Formula and preparation method of traditional Chinese medicine eye-protecting eye drops

Abstract

The invention relates to the technical field of traditional Chinese medicine eye-protecting eye drops, in particular to a traditional Chinese medicine eye-protecting eye drop formula and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine preparations. The eye drops are composed of carbomer, glycerin, xanthophyll and 25 traditional Chinese medicine extracts, solubility is improved through a grouping dissolution process, and sterility is guaranteed through three-stage filtration and hot-pressing sterilization. The preparation method comprises the following steps: preparing the carbomer gel matrix, premixing glycerol and xanthophyll, redissolving the traditional Chinese medicine extract, adjusting the pH value of the main liquid medicine to 6.5-7.5, storing in a dark place under nitrogen charging and the like. The pH value of the product is 7.0 + / -0.2, the viscosity is 15-25 mPa.s, the osmotic pressure is 280-320 mOsm / kg, and the stability reaches 24 months. The problems that traditional Chinese medicine eye drops are prone to precipitation, the process is unstable and microbial contamination is caused are solved, and the eye drops are suitable for relieving eyestrain, xerophthalmia and eye inflammation and have the advantages of being natural, mild and small in side effect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine eye-protecting eye drops, in particular to a traditional Chinese medicine eye-protecting eye drop formula and a preparation method. BACKGROUND

[0002] With the popularity of electronic devices, the incidence of eye diseases such as eye fatigue, dry eye, conjunctivitis, etc. is increasing year by year. The existing eye drops are mainly chemical synthetic drugs, which are easy to produce drug resistance and side effects after long-term use. Traditional Chinese medicine eye drops are gradually attracting attention due to their natural, mild and small side effects. However, the existing traditional Chinese medicine eye drops have the following problems:

[0003] (1) Poor solubility of traditional Chinese medicine extract, easy to precipitate;

[0004] (2) Poor process stability, large batch difference;

[0005] (3) Incomplete sterilization measures, easy to breed microorganisms. SUMMARY

[0006] The purpose of the present application is to provide a traditional Chinese medicine eye-protecting eye drop formula and a preparation method to solve the problems raised in the background art and facilitate popularization.

[0007] In order to achieve the above-mentioned purpose of the application, the technical scheme adopted by the present application is:

[0008] A traditional Chinese medicine eye-protecting eye drop formula is prepared from the following raw materials by weight:

[0009] 0.1-1.0 parts of carbomer, 1.0-3.0 parts of glycerol, 0.01-0.05 parts of lutein, 10-30 parts of traditional Chinese medicine extract group, and purified water added to 100 parts;

[0010] The traditional Chinese medicine extract group is prepared from the following traditional Chinese medicinal materials by extraction:

[0011] 1-3 parts of Cassia seed, 1-3 parts of Lotus leaf, 1-3 parts of Poria cocos, 1-3 parts of Honeysuckle, 1-3 parts of Gypsophila oldhamiana, 1-3 parts of Dodder, 1-3 parts of Rehmannia glutinosa, 1-3 parts of Radix Rehmanniae Praeparatae, 1-3 parts of Dendrobium, 1-3 parts of Prunella vulgaris, 1-3 parts of Chrysanthemum, 1-3 parts of Houttuynia cordata, 1-3 parts of Green tea, 1-3 parts of Licorice, 1-3 parts of Wormwood, 1-3 parts of Angelica sinensis, 1-3 parts of Salvia miltiorrhiza, 1-3 parts of Apricot kernel, 1-3 parts of Mulberry leaf, 1-3 parts of Jussiaea stipulacea, 1-3 parts of Gentiana scabra, 1-3 parts of Ophiopogon japonicus, 1-3 parts of Carthamus tinctorius, 1-3 parts of Chuanxiong, 1-3 parts of Schisandra chinensis.

[0012] Further, the weight fraction of carbomer is 0.5 parts, the weight fraction of glycerol is 2.0 parts, the weight fraction of lutein is 0.02 parts, and the weight fraction of traditional Chinese medicine extract group is 20 parts.

