CN112194574B - Preparation method of o-vanillin spherical crystal - Google Patents
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- JJVNINGBHGBWJH-UHFFFAOYSA-N ortho-vanillin Chemical compound COC1=CC=CC(C=O)=C1O JJVNINGBHGBWJH-UHFFFAOYSA-N 0.000 title claims abstract description 67
- 239000013078 crystal Substances 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 41
- 238000003756 stirring Methods 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 25
- 239000004094 surface-active agent Substances 0.000 claims abstract description 16
- 239000011259 mixed solution Substances 0.000 claims abstract description 15
- 239000000243 solution Substances 0.000 claims abstract description 13
- 239000007791 liquid phase Substances 0.000 claims abstract description 8
- 238000005191 phase separation Methods 0.000 claims abstract description 8
- 238000001816 cooling Methods 0.000 claims description 17
- 238000001035 drying Methods 0.000 claims description 11
- 238000005406 washing Methods 0.000 claims description 11
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 5
- 239000007900 aqueous suspension Substances 0.000 claims description 3
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 claims description 3
- 235000019982 sodium hexametaphosphate Nutrition 0.000 claims description 3
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical group [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 claims description 3
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 1
- 239000002245 particle Substances 0.000 abstract description 18
- 239000002994 raw material Substances 0.000 abstract description 6
- 239000002904 solvent Substances 0.000 abstract description 5
- 238000002425 crystallisation Methods 0.000 abstract description 4
- 230000008025 crystallization Effects 0.000 abstract description 4
- 238000010791 quenching Methods 0.000 abstract 1
- 239000000725 suspension Substances 0.000 abstract 1
- 239000012798 spherical particle Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 7
- 238000002441 X-ray diffraction Methods 0.000 description 6
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- 239000007788 liquid Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 4
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- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004581 coalescence Methods 0.000 description 2
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 description 2
- 238000007440 spherical crystallization Methods 0.000 description 2
- 239000002262 Schiff base Substances 0.000 description 1
- 238000007441 Spherical agglomeration method Methods 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000011549 crystallization solution Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 238000009713 electroplating Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000002831 nitrogen free-radicals Chemical class 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940076372 protein antagonist Drugs 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开一种邻香草醛球形晶体的制备方法。在40～50℃下，配制邻香草醛浓度为0.01～0.20g/mL的邻香草醛‑水混合悬浮液；维持搅拌至溶液发生液液相分离；将溶液骤冷至1～15℃，持续搅拌至出晶；加入质量分数为0.02％～0.40％的表面活性剂(基于邻香草醛‑水混合溶液的质量)，保持搅拌0.5～5h，使晶体聚结成球。过滤、洗涤、干燥，得到邻香草醛球形晶体。所述结晶过程原料单一，溶剂只涉及到水，绿色环保，工艺简单。球晶产品颗粒粒径可通过搅拌速率有效调节，产品的平均粒径300～1200微米左右；晶体颗粒圆润，流动性高，休止角在30°～33°之间，振实密度为0.50～0.58g/cm3。
The invention discloses a preparation method of o-vanillin spherical crystal. At 40-50°C, prepare an o-vanillin-water mixed suspension with a concentration of o-vanillin of 0.01-0.20 g/mL; maintain stirring until the liquid phase separation occurs in the solution; quench the solution to 1-15°C, continue Stir until crystals appear; add 0.02% to 0.40% surfactant (based on the mass of the o-vanillin-water mixed solution), keep stirring for 0.5 to 5 hours, to make the crystals agglomerate into balls. Filter, wash and dry to obtain spherical crystals of o-vanillin. The crystallization process has a single raw material, only water is involved in the solvent, and the process is green and environmentally friendly, and the process is simple. The particle size of spherulite products can be effectively adjusted by the stirring rate. The average particle size of the product is about 300-1200 microns; the crystal particles are round and have high fluidity, the angle of repose is between 30° and 33°, and the tap density is 0.50-0.58 g/cm 3 .
Description
Technical Field
The invention belongs to the technical field of chemical engineering industrial crystallization, and particularly relates to a preparation method of o-vanillin spherical crystals.
