodiment 1the preparation of Sargassum extract compositions nasal spray

Component	Recipe quantity (g)
		Red algae extract	15g
Thimerosal	1g
		Purified water	10000 ml
Make	1000 bottles

Preparation method:

(1) measure 70% volume purified water in Agitation Tank.

(2) weighing recipe quantity red algae extract, thimerosal are fed in Agitation Tank, stir and it are all dissolved in 15 minutes.

(3) supply purified water and be settled to full dose.

(4) fill, 10ml/ bottle.

(5) leak detection, packing.

embodiment 2the preparation of Sargassum extract compositions nasal spray

Component	Recipe quantity (g)
		Red algae extract	20g
Thimerosal	0.8g
		Purified water	10000 ml
Make	1000 bottles

Preparation method is with embodiment 1.

embodiment 3the preparation of Sargassum extract compositions nasal spray

Component	Recipe quantity (g)
		Red algae extract	30g
Thimerosal	1.2g
		Purified water	10000 ml
Make	1000 bottles

Preparation method is with embodiment 1.

embodiment 4the preparation of Sargassum extract compositions nasal spray

Component	Recipe quantity (g)
		Red algae extract	6g
Thimerosal	1.0g
		Purified water	10000 ml
Make	1000 bottles

Preparation method is with embodiment 1.

embodiment 5the preparation of Sargassum extract compositions nasal spray

Component	Recipe quantity (g)
		Red algae extract	35g
Thimerosal	1.0g
		Purified water	10000 ml
Make	1000 bottles

Preparation method is with embodiment 1.

embodiment 6the character of nasal spray, pH, minimum fill, every discharge rate inspection

According to the preparation method of embodiment 1, prepare the product of three batches, be respectively 001,002,003 batch, it is carried out to the inspection of character, pH value, loading amount, every discharge rate, the uniformity.

Table 1 check result

Batch	Character	PH value	Loading amount ml	Every discharge rate μ l/ time
					001	Transparent clarification thick liquid	6.60	11.98±0.19	116.3±1.8
002	Transparent clarification thick liquid	7.10	12.01±0.16	108.6±1.4
					003	Transparent clarification thick liquid	7.05	11.98±0.29	112.7±1.6

This nasal spray is clear, colorless liquid, and solution is even, and PH is neutral, and every spray amount is containing principal agent amount homogeneous.

embodiment 7effect experiment

A: get human body nasal cavity epithelial cell, add respectively the red algae extract of variable concentrations and different dilution virus mixture, red algae extract concentrations is respectively 0.5 mg/ml, 0.6 mg/ml, 1.2 mg/ml, 1.5 mg/ml, 2.0mg/ml, 2.5 mg/ml, 3.0mg/ml, 3.5 mg/ml mg/ml, put into 37 ° of C, 5 % CO ₂in cell culture incubator, cultivate.

B: get human body nasal cavity epithelial cell, add the rhinovirus HRV2 of variable concentrations, put into 37 ° of C, 5 % CO ₂in cell culture incubator, infect, add again the red algae extract culture fluid that contains variable concentrations, red algae extract concentrations is respectively 0.5 mg/ml, 0.6 mg/ml, 1.2 mg/ml, 1.5 mg/ml, 2.0mg/ml, 2.5 mg/ml, 3.0mg/ml, 3.5 mg/ml, cell is being put into 37 ° of C, 5 % CO ₂in cell culture incubator, cultivate.

Examine under a microscope CPE, by Reed-Muench Liang Shi method, calculate lgTCID ₅₀value, determines the variation of viral degree.With matched group comparison, result shows that dependency changes and is mainly manifested in following several respects:

1) in experiment a, along with red seaweed polysaccharide extract concentrations increases, virus titer reduces gradually, becomes concentration dependent.

2) in experiment b, along with the increase of red seaweed polysaccharide extract concentrations, virus titer changes without significance.