[0013] A preparation method of a traditional Chinese medicine eye-protecting eye drop, comprising the following steps:

[0014] Step (1): Carbomer gel base preparation: uniformly spread carbomer in purified water, stand for swelling for 12-24 hours, stir at a temperature of 20-30 DEG C and a rotating speed of 100-300 rpm until completely dissolved, and stand for use after cooling to room temperature;

[0015] Step (2): Glycerol-xanthophyll premix preparation: mix glycerol and xanthophyll, stir at a temperature of 40-60 DEG C and a rotating speed of 200-400 rpm until completely dissolved, and stand for use after cooling to room temperature;

[0016] Step (3): Traditional Chinese medicine extract re-dissolution: divide the traditional Chinese medicine extract into water-soluble and alcohol-soluble groups, extract the water-soluble group with 10 times amount of purified water at a temperature of 80-90 DEG C for 2 times, each for 1 hour, combine the filtrates; extract the alcohol-soluble group with 5 times amount of 30% ethanol at a temperature of 60-70 DEG C for 3 times, each for 0.5 hour, combine the filtrates; filter the water-soluble group and the alcohol-soluble group through 0.45 mu m microporous filter membranes respectively, and combine and concentrate to a relative density of 1.05-1.10;

[0017] Step (4): Main liquid preparation: mix the carbomer gel base, the glycerol-xanthophyll premix and the traditional Chinese medicine extract re-dissolution, add purified water to constant volume, adjust pH to 6.5-7.5 with a pH regulator, and stir at a temperature of 20-30 DEG C and a rotating speed of 100-300 rpm until uniform;

[0018] Step (5): Terminal sterilization and filling: sequentially filter the main liquid through 0.45 mu m, 0.22 mu m and 0.10 mu m microporous filter membranes in three stages, and fill into sterile eye drop bottles under sterile conditions, and adopt 121 DEG C hot pressure sterilization for 15 minutes.

[0019] Further, the swelling time of carbomer in step (1) is 18 hours, and the stirring rotating speed is 200 rpm; the stirring temperature of glycerol and xanthophyll in step (2) is 50 DEG C, and the rotating speed is 300 rpm; and the pH regulator in step (4) is boric acid-borax buffer.

[0020] Further, the water-soluble group in step (3) comprises cassia seed, lotus leaf, poria cocos, honeysuckle, mexican prairie, radix rehmanniae, radix rehmanniae praeparata, dendrobium, prunella vulgaris, chrysanthemum, houttuynia cordata, green tea, licorice, wormwood, angelica, salvia miltiorrhiza, apricot kernel, mulberry leaf, paper mulberry, gentiana scabra, ophiopogon, safflower, chuanxiong, schisandra chinensis; and the alcohol-soluble group comprises cuscuta chinensis, cuscuta chinensis, cuscuta chinensis.

[0021] 6. The preparation method of the traditional Chinese medicine eye-protecting eye drops according to any one of claims 3 to 5, characterized in that the filter membrane pore size of the three-stage filtration in the step (5) is 0.45 μm, 0.22 μm and 0.10 μm in sequence, the filtration pressure is 0.1-0.3 MPa, and the filtration flow rate is 10-30 mL / min.

[0022] Further, the pH value of the eye drops is 7.0±0.2, the viscosity is 15-25 mPa·s, the osmotic pressure is 280-320 mOsm / kg, and the bubble point of the bacterial filtration integrity is ≥0.33 MPa.

[0023] Further, the eye drops are prepared by adopting nitrogen protection, the eye drop bottles are made of amber LDPE material, and the eye drops are stored in the dark during storage.

[0024] As an improvement, the beneficial effects of the present application are:

[0025] 1. Traditional Chinese medicine extract grouping dissolution process: The traditional Chinese medicine extract is divided into water-soluble group and alcohol-soluble group, and is combined after being extracted respectively, so as to avoid the interaction between the extracts and improve the solubility and stability.