Background
O-vanillin (CAS: 148-53-8), chemical name 2-hydroxy-3-methoxybenzaldehyde, alias o-vanillin, 2-vanillin, and the like. The o-vanillin is mainly used as a medical intermediate, is an important starting material for synthesizing various raw material medicines and spices, and is also used in the industries of pharmacy, electroplating and the like. English name ortho-vanillin, molecular formula C8H8O3Molecular weight 152.15, typically a pale yellow crystalline solid with a melting point of 40 ℃ to 42 ℃. Slightly soluble in cold water, and soluble in hot water, ethanol, ether, and acetone. O-vanillin is a fragrance commonly used in the chemical industryThe organic synthesis intermediate has many similar functions to the isomer vanillin. In vitro, o-vanillin can scavenge active oxygen free radicals, active nitrogen free radicals, and has antifungal and antibacterial effects. In recent years, the research shows that the o-vanillin can reduce the polymerization and sickling of red blood cells of patients with sickle cell anemia and reduce the damage of ions of the red blood cells. Because of the anti-inflammatory and antioxidant functions of o-vanillin, o-vanillin is hopeful to be a novel transmembrane protein antagonist and to be an effective medicament for treating sleep apnea.
The type of the preparation has different requirements on the crystal habit and the particle size of the o-vanillin raw material medicine, for example, the o-vanillin raw material medicine for direct tabletting or capsule filling needs a product with larger particle size and good powder performance. However, the o-vanillin crystals are mostly needle-shaped or rod-shaped crystals (as shown in fig. 1), and have low bulk density and poor flowability, which is very disadvantageous for downstream formulation processing operations. In addition, o-vanillin has a strong tendency to agglomerate and agglomerate at slightly higher ambient temperatures, due to its low melting point (40 ℃ to 42 ℃). At present, reports about o-vanillin mainly focus on the synthesis of bis-schiff base and the synthesis of derivatives thereof, but the regulation of crystal morphology thereof is rarely reported. The preparation of spherulites of o-vanillin is the next major research direction because of its high bulk density, high flowability, high stability, high particle uniformity and good coating and tabletting properties. The traditional preparation process of the spherical crystal mainly comprises a spherical agglomeration method and a quasi-emulsion solvent diffusion method, but the method needs to use a plurality of organic solvents to easily cause organic solvent residues on one hand, and has high requirements on solvent system selection and operation condition control due to different physical and chemical properties of different substances on the other hand. Therefore, the preparation of o-vanillin high powder performance spherulites and the development of a novel spherical crystallization technology are necessary.
In summary, the problems in the current production of o-vanillin are: the needle-shaped or rod-shaped crystal product has low bulk density and poor fluidity, and is seriously agglomerated to be not beneficial to downstream processing; the existing spherical crystallization means has high organic solvent residue, complex solvent system selection and difficult process control.
Therefore, the search for a method for preparing o-vanillin, which has high bulk density of crystal particles, good fluidity, difficult agglomeration and simple process flow, is still an unsolved technical problem in the prior art.
Disclosure of Invention
In order to overcome the defects of the existing o-vanillin product, the invention provides a method for preparing o-vanillin spherical crystals by liquid-liquid phase separation, and the prepared spherical o-vanillin crystal product has uniform particles, good dispersibility and good fluidity, and meanwhile, the process is green and environment-friendly.
The technical scheme of the invention is as follows:
a method for preparing o-vanillin spherical crystals, which comprises the following steps:
(1) preparing o-vanillin-water suspension with o-vanillin concentration of 0.01-0.20 g/mL at 40-50 ℃; stirring until liquid-liquid phase separation occurs and oil drops of o-vanillin are dispersed in water;
(2) cooling the solution to 1-15 ℃, and then continuously stirring until crystals are formed; adding a surfactant, and continuously stirring for 0.5-4 h to enable crystals to be aggregated into compact spheres;
(3) filtering, washing and drying to obtain o-vanillin spherical crystals.
The cooling rate in the step (2) is 4-5 ℃/1 min.
The surfactant in the step (2) is selected from one of sodium stearate, sodium hexametaphosphate, sodium dodecyl benzene sulfonate or sodium dodecyl sulfate, and the addition amount of the surfactant is 0.05-0.40% of the mass of the o-vanillin-water mixed solution in the step (1).