Experimental result shows, red algae extract solution and viral HRV2 mixing postoperative infection cell are compared virus titer and reduced gradually with the increase of red algae extract solution concentration with matched group, illustrates that red algae extract becomes the inhibitory action of concentration dependent to rhinovirus HRV2.And after cell infection HRV2, when adding variable concentrations red algae extract solution, virus titer all changes without significant compared with the control.Visible, before virus and cells contacting, to suppress viral effect obvious for red algae extract, and the effect of red algae extract unrestraint virus after virus and cells contacting, or act on not obvious.Explanation, red algae extract has the effect of absorption and parcel to virus, can stop the cells contacting of virus and nasal cavity epithelium, prevents the generation of viral infection, but red algae extract, without antiviral effect, can not suppress the virus activity after contacting with nasal cavity epithelial cell.Red algae extract is not killed rhinovirus, affects the effect of rhinovirus replication, can not be subject to the in the situation that nose infecting cell to treat and repair at cell, is merely able to play the effect that prevention rhinovirus is invaded human body.

embodiment 8 stability contrast experiments

Test is to looking like: the red algae extract nasal spray (red algae extract+water) that does not add antibacterial that A red algae extract of the present invention nasal spray (red algae extract+thimerosal+water), B Sargassum nasal spray (Sargassum extract+wetting agent+osmotic pressure regulator+water), C are prepared by the inventive method

Above-mentioned sample is put in the calorstat that 40 ℃ ± 2 ℃ of temperature, relative humidity are 75% ± 5% and placed 7 days, in 7 days last sampling and measuring.Result is as follows:

investigate result

。Note: outward appearance: solution is answered clear, without visible particle; Spray volume: press straightening shower nozzle 20 times, spray volume scope should be 0.8 ~ 1.2ml; Microbial limit: in every 1g this product, bacterial population must not be crossed 100cfu; Fungi count and yeast count must not be crossed 10cfu; Staphylococcus aureus, Pseudomonas aeruginosa must not detect; Escherichia coli must not detect.

Result shows: sample of the present invention is under simulation listing terms of packing, in 40 ℃ ± 2 ℃ of temperature, relative humidity, be under 75% ± 5% condition, to preserve 7 days, every investigation index is good without significant change quality stability, and solution microorganism in accelerated test of B group Sargassum extract+wetting agent+osmotic pressure regulator+water increases; And C group does not add the against regulation and solution of the microbial limit of group of thimerosal and occurs micro-Huang, there is Asian TV Station's granule to occur, quality is unstable, easily produces microorganism; Therefore nasal spray of the present invention is compared with the nasal spray of other groups, quality stability is good.

embodiment 9 drug effect contrast experiments

Experimental subject: red algae extract, E green algal extract that the red algae extract nasal spray (red algae extract+water) of the not adding preservative agent that the red algae extractive composition nasal spray of the present invention (red algae extract+thimerosal+water) of A variable concentrations, B Sargassum nasal spray (Sargassum extract+wetting agent+osmotic pressure regulator+water), C are prepared by the inventive method, D1.2 mg/ml carrageenan, E, mg/ml sulfated polysaccharide group, F brown alga extract replace in A group replace the red algae extract in A group

Get human body nasal cavity epithelial cell, add respectively the red algae extract of variable concentrations and different dilution viral HRV2 mixture, red algae extract concentrations respectively 0.5 mg/ml, 0.6 mg/ml, 1.2 mg/ml, 1.5 mg/ml, 2.0mg/ml, 2.5 mg/ml, 3.0mg/ml, the contained red seaweed polysaccharide of 3.5 mg/ml mg/ml(is 1.27 ~ 2.55mg/ml mg/ml), and other groups, put into 37 ° of C, 5 % CO ₂in cell culture incubator, cultivate.Examine under a microscope CPE, by Reed-Muench Liang Shi method, calculate lgTCID ₅₀value

Equally, by B, C group and different dilution virus mixture, put into 37 ° of C, 5 % CO respectively ₂in cell culture incubator, cultivate.