[0026] 2. Three-stage filtration sterilization technology: 0.45 μm, 0.22 μm and 0.10 μm microporous filter membranes are used for three-stage filtration, combined with heat sterilization, so as to ensure that the aseptic assurance level reaches SAL 10-3.

[0027] 3. Stability guarantee system: nitrogen protection, light storage, preservative challenge test and other measures are adopted to ensure the long-term stability of the product, and the effective period reaches 24 months. DETAILED DESCRIPTION

[0028] In order to make the content of the present application more easily understood, the technical solutions in the embodiments of the present application will be clearly and completely described below in combination with the embodiments of the present application.

[0029] Example 1 (small-scale test)

[0030] Formulation composition (per 100 mL):

[0031] Carbomer 0.5 g, glycerol 2.0 g, lutein 0.02 g, traditional Chinese medicine extract group 2.0 g (containing 25 kinds of traditional Chinese medicines such as cassia seed, each 0.08 g), purified water added to 100 mL.

[0032] Preparation process:

[0033] 1. Preparation of carbomer gel matrix:

[0034] 0.5 g of carbomer is uniformly spread in 90 mL of purified water, and is left to swell for 18 hours.

[0035] Stir at 25℃, 200 rpm until completely dissolved, and cool to room temperature. Stand by for use.

[0036] 2. Preparation of glycerol-xanthophyll premix:

[0037] Mix 2.0 g of glycerol with 0.02 g of xanthophyll, and stir at 50℃, 300 rpm until completely dissolved.

[0038] Cool to room temperature. Stand by for use.

[0039] 3. Reconstitution of traditional Chinese medicine extract:

[0040] Water-soluble group (16 flavors): Cassia, Lotus Leaf, Poria cocos, honeysuckle, Mi Menghua, Rehmannia glutinosa, Radix Rehmanniae Recens, Dendrobium, Prunella vulgaris, Chrysanthemum, Houttuynia cordata, green tea, licorice, wormwood, angelica, salvia miltiorrhiza, 0.08 g each, 10 times the amount of purified water was extracted at 85℃ for 2 times, 1 hour each time, and the filtrate was combined.

[0041] Alcohol-soluble group (9 flavors): Semen cuscutae, Semen cuscutae, Semen cuscutae (Note: The original text is repeated, and it should actually be Semen cuscutae, Prunus armeniaca, mulberry leaf, Fructus Engelhardtiae, gentiana, Ophiopogon japonicus, safflower, chuanxiong, Schisandra chinensis), 0.08 g each, 5 times the amount of 30% ethanol was extracted at 65℃ for 3 times, 0.5 hour each time, and the filtrate was combined.

[0042] The filtrate of the water-soluble group and the alcohol-soluble group was filtered through a 0.45 μm microporous filter membrane, and then concentrated to a relative density of 1.08 after being combined.

[0043] 4. Preparation of main drug solution:

[0044] Mix carbomer gel matrix, glycerol-xanthophyll premix, and reconstituted traditional Chinese medicine extract solution, and add purified water to make up to 100 mL.

[0045] Adjust the pH to 7.0 with boric acid-borax buffer, and stir at 25℃, 200 rpm until uniform.

[0046] 5. Terminal sterilization and filling:

[0047] The main drug solution was sequentially filtered through a 0.45 μm, 0.22 μm, and 0.10 μm microporous filter membrane, with a filtration pressure of 0.2 MPa and a flow rate of 20 mL / min.

[0048] Under sterile conditions, fill into amber LDPE eye drop bottles, 10 mL per bottle, and use 121℃ hot pressure sterilization for 15 minutes.

[0049] Quality control:

[0050] pH: 7.0 ± 0.2

[0051] Viscosity: 20 mPa-s

[0052] Osmotic pressure: 300 mOsm / kg

[0053] Sterile filtration integrity: bubble point 0.35 MPa

[0054] Sterility test: membrane filtration method incubated for 14 days, no microbial growth

[0055] Content determination: HPLC method for determining lutein content of 0.02 g / 100 mL.