The particle size of the spheres in the step (2) can be adjusted by changing the stirring speed: the stirring speed is increased, the size of the formed o-vanillin oil drops is smaller, and a spherical product with small particle size can be obtained correspondingly. For example, for a solution with the volume of 40-80 mL, the stirring speed is kept between 100-300 rpm, and the average grain diameter of the o-vanillin product crystals is about 300-1200 microns. As the volume of the crystallization solution increases, the corresponding stirring rate range should also increase to ensure that the o-vanillin is uniformly dispersed in the water in the form of oil droplets.
The washing in the step (3) is washing with water.
The drying conditions in the step (3) are normal pressure, the temperature is 20-35 ℃, and the drying time is 12-48 h.
The o-vanillin spherical product has round crystal particles, high fluidity, an angle of repose of 30-33 degrees and a tap density of 0.50-0.58 g/cm as shown in figure 23。
The o-vanillin spherical product crystal is in a stable crystal form, and is shown in figure 3.
Due to the low melting point and the low solubility of o-vanillin in water, a liquid-liquid phase separation phenomenon (i.e. a layering phenomenon of liquid o-vanillin and water under a static condition) can occur at 40-50 ℃ in an o-vanillin-water suspension with a concentration of 0.01-0.20 g/mL. O-vanillin is then stably and uniformly dispersed in water in the form of oil droplets by applying an appropriate rate of agitation, providing an oil droplet microenvironment for the crystallization of o-vanillin. Under the condition of rapid cooling, o-vanillin in the oil drops is rapidly crystallized and agglomerated into balls, and a proper amount of surfactant is added to finally obtain a spherical o-vanillin product with compact particles.
In the method, the method has the following beneficial effects:
1. the method effectively creates the spherical oil drop environment for nucleation and growth of o-vanillin, and has simple process and high efficiency.
2. The method ensures that the o-vanillin oil drops are stably and uniformly dispersed in water by adding the surfactant, effectively prevents coalescence among the o-vanillin oil drops, and thus prepares the spherical particles with no coalescence and good fluidity.
3. The spherical product obtained by the method has excellent filling property, compression formability and stability, can be directly tabletted, and greatly reduces the industrial cost.
4. The method only uses water as a solvent in the whole process, has single raw material, is green and environment-friendly, has simple process, can realize industrialization and has low economic investment.
Drawings
FIG. 1: photo of o-vanillin raw material drug (50 μm on scale of 1).
FIG. 2: photographic picture of o-vanillin spherical particles (50 μm on scale of 1).
FIG. 3: o-vanillin spherical particle XRD powder diffraction pattern.
Detailed Description
Example 1:
(1) preparing 60mL of o-vanillin-water mixed solution of 0.01g/mL at 40 ℃, and stirring until liquid-liquid separation occurs and o-vanillin oil drops are uniformly distributed in water;
(2) the solution was cooled to 5 ℃ at a cooling rate of 5 ℃/1min, the stirring rate was maintained at 300rpm until crystallization occurred, and 0.02% of sodium stearate, a surfactant, was added (based on the mass of the o-vanillin-water mixed solution). Continuously stirring for 0.5h to enable the crystals to be agglomerated into compact spheres;
(3) vacuum filtering, washing with water, and drying at 20 deg.C under normal pressure for 12 hr to obtain spherical o-vanillin crystal.
The XRD pattern of the product is shown in figure 1, from which it can be seen that the product is a stable crystal; the average particle size of the spherical particles is 300 microns, the angle of repose is 31 degrees, and the tap density is 0.50g/cm3。
Example 2:
(1) preparing 60mL of o-vanillin-water mixed solution of 0.10g/mL at 45 ℃, and stirring until liquid-liquid separation occurs and o-vanillin oil drops are uniformly distributed in water;
(2) cooling the solution to 2 ℃ at the cooling rate of 4.5 ℃/1min, maintaining the stirring rate of 250rpm until crystal appears, and adding 0.15 percent of sodium hexametaphosphate (based on the mass of the o-vanillin-water mixed solution) serving as a surfactant. Continuously stirring for 2.5h to enable the crystals to be agglomerated into compact spheres;
(3) vacuum filtering, washing with water, and drying at 30 deg.C under normal pressure for 24 hr to obtain spherical o-vanillin crystal.