Cell is used above each mixture solution co-cultivation, measures lgTCID ₅₀the absolute value of value is as shown in the table.

lgTCID under red algae extract variable concentrations ₅₀ absolute value

	1	2	3	4	5	6	Average	SD
									kb	5.33	5.36	5.33	5.33	5.43	5.10	5.31	0.11
0.5 mg/ml	5.42	5.45	5.42	5.42	5.52	5.19	5.40	0.12
									0.6 mg/ml	3.36	3.39	3.36	3.36	3.46	3.13	3.33	0.11
1.2mg/ml	3.44	3.73	3.67	3.49	3.65	3.68	3.60	0.12
									1.5 mg/ml	1.57	1.98	1.90	1.97	1.86	1.90	1.86	0.16
2.0mg/ml	1.33	1.62	1.57	1.38	1.54	1.57	1.50	0.12
									2.5mg/ml	1.07	1.01	1.30	1.01	1.30	1.2	1.16	0.16
3.0mg/ml	1.03	1.01	1.05	1.10	1.07	1.03	1.04	0.15
									3.5mg/ml	1.01	1.02	1.0	1.88	2.14	2.25	2.11	0.16
B group	2.76	2.01	2.98	2.81	2.98	2.97	2.75	0.14
									C group	4.56	4.84	4.78	4.60	4.76	4.79	4.72	0.13
F group	4.78	4.03	4.87	4.81	4.75	4.64	4.64	0.14
									E group	5.23	5.54	5.36	5.42	5.33	5.27	5.35	0.13
Carrageenan group	4.76	4.93	4.88	4.79	4.85	4.88	4.85	0.12
									Sulfated polysaccharide group	4.83	4.12	4.87	4.88	4.04	4.87	4.59	0.13

From the common exposing cell experimental result of red seaweed polysaccharide extract and virus, under the condition that red seaweed polysaccharide extract exists, HRV2 type rhinovirus significantly reduces the epithelial infection ability of human nasal, when red algae extract concentrations is less than 0.6 mg/ml(wherein the amount of red seaweed polysaccharide is less than 0.51mg/ml), successful declines; Preferred concentration range be 1.5 mg/ml ~ 3.5mg/ml(wherein the amount of red seaweed polysaccharide be 1.27 ~ 2.55mg/ml), this inhibitory action is concentration dependent.Therefore red seaweed polysaccharide content is all greater than 0.51mg/ml in red algae extract nasal spray of the present invention, the amount that provides barrier to resist polysaccharide contained in the outside material base red seaweed polysaccharide extract infecting is provided, guaranteed the action effect of this nasal spray.When the content of red seaweed polysaccharide is less than 0.51mg/ml, its effect reduces greatly.And formula of the present invention, compares and does not add the C group of thimerosal and Sargassum extract as the B group of raw material, and activity will be got well; Below also can find out, the D that the single component carrageenan that phase specific concentration is 1.2mg/ml, sulfated polysaccharide are raw material, E group, the nasal spray effect that is raw material with the red algae extract of concentration will be got well; Same red algae extract effect of the present invention will obviously be better than Brown algae, the green algal extract with F, E group; Contrast, therefore employing red algae extract of the present invention is that raw material can be effective more fast and effectively aspect physical protection, has no side effect.

embodiment 10the impact of different dosage forms on drug effect

According to the recipe quantity of the Sargassum extract compositions of embodiment, according to the conventional method of preparing nasal spray, nasal drop, tablet and injection type, prepare these several dosage forms of Sargassum extract compositions; By 50 experimenters, be divided at random 5 groups, experimenter has the symptoms such as nasal cavity that flu in various degree causes is dryly itched, watery nasal discharge, nasal obstruction, sneeze, and wherein one group is blank, uses respectively above four kinds of different dosage forms for all the other four groups; Observe that the nasal cavity of the flu patient in 3 days is dryly itched, watery nasal discharge, nasal obstruction, sneeze improve or healing state.