[0056] Example 2 (scale-up production, 1000 L scale)

[0057] Formulation composition (per 1000 L):

[0058] Carbomer 0.5 kg, glycerol 2.0 kg, lutein 0.02 kg, traditional Chinese medicine extract group 20 kg (containing 25 kinds of traditional Chinese medicines such as Cassia seed, 0.8 kg each), purified water to 1000 L.

[0059] Preparation process:

[0060] 1. Preparation of carbomer gel base:

[0061] 0.5 kg of carbomer was evenly spread in 900 L of purified water and allowed to swell for 24 hours.

[0062] Stir at 25°C, 200 rpm until completely dissolved, and cool to room temperature for standby.

[0063] 2. Preparation of glycerol-lutein premix:

[0064] Mix 2.0 kg of glycerol with 0.02 kg of lutein, stir at 50°C, 300 rpm until completely dissolved.

[0065] Cool to room temperature for standby.

[0066] 3. Resuspension of traditional Chinese medicine extract:

[0067] Water-soluble group (16 kinds): Take 0.8 kg of each, extract with 10 times the amount of purified water at 85°C for 2 times, 1 hour each time, and combine the filtrate.

[0068] Alcohol-soluble group (9 kinds): Take 0.8 kg of each, extract with 5 times the amount of 30% ethanol at 65°C for 3 times, 0.5 hours each time, and combine the filtrate.

[0069] The filtrate of the water-soluble group and the alcohol-soluble group is filtered through a 0.45 μm microporous filter, and then concentrated to a relative density of 1.08 after being combined.

[0070] 4. Preparation of main liquid:

[0071] Mix the carbomer gel matrix, glycerol-xanthophyll premix solution and the Chinese medicine extract reconstitution solution, and add purified water to make up to 1000L.

[0072] Adjust the pH to 7.0 with boric acid-borax buffer, and stir at 25℃ and 200rpm until uniform.

[0073] 5. Terminal sterilization and filling:

[0074] The main liquid sequentially passes through three levels of filtration of 0.45μm, 0.22μm and 0.10μm microporous filter membranes, with a filtration pressure of 0.2MPa and a flow rate of 20L / min.

[0075] Under sterile conditions, fill into amber LDPE eye drop bottles, 10mL per bottle, and use 121℃ hot pressure sterilization for 15 minutes.

[0076] Quality control:

[0077] pH value: 7.0±0.2

[0078] Viscosity: 22mPa·s

[0079] Osmotic pressure: 310mOsm / kg

[0080] Sterilization filtration integrity: bubble point 0.36MPa

[0081] Sterile detection: membrane filtration method for 14 days, no microbial growth

[0082] Content determination: HPLC method for determining xanthophyll content of 0.02kg / 1000L.

[0083] The above is only a preferred embodiment of the patent, and does not limit the patent, any modification, equivalent replacement and improvement within the spirit and principle of the patent should be included in the protection scope of the patent.

Claims

1. A traditional Chinese medicine eye drop formula, characterized in that, Made from the following parts by weight of raw materials: Carbomer 0.1–1.0 parts, glycerin 1.0–3.0 parts, lutein 0.01–0.05 parts, Chinese herbal extract group 10–30 parts, purified water added to 100 parts; The herbal extract group is obtained by extraction from the following herbal materials in parts by weight: Cassia seed 1-3 parts, lotus leaf 1-3 parts, Poria cocos 1-3 parts, honeysuckle 1-3 parts, buddleja officinalis 1-3 parts, dodder seed 1-3 parts, raw rehmannia root 1-3 parts, prepared rehmannia root 1-3 parts, dendrobium 1-3 parts, prunella vulgaris 1-3 parts, chrysanthemum 1-3 parts, houttuynia cordata 1-3 parts, green tea 1-3 parts, licorice root 1-3 parts, mugwort leaf 1-3 parts, angelica sinensis 1-3 parts, salvia miltiorrhiza 1-3 parts, apricot kernel 1-3 parts, mulberry leaf 1-3 parts, paper mulberry fruit 1-3 parts, gentian root 1-3 parts, ophiopogon japonicus 1-3 parts, safflower 1-3 parts, chuanxiong rhizome 1-3 parts, schisandra fruit 1-3 parts.