XRD pattern of the productThe spectrum is shown in FIG. 1, from which it can be seen that the product is a stable crystal; the average particle size of the spherical particles is 500 micrometers, the angle of repose is 31 degrees, and the tap density is 0.58g/cm3。
Example 3:
(1) preparing 60mL of o-vanillin-water mixed solution of 0.15g/mL at 50 ℃, and stirring until liquid-liquid phase separation occurs and o-vanillin oil drops are uniformly distributed in water;
(2) cooling the solution to 10 ℃ at a cooling rate of 4 ℃/1min, maintaining the stirring rate at 200rpm until crystal appears, and adding 0.30 percent of sodium dodecyl benzene sulfonate serving as a surfactant (based on the mass of the o-vanillin-water mixed solution). Continuously stirring for 3h to enable the crystals to be aggregated into compact spheres;
(3) vacuum filtering, washing with water, and drying at 35 deg.C under normal pressure for 36 hr to obtain spherical o-vanillin crystal.
The XRD pattern of the product is shown in figure 1, from which it can be seen that the product is a stable crystal; the average particle size of the spherical particles is 800 micrometers, the angle of repose is 33 degrees, and the tap density is 0.55g/cm3。
Example 4:
(1) preparing 60mL of o-vanillin-water mixed solution of 0.20g/mL at 50 ℃, and stirring until liquid-liquid separation occurs and o-vanillin oil drops are uniformly distributed in water;
(2) cooling the solution to 15 ℃ at a cooling rate of 4 ℃/1min, maintaining the stirring rate at 100rpm until crystal appears, and adding 0.40 percent of surfactant sodium dodecyl sulfate (based on the mass of the o-vanillin-water mixed solution). Continuously stirring for 5h to enable the crystals to be agglomerated into compact spheres;
(3) vacuum filtering, washing with water, and drying at 35 deg.C under normal pressure for 48 hr to obtain spherical o-vanillin crystal.
The XRD pattern of the product is shown in figure 1, from which it can be seen that the product is a stable crystal; the average particle size of the spherical particles was 1200. mu.m, the angle of repose was 30 ℃ and the tap density was 0.53g/cm3。
Example 5:
(1) preparing 40mL of o-vanillin-water mixed solution of 0.20g/mL at 50 ℃, and stirring until liquid-liquid separation occurs and o-vanillin oil drops are uniformly distributed in water;
(2) cooling the solution to 15 ℃ at a cooling rate of 4 ℃/1min, maintaining the stirring speed at 120rpm until crystal appears, and adding 0.40 percent of surfactant sodium dodecyl sulfate (based on the mass of the o-vanillin-water mixed solution). Continuously stirring for 5h to enable the crystals to be agglomerated into compact spheres;
(3) vacuum filtering, washing with water, and drying at 35 deg.C under normal pressure for 48 hr to obtain spherical o-vanillin crystal.
The XRD pattern of the product is shown in figure 1, from which it can be seen that the product is a stable crystal; the average particle size of the spherical particles is 1000 microns, the angle of repose is 32 degrees, and the tap density is 0.50g/cm3。
Example 6:
(1) preparing 80mL of o-vanillin-water mixed solution of 0.20g/mL at 50 ℃, and stirring until liquid-liquid phase separation occurs and o-vanillin oil drops are uniformly distributed in water;
(2) cooling the solution to 15 ℃ at a cooling rate of 4 ℃/1min, maintaining the stirring rate at 150rpm until crystal appears, and adding 0.40 percent of surfactant sodium dodecyl sulfate (based on the mass of the o-vanillin-water mixed solution). Continuously stirring for 5h to enable the crystals to be agglomerated into compact spheres;
(3) vacuum filtering, washing with water, and drying at 35 deg.C under normal pressure for 48 hr to obtain spherical o-vanillin crystal.
The XRD pattern of the product is shown in figure 1, from which it can be seen that the product is a stable crystal; the average particle size of the spherical particles is 900 micrometers, the angle of repose is 31 degrees, and the tap density is 0.51g/cm3。
The invention discloses and provides a method for preparing o-vanillin spherical crystals, which can be realized by a person skilled in the art by properly changing the links such as liquid-liquid phase separation temperature, o-vanillin concentration, cooling end point temperature, surfactant type and the like by referring to the contents. While the process of the present invention has 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 process and product described herein, as well as other suitable variations and combinations, may be made to implement the techniques of the present invention without departing from the spirit and scope of the invention. It is expressly intended that all such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and content of the invention.
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