Result shows: use the transference cures such as 80% patient's the nasal cavity of nasal spray is dryly itched, watery nasal discharge, nasal obstruction, sneeze, flu is cured, and the symptoms such as 18% patient's nasal cavity is dry itches, watery nasal discharge, nasal obstruction, sneeze are obviously improved;

Its cold symptoms of 50% patient of using nasal drop disappears; Patient's cold symptoms of 30% is improved;

Its cold symptoms of 30% patient of using tablet disappears; Patient's cold symptoms of 20% is improved; All the other compare blank group without significant change;

Disappear patient's cold symptoms of 30% of its cold symptoms of 20% patient of using injection type is improved; All the other compare blank group without significant change;

Therefore, Sargassum algae extractive composition is at auxiliary treatment and preventing cold, improves the symptom aspects such as nasal cavity that flu causes is dryly itched, watery nasal discharge, nasal obstruction, sneeze, halitosis, is preferably nasal spray dosage form.

embodiment 11the contrast of various aseptic process modes

Adopt high temperature sterilize, gaseous sterilization, sterilization by ionizing radiation and add the sterilization methods such as antibacterial thimerosal to process Sargassum extract compositions nasal spray, detect the pH value with the nasal spray after upper type sterilizing, result is as follows:

Aseptic process mode	High temperature sterilize	Gaseous sterilization	Sterilization by ionizing radiation	Thimerosal
					During beginning	6.3	6.5	7.0	6.6
After sterilizing	8.5	8.9	8.5	6.6

Upper table is visible, adopt the pH value of the Sargassum extract compositions nasal spray after high temperature sterilize, gaseous sterilization, sterilization by ionizing radiation all to change, not in the scope of normal physiological tolerance, the quality of the pharmaceutical preparations declines, stability is affected, and content is almost unchanged after employing antibacterial, therefore the aseptic process mode that Sargassum extract compositions nasal spray of the present invention adopts is for adding antibacterial.

embodiment 12antibacterial kind is investigated

According to nasal membrane, can tolerate pH value is 6～8, and the feature of red algae extract self preferably efficient, low toxicity, non-irritating antibacterial.The pH value of general snotter is neutral slant acidity, and antibacterial benzoic acid and its esters pH value are 2.5～4.0, sorbic acid and its esters pH value are 3～6, and above two kinds of antibacterial are not paid attention to.Parabens antibacterial is that parabens has certain toxicity, will not add.So in test, main investigation glycerol, benzalkonium bromide, benzoic acid, sorbic acid, potassium sorbate, thimerosal etc., investigation add antibacterial front and back pH value and change, and add solution state after antibacterial, be prepared into auxiliary antiviral lgTCID after same concentration Sargassum extract compositions nasal spray ₅₀the projects such as absolute value, result of the test is as follows:

antiseptic kind is investigated result table

As seen from the experiment, glycerol is done in antibacterial dosing process, has red algae extract to separate out, relevant with dosing order, and after adding glycerol to do antibacterial, pH value changes more obvious.After benzalkonium bromide adds, at once produce white floccule, suspect with red algae extract and react.Benzoic acid adds rear solution to be acid, irritant to nasal mucosa.Sorbic acid dissolubility in water is slightly soluble, can not reach due fungistatic effect.Potassium sorbate adds rear pH value to change obviously, and sample is unstable.Thimerosal is done antibacterial and is added rear pH value variation not obvious, and sample is more stable.And according to the antiviral synergism test after adding, thimerosal is remarkably productive.