2. The formula for a traditional Chinese medicine eye drop according to claim 1, characterized in that, The carbomer is 0.5 parts by weight, glycerin is 2.0 parts by weight, lutein is 0.02 parts by weight, and the herbal extract group is 20 parts by weight.

3. A method for preparing a traditional Chinese medicine eye drop, characterized in that, Includes the following steps: Step (1): Carbomer gel matrix preparation: Carbomer is evenly sprinkled in purified water and allowed to stand for swelling for 12-24 hours. It is stirred at 20-30℃ and 100-300rpm until completely dissolved. After cooling to room temperature, it is allowed to stand for later use. Step (2): Preparation of glycerol-lutein premix: Mix glycerol and lutein, stir at 40-60℃ and 200-400rpm until completely dissolved, cool to room temperature and let stand for later use; Step (3): Reconstitution of Chinese herbal extracts: The Chinese herbal extracts were divided into water-soluble group and alcohol-soluble group. The water-soluble group was extracted twice with 10 times the amount of purified water at a temperature of 80-90℃ for 1 hour each time, and the filtrates were combined. The alcohol-soluble group was extracted three times with 5 times the amount of 30% ethanol at a temperature of 60-70℃ for 0.5 hours each time, and the filtrates were combined. The filtrates of the water-soluble group and the alcohol-soluble group were filtered through a 0.45μm microporous membrane, and the combined filtrates were concentrated to a relative density of 1.05-1.

10. Step (4): Preparation of main drug solution: Mix carbomer gel matrix, glycerol-lutein premix and traditional Chinese medicine extract complex solution, add purified water to make up to the total volume, adjust pH to 6.5-7.5 with pH adjuster, and stir until uniform at 20-30℃ and 100-300rpm. Step (5): Terminal sterilization and filling: The main drug solution is filtered through three stages of 0.45μm, 0.22μm and 0.10μm microporous membranes in sequence, and then filled into sterile eye drop bottles under aseptic conditions. The solution is then autoclaved at 121℃ for 15 minutes.

4. The method for preparing a traditional Chinese medicine eye drop according to claim 3, characterized in that, In step (1), the swelling time of carbomer is 18 hours and the stirring speed is 200 rpm. In step (2), the stirring temperature of glycerol and lutein is 50℃ and the stirring speed is 300 rpm. In step (4), the pH adjuster is boric acid-borax buffer solution.

5. The preparation method of a traditional Chinese medicine eye drop according to claim 4, characterized in that, In step (3), the water-soluble group includes cassia seed, lotus leaf, poria cocos, honeysuckle, buddleja officinalis, rehmannia glutinosa (raw and processed), dendrobium, prunella vulgaris, chrysanthemum, houttuynia cordata, green tea, licorice, mugwort leaf, angelica sinensis, salvia miltiorrhiza, apricot kernel, mulberry leaf, paper mulberry fruit, gentian, ophiopogon japonicus, safflower, chuanxiong rhizome, and schisandra chinensis; the alcohol-soluble group includes dodder seed, dodder seed, and dodder seed.

6. A method for preparing a traditional Chinese medicine eye drop according to any one of claims 3 to 5, characterized in that, In step (5), the pore sizes of the three-stage filtration membranes are 0.45μm, 0.22μm, and 0.10μm, respectively, the filtration pressure is 0.1-0.3MPa, and the filtration flow rate is 10-30mL / min.

7. A traditional Chinese medicine eye drop according to any one of claims 1 to 6, characterized in that, The eye drops have a pH of 7.0±0.2, a viscosity of 15-25 mPa·s, an osmotic pressure of 280-320 mOsm / kg, and a foaming point ≥0.33 MPa for sterilization and filtration integrity.

8. A traditional Chinese medicine eye drop according to any one of claims 1 to 7, characterized in that, The eye drops are prepared using nitrogen purging for protection, and the eye drop bottle is made of amber-colored LDPE material. It is also stored away from light during storage.