To sum up, from dosing sample stability, reach due fungistatic effect, synergistic corrosion virus effect aspect and consider, select thimerosal as antibacterial.

embodiment 13the study on the stability of Sargassum extract nasal spray

Accelerated test: by a collection of simulation listing packing sample, place 7 days in the calorstat that to put 40 ℃ ± 2 ℃ of temperature, relative humidity be 75% ± 5%, in 0,7 day last sampling and measuring.Accelerated test result shows: this product is under simulation listing terms of packing, in 40 ℃ ± 2 ℃ of temperature, relative humidity, be under 75% ± 5% condition, to preserve 7 days, the nasal spray outward appearance of sample, conveyer device outward appearance, pH value, spray volume, assay, the main index of investigating such as microbial limit was compared without significant change with 0 day, steady quality, result is as follows:

accelerated test is investigated result

Long term test: by a collection of simulation listing packing sample, be placed in the chamber that keeps sample (25 ± 2 ℃ of temperature, relative humidity 60% ± 10%), in 3,6,9,12,18,24,30 the end of month sampling and measuring, and compare with the testing result of 0 month.Completed at present the long-term stable experiment of 30 months by a definite date.Long-term test results shows: this product is placed 30 months under the holding conditions of regulation, the main index of investigating such as the nasal spray outward appearance of sample, conveyer device outward appearance, pH value, spray volume, assay, microbial limit was compared without significant change with 0 day, steady quality, result is as follows:

long term test is investigated result

Note: spray volume: press straightening shower nozzle 20 times, spray volume scope should be 0.8 ~ 1.2ml; Microbial limit: in every 1g this product, bacterial population must not be crossed 100cfu; Fungi count and yeast count must not be crossed 10cfu; Staphylococcus aureus, Pseudomonas aeruginosa must not detect; Escherichia coli must not detect.

Can detection by quantitative in red algae extract composition be Sargassum polysaccharides, the present invention relates to red seaweed polysaccharide content in product and be all more than or equal to 0.51mg/ml.

Self-control sample is through accelerating and long term test, the main index of investigating such as the nasal spray outward appearance of sample, conveyer device outward appearance, pH value, spray volume, assay, microbial limit was compared without significant change with 0 month, illustrate that product formulation and technology of the present invention is simple, easy to operate, good stability.

Although the present invention elaborates it by above-mentioned specific embodiment; but; those skilled in the art should be understood that any form that does not exceed claim protection domain made on this basis and the variation of details, all belong to invention which is intended to be protected.

Claims (9)

1. a novel alga extractive composition, it consists of red algae extract, antibacterial and purified water; Wherein red algae extract concentrations is 0.6 ~ 3.5 mg/mL, and antibacterial concentration is 0.08 ~ 0.12mg/mL.

2. novel alga extractive composition according to claim 1, is characterized in that: described red algae extract concentrations is 1. 5 ~ 3.0 mg/mL.

3. novel alga extractive composition according to claim 1 and 2, is characterized in that: the dosage form of described compositions is nasal spray.

4. according to the arbitrary described novel alga extractive composition of claims 1 to 3, it is characterized in that: described antibacterial is selected from one or more in glycerol, benzalkonium bromide, benzoic acid, sorbic acid, potassium sorbate, thimerosal.

5. novel alga extractive composition according to claim 4, is characterized in that: described antibacterial is thimerosal.

6. according to the arbitrary described novel alga extractive composition of claim 1 to 5, it is characterized in that: described compositions pH value scope is 6.0 ~ 7.0.

7. a preparation method for the nasal spray of novel alga extractive composition claimed in claim 3, preparation process is as follows:

Measure 70% volume purified water in Agitation Tank; Weighing recipe quantity red algae extract, antibacterial are fed in Agitation Tank, stir it is all dissolved; Supply purified water and be settled to full dose; Fill, 10ml/ bottle; Leak detection, packing.

8. the preparation method of the nasal spray of novel alga extractive composition according to claim 7, is characterized in that: described antibacterial is thimerosal.

9. a novel alga extractive composition claimed in claim 1, maintaining that nasal mucosa is moistening, aspect preventing cold, improves that nasal cavity that flu causes is dryly itched, the application of watery nasal discharge, nasal obstruction, sneeze, halitosis symptom aspect.